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10,300 | 28,194,720 | Conclusion Based on current scientific literature , RSH induces greater improvement for mean repeated-sprint performance during sea-level repeated sprinting than RSN . | Background Repeated-sprint training in hypoxia ( RSH ) is a recent intervention regarding which numerous studies have reported effects on sea-level physical performance outcomes that are debated .
No previous study has performed a meta- analysis of the effects of RSH . | The principal objective of this study was to test the hypothesis that acclimatization to moderate altitude ( 2,500 m ) plus training at low altitude ( 1,250 m ) , " living high-training low , " improves sea-level performance in well-trained runners more than an equivalent sea-level or altitude control . Thirty-nine competitive runners ( 27 men , 12 women ) completed 1 ) a 2-wk lead-in phase , followed by 2 ) 4 wk of supervised training at sea level ; and 3 ) 4 wk of field training camp r and omized to three groups : " high-low " ( n = 13 ) , living at moderate altitude ( 2,500 m ) and training at low altitude ( 1,250 m ) ; " high-high " ( n = 13 ) , living and training at moderate altitude ( 2,500 m ) ; or " low-low " ( n = 13 ) , living and training in a mountain environment at sea level ( 150 m ) . A 5,000-m time trial was the primary measure of performance ; laboratory outcomes included maximal O2 uptake ( VO2 max ) , anaerobic capacity ( accumulated O2 deficit ) , maximal steady state ( MSS ; ventilatory threshold ) , running economy , velocity at VO2 max , and blood compartment volumes . Both altitude groups significantly increased VO2 max ( 5 % ) in direct proportion to an increase in red cell mass volume ( 9 % ; r = 0.37 , P < 0.05 ) , neither of which changed in the control . Five-kilometer time was improved by the field training camp only in the high-low group ( 13.4 + /- 10 s ) , in direct proportion to the increase in VO2 max ( r = 0.65 , P < 0.01 ) . Velocity at VO2 max and MSS also improved only in the high-low group . Four weeks of living high-training low improves sea-level running performance in trained runners due to altitude acclimatization ( increase in red cell mass volume and VO2 max ) and maintenance of sea-level training velocities , most likely accounting for the increase in velocity at VO2 max and MSS To assess the impact of ' top-up ' normoxic or hypoxic repeat-sprint training on sea-level repeat-sprint ability , thirty team sport athletes were r and omly split into three groups , which were matched in running repeat-sprint ability ( RSA ) , cycling RSA and 20 m shuttle run performance . Two groups then performed 15 maximal cycling repeat-sprint training sessions over 5 weeks , in either normoxia ( NORM ) or hypoxia ( HYP ) , while a third group acted as a control ( CON ) . In the post-training cycling RSA test , both NORM ( 13.6 % ; p = 0.0001 , and 8.6 % ; p = 0.001 ) and HYP ( 10.3 % ; p = 0.007 , and 4.7 % ; p = 0.046 ) significantly improved overall mean and peak power output , respectively , whereas CON did not change ( 1.4 % ; p = 0.528 , and -1.1 % ; p = 0.571 , respectively ) ; with only NORM demonstrating a moderate effect for improved mean and peak power output compared to CON . Running RSA demonstrated no significant between group differences ; however , the mean sprint times improved significantly from pre- to post-training for CON ( 1.1 % ) , NORM ( 1.8 % ) , and HYP ( 2.3 % ) . Finally , there were no group differences in 20 m shuttle run performance . In conclusion , ' top-up ' training improved performance in a task-specific activity ( i.e. cycling ) ; however , there was no additional benefit of conducting this ' top-up ' training in hypoxia , since cycle RSA improved similarly in both HYP and NORM conditions . Regardless , the ' top-up ' training had no significant impact on running RSA , therefore the use of cycle repeat-sprint training should be discouraged for team sport athletes due to limitations in specificity . Key points'Top-up ' repeat-sprint training performed on a cycle ergometer enhances cycle repeat-sprint ability compared to team sport training only in football players . The addition of moderate hypoxia to repeat-sprint training provides no additional performance benefits to sea-level repeat-sprint ability or endurance performance than normoxic repeat-sprint training.'Top-up ' cycling repeat-sprint training provides no significant additional benefit to running RSA or endurance performance than team sport training only , and therefore running based repeat-sprint interventions are recommended for team sport athletes The purpose s of the present study were to investigate if a ) shuttle-run sprint training performed in a normobaric hypoxia chamber of limited size ( 4.75x2.25 m ) is feasible , in terms of producing the same absolute training load , when compared to training in normoxia , and b ) if such training improves the repeated sprint ability ( RSA ) and the Yo-Yo intermittent recovery ( YYIR ) test outcome in young elite soccer players . Players of an elite soccer training Centre ( age : 15.3 ± 0.5 years , height : 1.73 ± 0.07 m , body mass : 62.6 ± 6.6 kg ) were r and omly assigned to a hypoxia or a normoxia training group . Within a 5-week period , players , who were not informed about the hypoxia intervention , performed at least 7 sessions of identical shuttle-run sprint training either in a normal training room ( FiO2 = 20.95 % ) or in a hypoxic chamber ( FiO2 = 14.8 % ; approximately 3300 m ) , both equipped with the same floor . Each training session comprised 3 series of 5x10s back and forth sprints ( 4.5 m ) performed at maximal intensity . Recovery time between repetitions was 20s and between series 5min . Before and after the training period the RSA ( 6 x 40 m shuttle sprint with 20 s rest between shuttles ) and the YYIR test were performed . The size of the chamber did not restrict the training intensity of the sprint training ( both groups performed approximately 8 shuttles during 10s ) . Training in hypoxia result ed in a lower fatigue slope which indicates better running speed maintenance during the RSA test ( p = 0.024 ) . YYIR performance increased over time ( p = 0.045 ) without differences between groups ( p > 0.05 ) . This study showed that training intensity of the shuttle-run sprint training was not restricted in a hypoxic chamber of limited size which indicates that such training is feasible . Furthermore , hypoxia compared to normoxia training reduced the fatigue slope during the RSA test in youth soccer players . Key PointsShuttle-run sprint training is feasible in hypoxic chambers of limited size ( i.e. , 4.75x2.25m).Hypoxia sprint training ( RSH ) , in comparison to normoxia training , might lead to better running speed maintenance during the repeated sprint ability test PURPOSE The purpose of this study was to assess research aim ed at measuring performance enhancements that affect success of individual elite athletes in competitive events . ANALYSIS Simulations show that the smallest worthwhile enhancement of performance for an athlete in an international event is 0.7 - 0.4 of the typical within-athlete r and om variation in performance between events . Using change in performance in events as the outcome measure in a crossover study , research ers could delimit such enhancements with a sample of 16 - 65 athletes , or with 65 - 260 in a fully controlled study . Sample size for a study using a valid laboratory or field test is proportional to the square of the within-athlete variation in performance in the test relative to the event ; estimates of these variations are therefore crucial and should be determined by repeated- measures analysis of data from reliability studies for the test and event . Enhancements in test and event may differ when factors that affect performance differ between test and event ; overall effects of these factors can be determined with a validity study that combines reliability data for test and event . A test should be used only if it is valid , more reliable than the event , allows estimation of performance enhancement in the event , and if the subjects replicate their usual training and dietary practice s for the study ; otherwise the event itself provides the only dependable estimate of performance enhancement . Publication of enhancement as a percent change with confidence limits along with an analysis for individual differences will make the study more applicable to athletes . Outcomes can be generalized only to athletes with abilities and practice s represented in the study . CONCLUSION estimates of enhancement of performance in laboratory or field tests in most previous studies may not apply to elite athletes in competitive events This study aim ed to determine changes in spring-mass model ( SMM ) characteristics , plantar pressures , and muscle activity induced by the repetition of sprints in soccer-specific conditions ; i.e. , on natural grass with soccer shoes . Thirteen soccer players performed 6 × 20 m sprints interspersed with 20 s of passive recovery . Plantar pressure distribution was recorded via an insole pressure recorder device divided into nine areas for analysis . Stride temporal parameters allowed to estimate SMM characteristics . Surface electromyographic activity was monitored for vastus lateralis , rectus femoris , and biceps femoris muscles . Sprint time , contact time , and total stride duration lengthened from the first to the last repetition ( + 6.7 , + 12.9 , and + 9.3 % ; all P < 0.05 ) , while flight time , swing time , and stride length remained constant . Stride frequency decrease across repetitions approached significance ( −6.8 % ; P = 0.07 ) . No main effect of the sprint number or any significant interaction between sprint number and foot region was found for maximal force , mean force , peak pressure and mean pressure ( all P > 0.05 ) . Center of mass vertical displacement increased ( P < 0.01 ) with time , together with unchanged ( both P > 0.05 ) peak vertical force and leg compression . Vertical stiffness decreased ( −15.9 % ; P < 0.05 ) across trials , whereas leg stiffness changes were not significant ( −5.9 % ; P > 0.05 ) . Changes in root mean square activity of the three tested muscles over sprint repetitions were not significant . Although repeated sprinting on natural grass with players wearing soccer boots impairs their leg-spring behavior ( vertical stiffness ) , there is no substantial concomitant alterations in muscle activation levels or plantar pressure patterns Blood flow to dynamically contracting myocytes is regulated to match O(2 ) delivery to metabolic dem and . The red blood cell ( RBC ) itself functions as an O(2 ) sensor , contributing to the control of O(2 ) delivery by releasing the vasodilators ATP and S-nitrosohaemoglobin with the offloading of O(2 ) from the haemoglobin molecule . Whether RBC number is sensed remains unknown . To investigate the role of RBC number , in isolation and in combination with alterations in blood oxygenation , on muscle and systemic perfusion , we measured local and central haemodynamics during one-legged knee-extensor exercise ( approximately 50 % peak power ) in 10 healthy males under conditions of normocythaemia ( control ) , anaemia , anaemia + plasma volume expansion ( PVX ) , anaemia + PVX + hypoxia , polycythaemia , polycythaemia + hyperoxia and polycythaemia + hypoxia , which changed either RBC count alone or both RBC count and oxyhaemoglobin . Leg blood flow ( LBF ) , cardiac output ( Q ) and vascular conductance did not change with either anaemia or polycythaemia alone . However , LBF increased with anaemia + PVX ( 28 + /- 4 % ) and anaemia + PVX + hypoxia ( 46 + /- 6 % ) and decreased with polycythaemia + hyperoxia ( 18 + /- 5 % ) . LBF and Q with anaemia + PVX + hypoxia ( 8.0 + /- 0.5 and 15.8 + /- 0.7 l min(-1 ) , respectively ) equalled those during maximal knee-extensor exercise . Collectively , LBF and vascular conductance were intimately related to leg arterial-venous ( a-v ) O(2 ) difference ( r(2)= 0.89 - 0.93 ; P < 0.001 ) , suggesting a pivotal role of blood O(2 ) gradients in muscle microcirculatory control . The systemic circulation accommo date d to the changes in muscle perfusion . Our results indicate that , when coping with severe haematological challenges , local regulation of skeletal muscle blood flow and O(2 ) delivery primarily senses alterations in the oxygenation state of haemoglobin and , to a lesser extent , alterations in the number of RBCs and haemoglobin molecules |
10,301 | 31,922,027 | Severe hypoglycaemia was rare not increased for any comparisons .
Conclusions Metformin and the simultaneous initiation of dual therapy , but not AHA used alone or as single add-on combination therapy , was associated with an increased risk of any hypoglycaemia relative to placebo | Objectives For patients with type 2 diabetes , newer antihyperglycaemic agents ( AHA ) , including the dipeptidyl peptidase IV inhibitors ( DPP4i ) , glucagon-like peptide-1 receptor agonists ( GLP1RA ) and sodium glucose co-transporter 2 inhibitors ( SGLT2i ) offer a lower risk of hypoglycaemia relative to sulfonylurea or insulin .
However , it is not clear how AHA compare to placebo on risk of any hypoglycaemia .
This study evaluates the risk of any and severe hypoglycaemia with AHA and metformin relative to placebo . | 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 OBJECTIVE To evaluate the effects of canagliflozin , a sodium-glucose cotransporter 2 inhibitor , in type 2 diabetes mellitus inadequately controlled with metformin monotherapy . RESEARCH DESIGN AND METHODS This was a double-blind , placebo-controlled , parallel-group , multicenter , dose-ranging study in 451 subjects r and omized to canagliflozin 50 , 100 , 200 , or 300 mg once daily ( QD ) or 300 mg twice daily ( BID ) , sitagliptin 100 mg QD , or placebo . Primary end point was change in A1C from baseline through week 12 . Secondary end points included change in fasting plasma glucose ( FPG ) , body weight , and overnight urinary glucose-to-creatinine ratio . Safety and tolerability were also assessed . RESULTS Canagliflozin was associated with significant reductions in A1C from baseline ( 7.6–8.0 % ) to week 12 : −0.79 , −0.76 , −0.70 , −0.92 , and −0.95 % for canagliflozin 50 , 100 , 200 , 300 mg QD and 300 mg BID , respectively , versus −0.22 % for placebo ( all P < 0.001 ) and −0.74 % for sitagliptin . FPG was reduced by −16 to −27 mg/dL , and body weight was reduced by −2.3 to −3.4 % , with significant increases in urinary glucose-to-creatinine ratio . Adverse events were transient , mild to moderate , and balanced across arms except for a non – dose-dependent increase in symptomatic genital infections with canagliflozin ( 3–8 % ) versus placebo and sitagliptin ( 2 % ) . Urinary tract infections were reported without dose dependency in 3–9 % of canagliflozin , 6 % of placebo , and 2 % of sitagliptin arms . Overall incidence of hypoglycemia was low . CONCLUSIONS Canagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss . The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females CONTEXT Dapagliflozin , a selective sodium-glucose cotransporter 2 ( SGLT2 ) inhibitor , reduces hyperglycemia in patients with type 2 diabetes mellitus ( T2DM ) by increasing urinary glucose excretion , and weight loss is a consistent associated finding . OBJECTIVES Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components . DESIGN AND SETTING This was a 24-wk , international , multicenter , r and omized , parallel-group , double-blind , placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries . PATIENTS Included were 182 patients with T2DM ( mean values : women 63.3 and men 58.6 yr of age ; hemoglobin A1c 7.17 % , body mass index 31.9 kg/m2 , and body weight 91.5 kg ) inadequately controlled on metformin . INTERVENTION Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk . MAIN OUTCOME MEASURES Primary endpoint was total body weight ( TBW ) change from baseline at wk 24 . Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass ( FM ) changes from baseline at wk 24 , and patient proportion achieving body weight reduction of at least 5 % at wk 24 . In a subset of patients , magnetic resonance assessment of visceral adipose tissue ( VAT ) and sc adipose tissue ( SAT ) volume and hepatic lipid content were also evaluated . RESULTS At wk 24 , placebo-corrected changes with dapagliflozin were as follows : TBW , -2.08 kg [ 95 % confidence interval (CI)=-2.84 to -1.31 ; P<0.0001 ] ; waist circumference , -1.52 cm ( 95 % CI=-2.74 to -0.31 ; P=0.0143 ) ; FM , -1.48 kg ( 95 % CI=-2.22 to -0.74 ; P=0.0001 ) ; proportion of patients achieving weight reduction of at least 5 % , + 26.2 % ( 95 % CI=15.5 to 36.7 ; P<0.0001 ) ; VAT , -258.4 cm3 ( 95 % CI=-448.1 to -68.6 ; nominal P=0.0084 ) ; SAT , -184.9 cm3 ( 95 % CI=-359.7 to -10.1 ; nominal P=0.0385 ) . In the dapagliflozin vs. placebo groups , respectively , serious adverse events were reported in 6.6 vs. 1.1 % ; events suggestive of vulvovaginitis , balanitis , and related genital infection in 3.3 vs. 0 % ; and lower urinary tract infections in 6.6 vs. 2.2 % . CONCLUSIONS Dapagliflozin reduces TBW , predominantly by reducing FM , VAT and SAT in T2DM inadequately controlled with metformin OBJECTIVE To examine the efficacy and safety of lixisenatide ( 20 μg once daily , administered before the morning or evening meal ) as add-on therapy in patients with type 2 diabetes insufficiently controlled with metformin alone . RESEARCH DESIGN AND METHODS This was a 24-week , r and omized , double-blind , placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes ( HbA1c 7–10 % [ 53−86 mmol/mol ] ) . Patients were r and omized to lixisenatide morning ( n = 255 ) , lixisenatide evening ( n = 255 ) , placebo morning ( n = 85 ) , or placebo evening ( n = 85 ) injections . RESULTS Lixisenatide morning injection significantly reduced mean HbA1c versus combined placebo ( mean change −0.9 % [ 9.8 mmol/mol ] vs. −0.4 % [ 4.4 mmol/mol ] ; least squares [ LS ] mean difference vs. placebo −0.5 % [ 5.5 mmol/mol ] , P < 0.0001 ) . HbA1c was significantly reduced by lixisenatide evening injection ( mean change –0.8 % [ 8.7 mmol/mol ] vs. –0.4 % [ 4.4 mmol/mol ] ; LS mean difference –0.4 % [ 4.4 mmol/mol ] , P < 0.0001 ) . Lixisenatide morning injection significantly reduced 2-h postpr and ial glucose versus morning placebo ( mean change −5.9 vs. −1.4 mmol/L ; LS mean difference −4.5 mmol/L , P < 0.0001 ) . LS mean difference in fasting plasma glucose was significant in both morning ( –0.9 mmol/L , P < 0.0001 ) and evening ( –0.6 mmol/L , P = 0.0046 ) groups versus placebo . Mean body weight decreased to a similar extent in all groups . Rates of adverse events were 69.4 % in both lixisenatide groups and 60.0 % in the placebo group . Rates for nausea and vomiting were 22.7 and 9.4 % for lixisenatide morning and 21.2 and 13.3 % for lixisenatide evening versus 7.6 and 2.9 % for placebo , respectively . Symptomatic hypoglycemia occurred in 6 , 13 , and 1 patient for lixisenatide morning , evening , and placebo , respectively , with no severe episodes . CONCLUSIONS In patients with type 2 diabetes inadequately controlled on metformin , lixisenatide 20 μg once daily administered in the morning or evening significantly improved glycemic control , with a pronounced postpr and ial effect , and was well tolerated UNLABELLED Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones , improving glycemic control in subjects with type 2 diabetes . This twelve-week r and omized , double-masked , placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor , vildagliptin ( 25 mg , bid , n=70 ) VS . placebo ( bid , n=28 ) in previously diet-treated subjects with type 2 diabetes . St and ardized meal tests were performed at baseline and endpoint . The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 + /- 0.2 % ( p=0.0012 ) for the whole cohort ( baseline 8.0 % ) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 % . Fasting glucose and mean pr and ial glucose were reduced by 1.1 + /- 0.4 ( p=0.0043 ) and 1.9 + /- 0.5 mmol/l ( p < 0.0001 ) , respectively . The between-group differences in corrected insulin response at peak glucose and mean pr and ial C-peptide were + 0.06 + /- 0.02 ( p=0.0258 ) and + 0.10 + /- 0.03 nmol/l ( p=0.0031 ) , respectively . Vildagliptin had no effect on fasting lipid levels or body weight . The incidence of adverse events was similar in subjects receiving placebo ( 71.4 % ) and vildagliptin ( 55.7 % ) . CONCLUSION monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes . Concomitant improvements in beta-cell function were also observed . Subjects with higher baseline HbA1c levels showed greater response OBJECTIVE Dapagliflozin , a highly selective inhibitor of the renal sodium-glucose cotransporter-2 , increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner . We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes . RESEARCH DESIGN AND METHODS This was a 24-week parallel-group , double-blind , placebo-controlled phase 3 trial . Patients with A1C 7.0–10 % ( n = 485 ) were r and omly assigned to one of seven arms to receive once-daily placebo or 2.5 , 5 , or 10 mg dapagliflozin once daily in the morning ( main cohort ) or evening ( exploratory cohort ) . Patients with A1C 10.1–12 % ( high-A1C exploratory cohort ; n = 73 ) were r and omly assigned 1:1 to receive blinded treatment with a morning dose of 5 or 10 mg/day dapagliflozin . The primary end point was change from baseline in A1C in the main cohort , statistically tested using an ANCOVA . RESULTS In the main cohort , mean A1C changes from baseline at week 24 were −0.23 % with placebo and −0.58 , −0.77 ( P = 0.0005 vs. placebo ) , and −0.89 % ( P < 0.0001 vs. placebo ) with 2.5 , 5 , and 10 mg dapagliflozin , respectively . Signs , symptoms , and other reports suggestive of urinary tract infections and genital infection were more frequently noted in the dapagliflozin arms . There were no major episodes of hypoglycemia . Data from exploratory cohorts were consistent with these results . CONCLUSIONS Dapagliflozin lowered hyperglycemia in treatment-naive patients with newly diagnosed type 2 diabetes . The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes 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 AIM We evaluated the efficacy and safety of ertugliflozin , an SGLT2 inhibitor , in type 2 diabetes mellitus ( T2DM ) inadequately controlled ( HbA1c , 7.0%-10.5 % ) with metformin monotherapy ( ≥1500 mg/d for ≥8 weeks ) . METHODS This was a double-blind , 26-week , multicentre study with ongoing 78-week extension ( Clinical Trials.gov identifier : NCT02033889 ) . A total of 621 participants were r and omized 1:1:1 to placebo , or ertugliflozin 5 or 15 mg/d . The primary endpoint was change from baseline at week 26 in HbA1c . Secondary efficacy endpoints were change from baseline at week 26 in fasting plasma glucose ( FPG ) , body weight , systolic/diastolic blood pressure ( SBP/DBP ) and number of participants with HbA1c < 7.0 % ( 53 mmol/mol ) . Pre-specified adverse events ( AEs ) of special interest and percent change from baseline in bone mineral density ( BMD ) were also assessed at week 26 . RESULTS At week 26 , the placebo-adjusted least-squares mean change from baseline HbA1c ( 8.1 % ) was -0.7 % and -0.9 % for ertugliflozin 5 and 15 mg , respectively ( both P < .001 ) , to final means of 7.3 % and 7.2 % , respectively . The odds of HbA1c < 7.0 % were significantly greater in both ertugliflozin groups vs placebo . Ertugliflozin significantly reduced FPG , body weight , SBP and DBP vs placebo . The incidence of genital mycotic infections was higher in the ertugliflozin groups ( female subjects : placebo , 0.9 % ; ertugliflozin 5 mg , 5.5 % ; ertugliflozin 15 mg , 6.3 % [ P = .032 ] ; male subjects : 0 % ; 3.1 % ; 3.2 % , respectively ) , as was the incidence of urinary tract infections and symptomatic hypoglycaemia . The incidence of hypovolaemia AEs was similar across groups . Ertugliflozin had no adverse impact on BMD at week 26 . CONCLUSIONS Ertugliflozin added to metformin in patients with inadequately controlled T2DM improved glycaemic control , reduced body weight and BP , but increased the incidence of genital mycotic infections BACKGROUND Glucagon-like peptide-1 ( GLP-1 ) receptor agonists and sodium-glucose co-transporter-2 ( SGLT2 ) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms . We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors , with or without metformin . METHODS AWARD-10 was a phase 3b , double-blind , parallel-arm , placebo-controlled , 24-week study done at 40 clinical sites in Austria , Czech Republic , Germany , Hungary , Israel , Mexico , Spain , and the USA . Eligible adult patients ( ≥18 years ) with inadequately controlled type 2 diabetes ( HbA1c concentration ≥7·0 % [ 53 mmol/mol ] and ≤9·5 % [ 80 mmol/mol ] ) , a BMI of 45 kg/m2 or less , and taking stable doses ( > 3 months ) of an SGLT2 inhibitor ( with or without metformin ) were r and omly assigned ( 1:1:1 ) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg , dulaglutide 0·75 mg , or placebo once per week for 24 weeks . Patients and investigators were masked to dulaglutide and placebo assignment , and those assessing outcomes were masked to study drug assignment . The primary objective was to test for the superiority of dulaglutide ( 1·5 mg or 0·75 mg ) versus placebo for change in HbA1c concentration from baseline at 24 weeks . All analyses were done in the intention-to-treat population , defined as all r and omly assigned patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT02597049 . FINDINGS Between Dec 7 , 2015 , and Feb 3 , 2017 , 424 patients were r and omly assigned to dulaglutide 1·5 mg ( n=142 ) , dulaglutide 0·75 mg ( n=142 ) , and placebo ( n=140 ) . One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug . The reduction in HbA1c concentration at 24 weeks was larger in patients receiving dulaglutide ( least squares mean [ LSM ] for dulaglutide 1·5 mg -1·34 % [ SE 0·06 ] or -14·7 mmol/mol [ 0·6 ] ; dulaglutide 0·75 mg -1·21 % [ 0·06 ] or -13·2 mmol/mol [ 0·6 ] ) than in patients receiving placebo ( -0·54 % [ 0·06 ] or -5·9 mmol/mol [ 0·6 ] ; p<0·0001 for both groups vs placebo ) . The LSM differences were -0·79 % ( 95 % CI -0·97 to -0·61 ) or -8·6 mmol/mol ( -10·6 to -6·7 ) for dulaglutide 1·5 mg and -0·66 % ( -0·84 to -0·49 ) or -7·2 mmol/mol ( -9·2 to -5·4 ) for dulaglutide 0·75 mg ( p<0·0001 for both ) . Serious adverse events were reported for five ( 4 % ) patients in the dulaglutide 1·5 mg group , three ( 2 % ) patients in the dulaglutide 0·75 mg group , and five ( 4 % ) patients in the placebo group . Treatment-emergent adverse events were more common in patients treated with dulaglutide than in patients who received placebo , mainly because of an increased incidence of gastrointestinal adverse events . Nausea ( 21 [ 15 % ] patients in the dulaglutide 1·5 mg group vs seven [ 5 % ] in the dulaglutide 0·75 mg group vs five [ 4 % ] in the placebo group ) , diarrhoea ( eight [ 6 % ] vs 14 [ 10 % ] vs four [ 3 % ] ) , and vomiting ( five [ 4 % ] vs four [ 3 % ] vs one [ 1 % ] ) were more common with dulaglutide than with placebo . One episode of severe hypoglycaemia was reported in the dulaglutide 0·75 mg group . Two ( 1 % ) patients receiving dulaglutide 1·5 mg died , but these deaths were not considered to be related to study drug ; no deaths occurred in the other groups . INTERPRETATION Dulaglutide as add-on treatment to SGLT2 inhibitors ( with or without metformin ) result ed in significant and clinical ly relevant improvements in glycaemic control , with acceptable tolerability that is consistent with the established safety profile of dulaglutide . FUNDING Eli Lilly and Company Importance Glucagon-like peptide-1 ( GLP-1 ) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection . Objectives To compare the effects of oral semaglutide with placebo ( primary ) and open-label subcutaneous semaglutide ( secondary ) on glycemic control in patients with type 2 diabetes . Design , Setting , and Patients Phase 2 , r and omized , parallel-group , dosage-finding , 26-week trial with 5-week follow-up at 100 sites ( hospital clinics , general practice s , and clinical research centers ) in 14 countries conducted between December 2013 and December 2014 . Of 1106 participants assessed , 632 with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were r and omized . R and omization was stratified by metformin use . Interventions Once-daily oral semaglutide of 2.5 mg ( n = 70 ) , 5 mg ( n = 70 ) , 10 mg ( n = 70 ) , 20 mg ( n = 70 ) , 40-mg 4-week dose escalation ( st and ard escalation ; n = 71 ) , 40-mg 8-week dose escalation ( slow escalation ; n = 70 ) , 40-mg 2-week dose escalation ( fast escalation , n = 70 ) , oral placebo ( n = 71 ; double-blind ) or once-weekly subcutaneous semaglutide of 1.0 mg ( n = 70 ) for 26 weeks . Main Outcomes and Measures The primary end point was change in hemoglobing A1c ( HbA1c ) from baseline to week 26 . Secondary end points included change from baseline in body weight and adverse events . Results Baseline characteristics were comparable across treatment groups . Of the 632 r and omized patients ( mean age , 57.1 years [ SD , 10.6 ] ; men , 395 ( 62.7 % ) ; diabetes duration , 6.3 years [ SD , 5.2 ] ; body weight , 92.3 kg [ SD , 16.8 ] ; BMI , 31.7 [ SD , 4.3 ] ) , 583 ( 92 % ) completed the trial . Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide ( dosage-dependent range , −0.7 % to −1.9 % ) and subcutaneous semaglutide ( −1.9 % ) and placebo ( −0.3 % ) ; oral semaglutide reductions were significant vs placebo ( dosage-dependent estimated treatment difference [ ETD ] range for oral semaglutide vs placebo , –0.4 % to –1.6 % ; P = .01 for 2.5 mg , < .001 for all other dosages ) . Reductions in body weight were greater with oral semaglutide ( dosage-dependent range , −2.1 kg to −6.9 kg ) and subcutaneous semaglutide ( −6.4 kg ) vs placebo ( −1.2 kg ) , and significant for oral semaglutide dosages of 10 mg or more vs placebo ( dosage-dependent ETD range , –0.9 to –5.7 kg ; P < .001 ) . Adverse events were reported by 63 % to 86 % ( 371 of 490 patients ) in the oral semaglutide groups , 81 % ( 56 of 69 patients ) in the subcutaneous semaglutide group , and 68 % ( 48 of 71 patients ) in the placebo group ; mild to moderate gastrointestinal events were most common . Conclusions and Relevance Among patients with type 2 diabetes , oral semaglutide result ed in better glycemic control than placebo over 26 weeks . These findings support phase 3 studies to assess longer-term and clinical outcomes , as well as safety . Trial Registration clinical trials.gov Identifier : 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 ) Aims : This study evaluated the efficacy and safety of teneligliptin in patients with inadequately controlled type 2 diabetes mellitus ( T2DM ) . Setting s and Design : This was a r and omized , doubleblind , placebocontrolled , parallelgroup , multicenter , Phase III study . Subjects and Methods : Patients with T2DM and inadequate glycemic control ( glycosylated hemoglobin [ HbA1c ] : > 7.0-≤8.5 % ) were enrolled . Patients were r and omly assigned ( ratio : 2:1 ) to receive teneligliptin 20 mg ( Glenmark ) or placebo . The primary efficacy variable was change from baseline in HbA1c at week 16 . Additional analyses included the proportion of patients who achieved target of HbA1c ≤7.0 % , changes in fasting plasma glucose ( FPG ) , and postpr and ial glucose ( PPG ) . Statistical Analysis : Mean change in HbA1c was analyzed using an analysis of covariance model , least square ( LS ) means , 95 % confidence intervals ( CIs ) , and P values were calculated . Results : Overall , 237 patients were included . Patients of the teneligliptin group showed reduced HbA1c levels ( LS mean difference = −0.304 % for intent-to-treat [ ITT ] ; −0.291 % for per- protocol ( PP ) population s ) after 16 weeks of treatment , and a statistically significant difference was observed between the ITT ( LS mean difference = 0.555 ; 95 % CI : 0.176–0.934 ; P = 0.0043 ) and PP population s ( LS mean difference = 0.642 ; 95 % CI : 0.233–1.052 ; P = 0.0023 ) . Target HbA1c level was achieved by a greater proportion of teneligliptin group patients ( ITT , 43.4 % ; PP , 43.6 % ) than placebo group patients ( ITT , 27.3 % ; PP , 26.6 % ) . Reduction in FPG levels was observed in ITT ( LS mean difference : 8.829 ; 95 % CI : −4.357–22.016 ; P = 0.1883 ) and PP population s ( LS mean difference : 11.710 mg/dL ; 95 % CI : −2.893 - 26.312 ; P = 0.1154 ) . Reduction in PPG levels was higher in teneligliptin group than placebo group in both ITT ( LS mean difference = 25.849 mg/dL ; 95 % CI : 7.143–44.556 ; P = 0.0070 ) and PP population s ( LS mean difference = 25.683 mg/dL ; 95 % CI : 5.830–45.536 ; P = 0.0115 ) . Overall , 44 patients ( 18.6 % ) experienced at least one adverse event . Three or more hypoglycemic events were experienced by 2.5 % patients of teneligliptin group and none in placebo group . Conclusion : Treatment with once-daily teneligliptin led to statistically significant and clinical ly meaningful reductions in HbA1c and PPG , and was well tolerated in Indian patients with T2DM AIMS To assess the efficacy and safety of once-weekly omarigliptin as monotherapy in people with type 2 diabetes mellitus ( T2DM ) . METHODS People with T2DM not on glucose-lowering medications , or who were washed off monotherapy or low-dose dual therapy , were r and omized double-blind to omarigliptin 25 mg ( n=165 ) or matching omarigliptin placebo ( n=164 ) for 24 weeks , followed by a 30-week period to assess continuing efficacy and safety longer-term of omarigliptin during which metformin was added to the placebo group and metformin placebo to the omarigliptin group . RESULTS From a mean baseline HbA1c of 8.0 - 8.1 % , the least squares mean ( 95 % CI ) change from baseline in HbA1c at week 24 ( primary endpoint ) was -0.49 % ( -0.73 , -0.24 ) in the omarigliptin group and -0.10 % ( -0.34 , 0.14 ) in the placebo group , for a between-group difference of -0.39 % ( -0.59 , -0.19 ) ( p<.001 ) . Protocol deviation in use of metformin by 38 of 252 ( 15 % ) people whose sample s were available for evaluation probably attenuated glycemic efficacy results , as suggested by the LS mean difference -0.53 % ( -0.75 , -0.32 ) after censoring of such participants . At 24 and 54 weeks , the incidences of adverse events ( AEs ) were similar in the omarigliptin and placebo groups . During 54 weeks there were no AEs of symptomatic hypoglycemia in the omarigliptin group and 5 AEs in the placebo group . Over 54 weeks , a majority of the omarigliptin treatment had a persistent reduction in HbA1c , remaining rescue-free . CONCLUSIONS In people with T2DM , omarigliptin monotherapy improved glycemic control over 54 weeks and was generally well tolerated with a low risk of hypoglycemia . Clinical Trials.gov Identifier : NCT01717313 . EudraCT Number : 2012 - 003626 - 24 Abstract Objective : To examine the efficacy and safety of the once-weekly ( q.w . ) dipeptidyl peptidase-4 inhibitor , omarigliptin , in patients with type 2 diabetes ( T2DM ) and inadequate glycemic control on metformin monotherapy . Methods : In a r and omized , double-blind trial , patients with T2DM on a stable dose of metformin monotherapy ( ≥1500 mg/day ) with glycated hemoglobin ( HbA1c ) of 7.0–10.5 % were r and omized to omarigliptin 25 mg q.w . or matching placebo ( n = 201 in both ) for 24 weeks ( primary timepoint ) followed by an additional 80-week treatment period . Results : At week 24 , from a mean baseline HbA1c of 8.0–8.1 % , the least squares ( LS ) mean ( 95 % CI ) change from baseline in HbA1c ( primary end-point ) was –0.54 % ( –0.69 % , –0.40 % ) in the omarigliptin group and 0.00 % ( –0.14 % , 0.15 % ) in the placebo group , for a between-group difference of –0.55 % ( –0.75 % , –0.34 % ) ; p < .001 . Between-group differences ( LS mean 95 % CI ) for the secondary end-points of 2-h post-meal glucose and fasting plasma glucose ( omarigliptin vs placebo ) were –0.8 mmol/L ( –1.4 , –0.2 ) ( p = .011 ) and –0.5 mmol/L ( –0.9 , –0.1 ) ( p = .010 ) , respectively . At week 24 , the incidences of symptomatic hypoglycemia and subjects with one or more adverse event ( AE ) , serious AEs , and discontinuations due to an AE were similar in the omarigliptin and placebo groups . Over 104 weeks , omarigliptin treatment provided a clinical ly meaningful reduction in HbA1c . Conclusions : In patients with T2DM , adding omarigliptin 25 mg q.w . to metformin monotherapy improved glycemic control over 104 weeks and was generally welltolerated with a low risk of hypoglycemia BACKGROUND Despite a broad range of pharmacological options for the treatment of type 2 diabetes , optimum glycaemic control remains challenging for many patients and new therapies are necessary . Semaglutide is a glucagon-like peptide-1 ( GLP-1 ) analogue in phase 3 development for type 2 diabetes . We assessed the efficacy , safety , and tolerability of semaglutide monotherapy , compared with placebo , in treatment-naive patients with type 2 diabetes who had insufficient glycaemic control with diet and exercise alone . METHODS We did a double-blind , r and omised , parallel-group , international , placebo-controlled phase 3a trial ( SUSTAIN 1 ) at 72 sites in Canada , Italy , Japan , Mexico , Russia , South Africa , UK , and USA ( including hospitals , clinical research units , and private offices ) . Eligible participants were treatment-naive individuals aged 18 years or older with type 2 diabetes treated with only diet and exercise alone for at least 30 days before screening , with a baseline HbA1c of 7·0%-10·0 % ( 53 - 86 mmol/mol ) . We r and omly assigned participants ( 2:2:1:1 ) to either once-weekly subcutaneously injected semaglutide ( 0·5 mg or 1·0 mg ) , or volume-matched placebo ( 0·5 mg or 1·0 mg ) , for 30 weeks via prefilled PDS290 pen-injectors . Participants did their own injections and were encouraged to administer them on the same day of each week in the same area of their body ; the time of day and proximity of meal times was not specified . We did the r and omisation with an interactive voice or web response system . Investigators , participants , and the funder of the study remained masked throughout the trial . The primary endpoint was the change in mean HbA1c from baseline to week 30 , and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30 . We assessed efficacy and safety in the modified intention-to-treat population ( ie , all participants who were exposed to at least one dose of study drug ) ; both placebo groups were pooled for assessment . This trial was registered with Clinical Trials.gov , number NCT02054897 . FINDINGS Between February 3 , 2014 , and August 21 , 2014 , we r and omly assigned 388 participants to treatment ; 387 received at least one dose of study medication ( 128 0·5 mg semaglutide , 130 1·0 mg semaglutide , 129 placebo ) . 17 ( 13 % ) of those assigned to 0·5 mg semaglutide , 16 ( 12 % ) assigned to 1·0 mg semaglutide , and 14 ( 11 % ) assigned to placebo discontinued treatment ; the main reason for discontinuation was gastrointestinal adverse events such as nausea . Mean baseline HbA1c was 8·05 % ( SD 0·85 ) ; at week 30 , HbA1c significantly decreased by 1·45 % ( 95 % CI -1·65 to -1·26 ) with 0·5 mg semaglutide ( estimated treatment difference vs placebo -1·43 % , 95 % CI -1·71 to -1·15 ; p<0·0001 ) , significantly decreased by 1·55 % ( -1·74 to -1·36 ) with 1·0 mg semaglutide ( estimated treatment difference vs placebo -1·53 % , -1·81 to -1·25 ; p<0·0001 ) , and non-significantly decreased by 0·02 % ( -0·23 to 0·18 ) with placebo . Mean baseline bodyweight was 91·93 kg ( SD 23·83 ) ; at week 30 , bodyweight significantly decreased by 3·73 kg ( 95 % CI -4·54 to -2·91 ) with 0·5 mg semaglutide ( estimated treatment difference vs placebo -2·75 kg , 95 % CI -3·92 to -1·58 ; p<0·0001 ) , significantly decreased by 4·53 kg ( -5·34 to -3·72 ) with 1·0 mg semaglutide ( estimated treatment difference vs placebo -3·56 kg , -4·74 to -2·38 ; p<0·0001 ) , and non-significantly decreased by 0·98 kg ( -1·82 to -0·13 ) with placebo . No deaths were reported in any of the study groups and most reported adverse events were of mild or moderate severity . The most frequently reported adverse events in both semaglutide groups were gastrointestinal in nature : nausea was reported in 26 ( 20 % ) who received 0·5 mg semaglutide , 31 ( 24 % ) who received 1·0 mg semaglutide , and 10 ( 8 % ) who received placebo , and diarrhoea was reported in 16 ( 13 % ) who received 0·5 mg semaglutide , 14 ( 11 % ) who received 1·0 mg semaglutide , and three ( 2 % ) who received placebo . INTERPRETATION Semaglutide significantly improved HbA1c and bodyweight in patients with type 2 diabetes compared with placebo , and showed a similar safety profile to currently available GLP-1 receptor agonists , representing a potential treatment option for such patients . FUNDING Novo Nordisk A/S , Denmark 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 To conduct a phase III study to evaluate the efficacy and safety of ertugliflozin monotherapy in people with type 2 diabetes OBJECTIVES This study evaluated if triple oral therapy can be useful in improving glycemic control compared with metformin monotherapy and with a metformin and pioglitazone combination . Furthermore , we also compared a triple metformin+pioglitazone+glibenclamide combination with a metformin+pioglitazone+sitagliptin one . SUBJECTS AND METHODS After a 2-year run-in therapy-augmenting phase with metformin and pioglitazone , 453 overweight , type 2 diabetes patients were r and omized to 1 year of sitagliptin versus 1 year of glibenclamide to evaluate , as the primary outcome , the variation of β-cell function both in a fasting state and after an euglycemic hyperinsulinemic and hyperglycemic clamp . As secondary outcomes we evaluated glycemic control and insulin resistance . RESULTS Both the triple therapy combinations were more effective in reducing glycated hemoglobin compared with metformin monotherapy and with dual therapy metformin+pioglitazone . Fasting plasma insulin level and the homeostasis model assessment insulin resistance index were significantly increased by triple therapy with glibenclamide and decreased by the one with sitagliptin . Although sitagliptin did not change the homeostasis model assessment β-function index , this value was significantly increased by glibenclamide . The fasting plasma proinsulin level was decreased by sitagliptin . Triple therapy with sitagliptin greatly improved β-cell function measures compared with the glibenclamide one and also compared with metformin monotherapy and with the metformin+pioglitazone combination . CONCLUSIONS Dual combination therapy is more effective than monotherapy in improving glycemic control . When double therapy is not enough to reach an adequate glycemic control , sitagliptin should be preferred to glibenclamide as the third agent because of its positive effect on β-cells OBJECTIVE To evaluate the efficacy , safety , and tolerability of incremental doses of albiglutide , a long-acting glucagon-like peptide-1 receptor agonist , administered with three dosing schedules in patients with type 2 diabetes inadequately controlled with diet and exercise or metformin monotherapy . RESEARCH DESIGN AND METHODS In this r and omized multicenter double-blind parallel-group study , 356 type 2 diabetic subjects with similar mean baseline characteristics ( age 54 years , diabetes duration 4.9 years , BMI 32.1 kg/m2 , A1C 8.0 % ) received subcutaneous placebo or albiglutide ( weekly [ 4 , 15 , or 30 mg ] , biweekly [ 15 , 30 , or 50 mg ] , or monthly [ 50 or 100 mg ] ) or exenatide twice daily as an open-label active reference ( per labeling in metformin subjects only ) over 16 weeks followed by an 11-week washout period . The main outcome measure was change from baseline A1C of albiglutide groups versus placebo at week 16 . RESULTS Dose-dependent reductions in A1C were observed within all albiglutide schedules . Mean A1C was similarly reduced from baseline by albiglutide 30 mg weekly , 50 mg biweekly ( every 2 weeks ) , and 100 mg monthly ( −0.87 , −0.79 , and −0.87 % , respectively ) versus placebo ( −0.17 % , P < 0.004 ) and exenatide ( −0.54 % ) . Weight loss ( −1.1 to −1.7 kg ) was observed with these three albiglutide doses with no significant between-group effects . The incidence of gastrointestinal adverse events in subjects receiving albiglutide 30 mg weekly was less than that observed for the highest biweekly and monthly doses of albiglutide or exenatide . CONCLUSIONS Weekly albiglutide administration significantly improved glycemic control and elicited weight loss in type 2 diabetic patients , with a favorable safety and tolerability profile 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 Aims We examined the efficacy , safety and tolerability of canagliflozin , a sodium glucose co-transporter 2 inhibitor , in Japanese patients with type 2 diabetes ( T2DM ) undergoing diet and exercise therapy . Methods Patients aged 20–80 years with T2DM diagnosed ≥3 months previously , and HbA1c of 6.9–9.9 % were r and omized to 50 , 100 , 200 or 300 mg canagliflozin or placebo once daily for 12 weeks . The primary and secondary endpoints were changes in HbA1c , fasting plasma glucose ( FPG ) , urinary glucose/creatinine and postpr and ial glycaemic parameters following a meal test . The safety assessment s included adverse events ( AEs ) and clinical laboratory tests . Results Overall , 383 patients were r and omized to receive either placebo ( n = 75 ) , or 50 mg ( n = 82 ) , 100 mg ( n = 74 ) , 200 mg ( n = 77 ) or 300 mg canagliflozin ( n = 75 ) . At week 12 , significant reductions in HbA1c were observed in all canagliflozin groups relative to placebo ( −0.61 , –0.80 , –0.79 and −0.88 % for 50 , 100 , 200 and 300 mg , respectively , versus + 0.11 % for placebo ; all , p < 0.01 ) . FPG and postpr and ial glycaemic parameters improved significantly in the canagliflozin groups . Body weight was significantly decreased by canagliflozin . No deaths or drug-related serious AEs were reported . There was no dose-dependent increase in the incidence of AEs in the canagliflozin groups . The incidence of hypoglycaemia was low ; episodes were not severe or dose dependent . Canagliflozin did not affect serum creatinine levels or the urinary albumin/creatinine ratio . Conclusions Treatment with canagliflozin for 12 weeks significantly improved glycaemic control and reduced body weight in Japanese patients with T2DM . Canagliflozin was well tolerated BACKGROUND In patients with type 2 diabetes , improving adherence to medication is important in order to maintain favourable glycaemic control during long-term treatment and , thus , prevent the onset or aggravation of complications . SYR-472 is a novel once-weekly oral DPP-4 inhibitor for type 2 diabetes , which could be a treatment option when clinicians seek to improve medication adherence by reducing the number of required administrations . In this study , we assessed the efficacy and safety of SYR-472 in patients with type 2 diabetes . METHODS In this phase 2 , multicentre , r and omised , double-blind , parallel-group , placebo-controlled , dose-ranging study , we included Japanese patients with inadequately controlled type 2 diabetes despite diet and exercise treatment . Patients were r and omly assigned ( allocation ratio 1:1:1:1:1:1 ) to receive either placebo or SYR-472 at five different doses ( 12·5 mg , 25 mg , 50 mg , 100 mg , or 200 mg ) . R and omisation was done with a permuted block schedule . All investigators and patients were unaware of the treatment assignment . Treatment drug was given orally once weekly for 12 weeks . The primary efficacy variable was the change in HbA1c concentration from baseline to the end of treatment . This study has been registered at the Japan Pharmaceutical Information Center ( JAPIC ) Clinical Trials Information : Japic CTI-090899 . FINDINGS 322 patients were r and omly assigned to receive placebo ( 55 patients ) or SYR-472 at 12·5 mg ( 54 patients ) , 25 mg ( 52 patients ) , 50 mg ( 51 patients ) , 100 mg ( 55 patients ) or 200 mg ( 55 patients ) . The least square ( LS ) mean change in HbA1c concentration from baseline was 0·35 % ( SE 0·068 ; -20 mmol/mol ) for the placebo group , -0·37 % ( 0·068 ; -28 mmol/mol ) for the 12·5 mg group , -0·32 % ( 0·070 ; -27 mmol/mol ) for the 25 mg group , -0·42 % ( 0·070 ; -28 mmol/mol ) for the 50 mg group , -0·54 % ( 0·068 ; -29 mmol/mol ) for the 100 mg group , and -0·55 % ( 0·069 ; -30 mmol/mol ) for the 200 mg group . In general , HbA1c concentration decreased in a dose-dependent manner ( trend test using contrast coefficients p<0·0001 ) and the reduction was significantly greater for all SYR-472 doses ( p<0·0001 for each group ) than for placebo . The incidence of treatment-emergent adverse events in each SYR-472 group was similar to that in the placebo group . The most common adverse event was nasopharyngitis in all groups . No episodes of hypoglycaemia defined by investigator occurred with any treatment during the study . INTERPRETATION Once-weekly SYR-472 treatment produced clinical ly and statistically significant improvements in glycaemic control in patients with type 2 diabetes . It was well tolerated and might be a new treatment option for patients with this disease . FUNDING Takeda Pharmaceutical Company Limited 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 This study aim ed to evaluate the efficacy and safety of linagliptin ( a novel dipeptidyl peptidase (DPP)-4 inhibitor ) on glucose metabolism and β-cell function in Chinese patients with newly-diagnosed , drug-naïve type 2 diabetes mellitus ( T2DM ) . Material / Methods Newly-diagnosed and drug-naïve T2DM patients were enrolled . After 4-week lifestyle modulation and 2-week placebo run-in , 57 patients were r and omized to double-blind treatment with linagliptin ( n=34 ) or placebo ( n=23 ) . The primary endpoint was the change from baseline in glycosylated hemoglobin A1c ( HbA1c ) after 24 weeks . Fasting plasma glucose ( FPG ) , 2-h postpr and ial plasma glucose ( 2h-PPG ) , fasting insulin , proinsulin-to-insulin ratio , homeostasis model assessment of insulin resistance ( HOMA-IR ) , and homeostasis model assessment of β-cell function ( HOMA-β ) were also evaluated . Results Baseline characteristics were similar between the 2 groups . Compared with placebo , linagliptin therapy result ed in a significant decrease in HbA1C ( −1.2±0.7 % vs. −0.4±0.4 % , P<0.001 ) , FBG ( −0.98±1.17 vs. −0.32±0.51 mmol/L , P=0.011 , and 2h-PPG ( −2.02±0.94 vs. −0.97±0.63 mmol/L , P<0.001 ) . Significant differences were observed for the proinsulin/insulin ratio ( P<0.001 ) and HOMA-β index ( P=0.001 ) . Rates of adverse events were similar between the 2 groups ( 30.3 % vs. 27.3 % ) . All adverse events were mild . One patient discontinued participation due to pregnancy . Conclusions Linagliptin treatment result ed in a significant and clinical ly meaningful improvement of glycemic control in drug-naïve Chinese patients with T2DM , as well as improved parameters of β-cell function . Linagliptin had an excellent safety profile BACKGROUND Dapagliflozin , a highly selective sodium-glucose cotransporter 2 inhibitor , reduces hyperglycemia , body weight , and blood pressure in patients with type 2 diabetes ( T2D ) . METHODS This r and omized double-blind placebo-controlled parallel-group 24-week study assessed the efficacy , safety , and tolerability of dapagliflozin added to metformin in Asian patients with inadequately controlled T2D ( HbA1c 7.5%-10.5 % ) . Patients were r and omized to receive placebo ( n = 145 ) or dapagliflozin 5 ( n = 147 ) or 10 mg ( n = 152 ) . RESULTS Most participants were Chinese ( 86.0 % ) , with a mean age of 53.8 years and mean T2D duration of 4.9 years ; 92.1 % completed the study . Adjusted mean HbA1c changes from baseline at Week 24 ( primary endpoint ) were -0.23 % , -0.82 % , and -0.85 % in the placebo , dapagliflozin 5 and 10 mg groups , respectively , result ing in dapagliflozin 5 and 10 mg versus placebo differences of -0.59 % and -0.62 % , respectively ( both P < 0.0001 ) . Dapagliflozin 5 and 10 mg differences versus placebo were , respectively : -1.2 and -1.5 mmol/L for fasting plasma glucose ; -1.1 and -1.8 kg for weight ; and -2.3 and -2.7 mmol/L for 2-h postpr and ial glucose ( all P < 0.0001 ) . In the placebo , dapagliflozin 5 and 10 mg groups , respectively : adverse events ( AEs ) occurred in 52.4 % , 52.4 % , and 55.3 % of patients ; serious AEs occurred in 4.1 % , 2.0 % , and 2.0 % ; urinary tract infections occurred in 4.8 % , 4.1 % , and 6.6 % ; and genital infections occurred in 0 % , 2.0 % , and 1.3 % . No AEs of pyelonephritis or renal failure occurred . CONCLUSIONS Dapagliflozin 5 or 10 mg as add-on to metformin was well tolerated in Asian patients with T2D and significantly improved glycemic control with the additional benefit of weight reduction OBJECTIVE To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing metformin treatment . RESEARCH DESIGN AND METHODS We conducted a 12-week , r and omized , double-blind , placebo-controlled trial in 107 patients with type 2 diabetes with a 40-week extension in those completing the core study and agreeing , together with the investigator , to extend treatment to 1 year . Placebo ( n=51 ) or LAF237 ( 50 mg once daily , n=56 ) was added to ongoing metformin treatment ( 1,500 - 3,000 mg/day ) . HbA1c and fasting plasma glucose ( FPG ) were measured periodically , and st and ardized meal tests were performed at baseline , week 12 , and week 52 . RESULTS In patients r and omized to LAF237 , baseline HbA1c averaged 7.7 + /- 0.1 % and decreased at week 12 ( Delta=-0.6 + /- 0.1 % ) , whereas HbA1c did not change from a baseline of 7.9 + /- 0.1 % in patients given placebo ( between-group difference in DeltaHbA1c=-0.7 + /- 0.1 % , P < 0.0001 ) . Mean pr and ial glucose and FPG were significantly reduced in patients receiving LAF237 versus placebo by 2.2 + /- 0.4 mmol/l ( P < 0.0001 ) and 1.2 + /- 0.4 mmol/l ( P=0.0057 ) , respectively , but plasma insulin levels were not affected . At end point of the extension , the between-group differences in change in mean pr and ial glucose , insulin , and FPG were -2.4 + /- 0.6 mmol/l ( P=0.0001 ) , 40 + /- 16 pmol/l ( P=0.0153 ) , and -1.1 + /- 0.5 mmol/l ( P=0.0312 ) , respectively . HbA1c did not change from week 12 to week 52 in LAF237-treated patients ( n=42 ) but increased in participants given placebo ( n=29 ) . The between-group difference in DeltaHbA1c after 1 year was -1.1 + /- 0.2 % ( P < 0.0001 ) . CONCLUSIONS Data from this study demonstrate that LAF237 effectively prevents deterioration of glycemic control when added to metformin monotherapy in type 2 diabetes 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 Objectives To investigate potential determinants of severe hypoglycaemia , including baseline characteristics , in the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin ( haemoglobin A1C ) achieved during therapy . Design Post hoc epidemiological analysis of a double 2 × 2 factorial , r and omised , controlled trial . Setting Diabetes clinics , research clinics , and primary care clinics . Participants 10 209 of the 10 251 participants enrolled in the ACCORD study with type 2 diabetes , a haemoglobin A1C concentration of 7.5 % or more during screening , and aged 40 - 79 years with established cardiovascular disease or 55 - 79 years with evidence of significant atherosclerosis , albuminuria , left ventricular hypertrophy , or two or more additional risk factors for cardiovascular disease ( dyslipidaemia , hypertension , current smoker , or obese ) . Interventions Intensive ( haemoglobin A1C < 6.0 % ) or st and ard ( haemoglobin A1C 7.0 - 7.9 % ) glucose control . Main outcome measures Severe hypoglycaemia was defined as episodes of “ low blood glucose ” requiring the assistance of another person and documentation of either a plasma glucose less than 2.8 mmol/l ( < 50 mg/dl ) or symptoms that promptly resolved with oral carbohydrate , intravenous glucose , or glucagon . Results The annual incidence of hypoglycaemia was 3.14 % in the intensive treatment group and 1.03 % in the st and ard glycaemia group . We found significantly increased risks for hypoglycaemia among women ( P=0.0300 ) , African-Americans ( P<0.0001 compared with non-Hispanic whites ) , those with less than a high school education ( P<0.0500 compared with college graduates ) , aged participants ( P<0.0001 per 1 year increase ) , and those who used insulin at trial entry ( P<0.0001 ) . For every 1 % unit decline in the haemoglobin A1C concentration from baseline to 4 month visit , there was a 28 % ( 95 % CI 19 % to 37 % ) and 14 % ( 4 % to 23 % ) reduced risk of hypoglycaemia requiring medical assistance in the st and ard and intensive groups , respectively . In both treatment groups , the risk of hypoglycaemia requiring medical assistance increased with each 1 % unit increment in the average up date d haemoglobin A1C concentration ( st and ard arm : hazard ratio 1.76 , 95 % CI 1.50 to 2.06 ; intensive arm : hazard ratio 1.15 , 95 % CI 1.02 to 1.21 ) . Conclusions A greater drop in haemoglobin A1C concentration from baseline to the 4 month visit was not associated with an increased risk for hypoglycaemia . Patients with poorer glycaemic control had a greater risk of hypoglycaemia , irrespective of treatment group . Identification of baseline subgroups with increased risk for severe hypoglycaemia can provide guidance to clinicians attempting to modify patient therapy on the basis of individual risk . Trial registration Clinical Trials.gov number NCT00000620 BACKGROUND Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus ( NIDDM ) in the United States . Recently , however , metformin has been approved for the treatment of NIDDM . METHODS We performed two large , r and omized , parallel-group , double-blind , controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet ( protocol 1 : metformin vs. placebo ; 289 patients ) , or diet plus glyburide ( protocol 2 : metformin and glyburide vs. metformin vs. glyburide ; 632 patients ) . To determine efficacy we measured plasma glucose ( while the patients were fasting and after the oral administration of glucose ) , lactate , lipids , insulin , and glycosylated hemoglobin before , during , and at the end of the study . RESULTS In protocol 1 , at the end of the study the 143 patients in the metformin group , as compared with the 146 patients in the placebo group , had lower mean ( + /- SE ) fasting plasma glucose concentrations ( 189 + /- 5 vs. 244 + /- 6 mg per deciliter [ 10.6 + /- 0.3 vs. 13.7 + /- 0.3 mmol per liter ] , P < 0.001 ) and glycosylated hemoglobin values ( 7.1 + /- 0.1 percent vs. 8.6 + /- 0.2 percent , P < 0.001 ) . In protocol 2 , the 213 patients given metformin and glyburide , as compared with the 210 patients treated with glyburide alone , had lower mean fasting plasma glucose concentrations ( 187 + /- 4 vs. 261 + /- 4 mg per deciliter [ 10.5 + /- 0.2 vs. 14.6 + /- 0.2 mmol per liter ] , P < 0.001 ) and glycosylated hemoglobin values ( 7.1 + /- 0.1 percent vs. 8.7 + /- 0.1 percent , P < 0.001 ) . The effect of metformin alone was similar to that of glyburide alone . Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia , as compared with 3 percent in the glyburide group and 2 percent in the metformin group . In both protocol s the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations , whereas the values in the respective control groups did not change . There were no significant changes in fasting plasma lactate concentrations in any of the groups . CONCLUSIONS Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone OBJECTIVE To investigate the efficacy and safety of miglitol in combination with metformin in improving glycemic control in out patients in whom type 2 diabetes is insufficiently controlled by diet alone . RESEARCH DESIGN AND METHODS In this multicenter , double-blind , placebo-controlled study , 324 patients with type 2 diabetes were r and omized , after an 8-week placebo run-in period , to treatment with either placebo , miglitol alone , metformin alone , or miglitol plus metformin for 36 weeks . The miglitol was titrated to 100 mg three times a day and metformin was administered at 500 mg three times a day . The primary efficacy criterion was change in HbA(1c ) from baseline to the end of treatment . Secondary parameters included changes in fasting and postpr and ial plasma glucose and insulin levels , serum triglyceride levels , and responder rate . RESULTS A total of 318 patients were valid for intent-to-treat analysis . A reduction in mean placebo-subtracted HbA(1c ) of -1.78 % was observed with miglitol plus metformin combination therapy , which was significantly different from treatment with metformin alone ( -1.25 ; P = 0.002 ) . Miglitol plus metformin also result ed in better metabolic control than metformin alone for fasting plasma glucose ( -44.8 vs. -20.4 mg/dl ; P = 0.0025 ) , 2-h postpr and ial glucose area under the curve ( -59.0 vs. -18.0 mg/dl ; P = 0.0001 ) , and responder rate ( 70.6 vs. 45.52 % ; P = 0.0014 ) . All therapies were well tolerated . CONCLUSIONS In type 2 diabetic patients , miglitol in combination with metformin gives greater glycemic improvement than metformin monotherapy OBJECTIVE Liraglutide is a long-acting glucagon-like peptide 1 analog design ed for once daily injection . This study assessed the efficacy and safety of liraglutide after 12 weeks of treatment in type 2 diabetic patients . RESEARCH DESIGN AND METHODS A double-blind , r and omized , parallel-group , placebo-controlled trial with an open-label comparator arm was conducted among 193 out patients with type 2 diabetes . The mean age was 56.6 years and the mean HbA(1c ) was 7.6 % across the treatment groups . Patients were r and omly assigned to one of five fixed-dosage groups of liraglutide ( 0.045 , 0.225 , 0.45 , 0.60 , or 0.75 mg ) , placebo , or open-label sulfonylurea ( glimepiride , 1 - 4 mg ) . The primary end point was HbA(1c ) after 12 weeks ; secondary end points were fasting serum glucose , fasting C-peptide , fasting glucagon , fasting insulin , beta-cell function , body weight , adverse events , and hypoglycemic episodes . RESULTS A total of 190 patients were included in the intention-to-treat ( ITT ) analysis . HbA(1c ) decreased in all but the lowest liraglutide dosage group . In the 0.75-mg liraglutide group , HbA(1c ) decreased by 0.75 percentage points ( P < 0.0001 ) and fasting glucose decreased by 1.8 mmol/l ( P = 0.0003 ) compared with placebo . Improvement in glycemic control was evident after 1 week . Body weight decreased by 1.2 kg in the 0.45-mg liraglutide group ( P = 0.0184 ) compared with placebo . The proinsulin-to-insulin ratio decreased in the 0.75-mg liraglutide group ( -0.18 ; P = 0.0244 ) compared with placebo . Patients treated with glimepiride had decreased HbA(1c ) and fasting glucose , but slightly increased body weight . No safety issues were raised for liraglutide ; observed adverse events were mild and transient . CONCLUSIONS A once-daily dose of liraglutide provides efficacious glycemic control and is not associated with weight gain . Adverse events with the drug are mild and transient , and the risk of hypoglycemia is negligible Introduction Severe hypoglycemic events ( SHEs ) are associated with significant morbidity , mortality and costs . However , the more common non-severe hypoglycemic events ( NSHEs ) are less well explored . We investigated the association between reported frequency of NSHEs and SHEs among patients with type 1 diabetes mellitus ( T1DM ) and type 2 diabetes mellitus ( T2DM ) in the PREDICTIVE study . Methods PREDICTIVE was a global , prospect i ve , observational study . Patients with T1DM ( n = 7,420 ) or T2DM ( n = 12,981 ) , starting treatment with insulin detemir , reported the number of NSHEs and SHEs experienced during the 4 weeks prior to baseline and follow-up visits ( mean 14.4 weeks ) . Logistic regression was used to determine the odds ratio ( OR ) of experiencing ≥1 SHE , in patients having 1–4 or ≥5 NSHEs , versus those having 0 NSHEs , while controlling for baseline covariates . Results Hypoglycemia rates were lower at follow-up than baseline . At baseline 59.2 % ( T1DM ) and 18.8 % ( T2DM ) reported any hypoglycemia and at follow-up 39.5 % ( T1DM ) and 8.6 % ( T2DM ) . There was a significant ( P < 0.0001 ) increase in the odds of ≥1 SHEs with increasing frequency of NSHEs in T1DM and T2DM , for both crude and adjusted estimates . At baseline , in T1DM , ORs for ≥1 SHE were 1.92 and 2.13 for 1–4 and ≥5 NSHEs , respectively ; the corresponding ORs in T2DM were 10.83 and 15.36 , respectively . At follow-up , the ORs for ≥1 SHE were 2.01 and 3.20 ( T1DM ) and 18.99 and 24.29 ( T2DM ) for 1–4 and ≥5 NSHEs , respectively . Conclusion A statistically significant association between NSHE and SHE frequency was found in T1DM and T2DM . These data provide a clear rationale for the reduction of hypoglycemic events , regardless of severity , while striving for optimal glycemic control 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 OBJECTIVE To assess the dose-ranging efficacy and safety of LX4211 , a dual inhibitor of sodium – glucose cotransporter ( SGLT ) 1 and SGLT2 , in type 2 diabetes . RESEARCH DESIGN AND METHODS Type 2 diabetic patients inadequately controlled on metformin were r and omly assigned to 75 mg once daily , 200 mg once daily , 200 mg twice daily , or 400 mg once daily of LX4211 or placebo . Primary end point was A1C change from baseline to week 12 . Secondary end points included changes in blood pressure ( BP ) and body weight . RESULTS Baseline characteristics in 299 patients r and omly assigned to LX4211 or placebo in this 12-week dose-ranging study were similar : mean age 55.9 years , A1C 8.1 % ( 65 mmol/mol ) , BMI 33.1 kg/m2 , and BP 124/79 mmHg . LX4211 significantly reduced A1C to week 12 in a dose-dependent manner by 0.42 % ( 4.6 mmol/mol ) , 0.52 % ( 5.7 mmol/mol ) , 0.80 % ( 8.7 mmol/mol ) , and 0.92 % ( 10.0 mmol/mol ) , respectively ( P < 0.001 each ) , compared with 0.09 % ( 1.0 mmol/mol ) for placebo . Greater A1C reductions were produced by 400 mg once a day than 200 mg once a day LX4211 without higher urinary glucose excretion , suggesting a contribution of SGLT1 inhibition . Significant reductions were seen in body weight ( −1.85 kg ; P < 0.001 ) and systolic BP ( −5.7 mmHg ; P < 0.001 ) , but diastolic BP was unchanged ( −1.6 ; P = 0.164 ) . Adverse events with LX4211 were mild to moderate and similar to placebo , including urinary tract infections and gastrointestinal-related events ; genital infections were limited to LX4211 groups ( 0–5.0 % ) . No hypoglycemia occurred . CONCLUSIONS Dual inhibition of SGLT1/SGLT2 with LX4211 produced significant dose-ranging improvements in glucose control without dose-increasing glucosuria and was associated with reductions in weight and systolic BP in metformin-treated patients with type 2 diabetes Aims To examine the efficacy and safety of once‐weekly dulaglutide monotherapy ( 0.75 mg ) compared with placebo and once‐daily liraglutide ( 0.9 mg ) in Japanese patients with type 2 diabetes . Methods This was a phase III , 52‐week ( 26‐week primary endpoint ) , r and omized , double‐blind , placebo‐controlled , open‐label comparator ( liraglutide ) trial comparing 492 Japanese patients with type 2 diabetes ( dulaglutide , n = 281 ; liraglutide , n = 141 ; and placebo , n = 70 ) who were aged ≥20 years . Patients and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide . The primary objective evaluated the superiority of dulaglutide versus placebo on change from baseline in glycated haemoglobin ( HbA1c ) at 26 weeks . Analyses were performed on the full analysis set . Results At 26 weeks , once‐weekly dulaglutide was superior to placebo and non‐inferior to once‐daily liraglutide for HbA1c change from baseline [ least squares mean difference : dulaglutide vs placebo −1.57 % ( 95 % confidence interval −1.79 to −1.35 ) ; dulaglutide vs liraglutide −0.10 % ( 95 % confidence interval −0.27 to 0.07 ) ] . The most frequently reported adverse events were nasopharyngitis , constipation , diarrhoea , nausea , abdominal distension and decreased appetite ; only decreased appetite was different between the dulaglutide and liraglutide groups [ dulaglutide , n = 2 ( 0.7 % ) ; liraglutide , n = 8 ( 5.8 % ) ; p = 0.003 ] . Nine ( 1.8 % ) patients experienced hypoglycaemia [ dulaglutide , n = 6 ( 2.1 % ) ; liraglutide , n = 2 ( 1.5 % ) ; placebo , n = 1 ( 1.4 % ) ] , with no event being severe . Conclusions In Japanese patients with type 2 diabetes , once‐weekly dulaglutide ( 0.75 mg ) was superior to placebo and non‐inferior to once‐daily liraglutide ( 0.9 mg ) for reduction in HbA1c at 26 weeks . Dulaglutide was safe and 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 The aim of this study was to evaluate the dose-dependent effect of dulaglutide , a glucagon-like peptide-1 receptor agonist , on glycaemic control in Japanese patients with type 2 diabetes mellitus who were treated with diet/exercise or oral antidiabetic drug monotherapy . In this r and omised , double-blind , placebo-controlled , parallel-group , 12-week study , patients received once weekly subcutaneous dulaglutide doses of 0.25 , 0.5 , or 0.75 mg ( DU 0.25 , DU 0.5 , and DU 0.75 , respectively ) or placebo ( n=36 , 37 , 35 , and 37 , respectively ) . The primary measure was change from baseline in glycated haemoglobin ( HbA1c ; % ) at 12 weeks . Continuous variables were analysed using a mixed-effects model for repeated measures . Significant dose-dependent reductions in HbA1c were observed ( least squares mean difference versus placebo [ 95 % confidence interval ] ) : DU 0.25=-0.72 % ( -0.95 , -0.48 ) , DU 0.5=-0.97 % ( -1.20 , -0.73 ) , and DU 0.75=-1.17 % ( -1.41 , -0.93 ) ; p<0.001 . Significant improvements in plasma glucose ( PG ) , both fasting and average 7-point self-monitored blood glucose , were also observed with dulaglutide versus placebo ( p<0.001 ) . Dulaglutide was well-tolerated . Gastrointestinal adverse events ( AEs ) were more common in dulaglutide-treated patients , with nausea the most frequent ( 8 [ 5.5 % ] ) . Few dulaglutide-treated patients discontinued due to AEs ( 4 [ 3.7 % ] ) , and no serious AEs related to study medication occurred . Three patients ( DU 0.5=1 and DU 0.75=2 ) reported asymptomatic hypoglycaemia ( PG ≤70 mg/dL ) . The observed dose-dependent reduction in HbA1c and acceptable safety profile support further clinical development of dulaglutide for treatment of type 2 diabetes mellitus in Japan 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 OBJECTIVE This study evaluates the ability of the incretin mimetic exenatide ( exendin-4 ) to improve glycemic control in patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses . RESEARCH DESIGN AND METHODS A triple-blind , placebo-controlled , 30-week study at 82 U.S. sites was performed with 336 r and omized patients . In all , 272 patients completed the study . The intent-to-treat population baseline was 53 + /- 10 years with BMI of 34.2 + /- 5.9 kg/m(2 ) and HbA(1c ) of 8.2 + /- 1.1 % . After 4 weeks of placebo , subjects self-administered 5 microg exenatide or placebo subcutaneously twice daily for 4 weeks followed by 5 or 10 microg exenatide , or placebo subcutaneously twice daily for 26 weeks . All subjects continued metformin therapy . RESULTS At week 30 , HbA(1c ) changes from baseline + /- SE for each group were -0.78 + /- 0.10 % ( 10 microg ) , -0.40 + /- 0.11 % ( 5 microg ) , and + 0.08 + /- 0.10 % ( placebo ; intent to treat ; adjusted P < 0.002 ) . Of evaluable subjects , 46 % ( 10 microg ) , 32 % ( 5 microg ) , and 13 % ( placebo ) achieved HbA(1c ) < or = 7 % ( P < 0.01 vs. placebo ) . Exenatide-treated subjects displayed progressive dose-dependent weight loss ( -2.8 + /- 0.5 kg [ 10 microg ] , -1.6 + /- 0.4 kg [ 5 microg ] ; P < 0.001 vs. placebo ) . The most frequent adverse events were gastrointestinal in nature and generally mild to moderate . Incidence of mild to moderate hypoglycemia was low and similar across treatment arms , with no severe hypoglycemia . CONCLUSIONS Exenatide was generally well tolerated and reduced HbA(1c ) with no weight gain and no increased incidence of hypoglycemia in patients with type 2 diabetes failing to achieve glycemic control with metformin 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 Background In recent years , several oral antidiabetic drugs with new mechanisms of action have become available , exp and ing the number of treatment options . Sodium/glucose cotransporter-2 ( SGLT2 ) inhibitors are a new class of oral antidiabetic drugs with an insulin-independent mechanism promoting urinary glucose excretion . We report the results of a combined Phase 2 and 3 clinical study ( Japic CTI-101349 ) of the SGLT2 inhibitor tofogliflozin ( CSG452 , RG7201 ) in Japanese patients with type 2 diabetes mellitus . Methods The efficacy and safety of tofogliflozin were assessed in this multicenter , placebo-controlled , r and omized , double-blind parallel-group study involving 230 patients with type 2 diabetes mellitus with inadequate glycemic control on diet/exercise therapy . Between 30 October 2010 and 28 February 2012 , patients at 33 centers were r and omized to either placebo ( n = 56 ) or tofogliflozin ( 10 , 20 , or 40 mg ; n = 58 each ) orally , once daily for 24 weeks . The primary efficacy endpoint was the change from baseline in HbA1c at week 24 . Results Overall , 229 patients were included in the full analysis set ( placebo : n = 56 ; tofogliflozin 10 mg : n = 57 ; tofogliflozin 20 and 40 mg : n = 58 each ) . The least squares ( LS ) mean change ( 95 % confidence interval ) from baseline in HbA1c at week 24 was −0.028 % ( −0.192 to 0.137 ) in the placebo group , compared with −0.797 % ( −0.960 to −0.634 ) in the tofogliflozin 10 mg group , −1.017 % ( −1.178 to −0.856 ) in the tofogliflozin 20 mg group , and −0.870 % ( −1.031 to −0.709 ) in the tofogliflozin 40 mg group ( p < 0.0001 for the LS mean differences in all tofogliflozin groups vs placebo ) . There were also prominent decreases in fasting blood glucose , 2-h postpr and ial glucose , and body weight in all tofogliflozin groups compared with the placebo group . The main adverse events were hyperketonemia , ketonuria , and pollakiuria . The incidence of hypoglycemia was low . Furthermore , most adverse events were classified as mild or moderate in severity . Conclusions Tofogliflozin 10 , 20 , or 40 mg administered once daily as monotherapy significantly decreased HbA1c and body weight , and was generally well tolerated in Japanese patients with type 2 diabetes mellitus . Phase 3 studies were recently completed and support the findings of this combined Phase 2 and 3 study .Trial registration This study was registered in the JAPIC clinical trials registry ( ID : Japic%CTI-101349 ) Aims To evaluate the dose – response relationship of lixisenatide ( AVE0010 ) , a glucagon-like peptide-1 ( GLP-1 ) receptor agonist , in metformin-treated patients with Type 2 diabetes . Methods R and omized , double-blind , placebo-controlled , parallel-group , 13 week study of 542 patients with Type 2 diabetes inadequately controlled [ glycated haemoglobin ( HbA1c ) ≥ 7.0 and < 9.0 % ( ≥ 53 and < 75 mmol/mol ) ] on metformin ( ≥ 1000 mg/day ) treated with subcutaneous lixisenatide doses of 5 , 10 , 20 or 30 μg once daily or twice daily or placebo . The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population . Results Lixisenatide significantly improved mean HbA1c from a baseline of 7.55 % ( 59.0 mmol/mol ) ; respective mean reductions for 5 , 10 , 20 and 30 μg doses were 0.47 , 0.50 , 0.69 and 0.76 % ( 5.1 , 5.5 , 7.5 and 8.3 mmol/mol ) , on once-daily and 0.65 , 0.78 , 0.75 and 0.87 % ( 7.1 , 8.5 , 8.2 and 9.5 mmol/mol ) on twice-daily administrations vs. 0.18 % ( 2.0 mmol/mol ) with placebo ( all P < 0.01 vs. placebo ) . Target HbA1c < 7.0 % ( 53 mmol/mol ) at study end was achieved in 68 % of patients receiving 20 and 30 μg once-daily lixisenatide vs. 32 % receiving placebo ( P < 0.0001 ) . Dose-dependent improvements were observed for fasting , postpr and ial and average self-monitored seven-point blood glucose levels . Weight changes ranged from −2.0 to −3.9 kg with lixisenatide vs. −1.9 kg with placebo . The most frequent adverse event was mild-to-moderate nausea . Conclusions Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin . Dose – response relationships were seen for once- and twice-daily regimens , with similar efficacy levels , with a 20 μg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio . This new , once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies OBJECTIVE Appropriate glycemic control is fundamental to diabetes care , but aggressive glucose targets and intensive therapy may unintentionally increase episodes of hypoglycemia . We quantified the burden of severe hypoglycemia requiring medical intervention in a well-defined population of insured individuals with diabetes receiving care in integrated health care delivery systems across the U.S. RESEARCH DESIGN AND METHODS This observational cohort study included 917,440 adults with diabetes receiving care during 2005 to 2011 at participating SUrveillance , PREvention , and ManagEment of Diabetes Mellitus ( SUPREME-DM ) network sites . Severe hypoglycemia rates were based on any occurrence of hypoglycemia-related ICD-9 codes from emergency department or inpatient medical encounters and reported overall and by age , sex , comorbidity status , antecedent A1C level , and medication use . RESULTS Annual rates of severe hypoglycemia ranged from 1.4 to 1.6 events per 100 person-years . Rates of severe hypoglycemia were higher among those with older age , chronic kidney disease , congestive heart failure , cardiovascular disease , depression , and higher A1C levels , and in users of insulin , insulin secretagogues , or β-blockers ( P < 0.001 for all ) . Changes in severe hypoglycemia occurrence over time were not clinical ly significant in the cohort as a whole but were observed in subgroups of individuals with chronic kidney disease , congestive heart failure , and cardiovascular disease . CONCLUSIONS Risk of severe hypoglycemia in clinical setting s is considerably higher in identifiable patient subgroups than in r and omized controlled trials . Strategies that reduce the risk of hypoglycemia in high-risk patients are needed 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 OBJECTIVE To investigate the dose-response relationship of semaglutide versus placebo and open-label liraglutide in terms of glycemic control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS This was a 12-week , r and omized , double-blind phase 2 trial . Patients ( n = 415 ) were r and omized to receive a subcutaneous injection of semaglutide once weekly without dose escalation ( 0.1–0.8 mg ) or with dose escalation ( E ) ( 0.4 mg steps to 0.8 or 1.6 mg E over 1–2 weeks ) , open-label liraglutide once daily ( 1.2 or 1.8 mg ) , or placebo . The primary end point was change in HbA1c level from baseline . Secondary end points included change in body weight , safety , and tolerability . RESULTS Semaglutide dose-dependently reduced the level of HbA1c from baseline ( 8.1 ± 0.8 % ) to week 12 by up to −1.7 % , and body weight by up to −4.8 kg ( 1.6 mg E , P < 0.001 vs. placebo ) . Up to 81 % of patients achieved an HbA1c level of < 7 % . HbA1c level and weight reductions with semaglutide 1.6 mg E were greater than those with liraglutide 1.2 and 1.8 mg ( based on unadjusted CIs ) , but adverse events ( AEs ) and withdrawals occurred more frequently . The incidence of nausea , vomiting , and withdrawal due to gastrointestinal AEs increased with the semaglutide dose ; most events were mild to moderate , transient , and ameliorated by dose escalation . There were no major episodes of hypoglycemia and few cases of injection site reactions . CONCLUSIONS After 12 weeks , semaglutide dose-dependently reduced HbA1c level and weight in patients with type 2 diabetes . No unexpected safety or tolerability concerns were identified ; gastrointestinal AEs typical of glucagon-like peptide 1 receptor agonists were mitigated by dose escalation . On this basis , weekly semaglutide doses of 0.5 and 1.0 mg with a 4-week dose escalation were selected for phase 3 The aim of the study was to evaluate the efficacy and safety of vildagliptin added to metformin in patients with type 2 diabetes mellitus . A multicentre , double-blind , r and omized , placebo-controlled , 24-week study in patients inadequately controlled with metformin ( HbA(1c ) 7.5 - 11 % ) was design ed . Patients were r and omized to vildagliptin ( Galvus ) 100 mg given in the morning ( AM ) , vildagliptin 100 mg given in the evening ( PM ) , or placebo . The primary objective was to demonstrate that HbA(1c ) reduction with once-daily vildagliptin 100 mg AM dosing is superior to placebo . Change from baseline to study endpoint in adjusted mean ( SE ) HbA(1c ) improved significantly with vildagliptin AM dosing ( -0.66 [ 0.11 ] versus 0.17 % [ 0.11 ] with placebo ; p < 0.001 ) . Subgroup analyses revealed that HbA(1c ) reduction from baseline was greatest in those patients who had the highest baseline HbA(1c ) levels . According to a predefined set of response criteria , the percentage of responder patients was significantly greater in the vildagliptin AM dosing group than in the placebo group for all responder definitions . Further analysis also revealed comparable efficacy between AM and PM dosing . Body weight remained generally stable in the combined vildagliptin group ( + 0.06 kg ) and decreased with placebo ( -0.69 kg ) ; the incidence of adverse events was similar with vildagliptin AM dosing and placebo ( 30.4 and 34.4 % , respectively ) . Vildagliptin 100 mg given as a morning dose is an effective and well-tolerated treatment option in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy , and is equally efficacious when given as either a morning or evening dose OBJECTIVE The objective of this study is to describe current self-monitoring of blood glucose ( SMBG ) practice for patients with type 2 diabetes by treatment type and adherence with healthcare professional advice concerning SMBG . In addition , the study aims to investigate the association of SMBG and self-reported episodes of low blood glucose . DESIGN AND SETTING This cross-sectional survey design study was carried out on patients with type 2 diabetes aged 18 years or over , attending community pharmacies in 97 sites across the United Kingdom . METHODS Patients picking up a prescription for blood glucose test strips or diabetes medicine from a community pharmacist were asked to complete a question naire . The pharmacist was available to assist if requested . Questions included : self-reports of frequency of blood glucose testing ; type of diabetes treatment ; advice given by healthcare professionals about frequency of blood glucose testing ; frequency of episodes of low blood glucose ; and last known HbA(1c ) level . The final sample size was 554 respondents , who were grouped for analysis as follows : those being treated with insulin , either alone or with any oral medication ( n = 167 ) ; those being treated with sulfonylureas , either alone or with any oral medication ( n = 187 ) ; and those being treated with any other medication , or controlled by diet and exercise alone ( n = 202 ) . RESULTS Frequency of SMBG was higher in patients using insulin ( median 10 times per week , Q ( 1 ) , Q ( 3 ) = 4.5 , 14 ) than in patients on treatments other than insulin ( four times per week , Q ( 1 ) , Q ( 3 ) = 2 , 7 , p < 0.001 ) . SMBG was carried out at the same frequency in patients not treated with insulin regardless of whether they were prescribed sulfonylureas . Greater frequency of SMBG was associated with self-reports of one or more episodes of low blood glucose in the previous six months . CONCLUSIONS Among patients with type 2 diabetes , those treated with insulin used SMBG at a greater frequency than those not treated with insulin . Increased frequency of testing was associated with increased frequency of self-reported episodes of low blood glucose , even among patients not taking insulin or sulfonylureas . This raises the possibility that episodes of hypoglycaemia may not be accurately identified , leading to unnecessary fear , or conversely that treatment is not being adjusted to avoid such morbidity . Although further work is needed to explore this association in a representative , prospect i ve cohort of patients , possible explanations for reports of low-blood glucose should be discussed with patients using SMBG more frequently to ensure they are able to accurately identify episodes of hypoglycaemia 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 Aims This double‐blind , r and omized , placebo‐controlled trial ( http:// clinical trials.gov NCT02453555 ) evaluated the efficacy and safety of empagliflozin ( Empa ) 10 or 25 mg as add‐on to linagliptin ( Lina ) 5 mg ( fixed‐dose combination , Empa/Lina 10/5 or 25/5 ) in insufficiently controlled Japanese type 2 diabetes patients . Methods The trial ( 40 sites ; May 2015‐March 2017 ) involved screening 433 adults ( ≥20 years ) who were treatment‐naive or were using one oral antidiabetic drug for ≥12 weeks , which was discontinued at enrolment . Patients with HbA1c 7.5%‐10.0 % after ≥16 weeks of using Lina ( pre‐enrolment or during a 16‐week , open‐label period ) and 2 weeks of using placebo ( Plc ) for Empa/Lina 10/5 , plus Lina , were r and omized ( 2:1 ) to once‐daily Empa/Lina 10/5 ( n = 182 ) or Plc/Lina 10/5 ( n = 93 ) for 24 weeks . Patients with HbA1c ≥ 7.0 % at Week 24 received Empa/Lina up‐titrated to 25/5 ( n = 126 ) or the corresponding placebo ( n = 80 ) , per r and omization , from Week 28 ; 172 Empa/Lina and 84 Plc/Lina patients completed 52 weeks . Results Change from baseline in HbA1c was greater ( P < .0001 ) with Empa/Lina than with Plc/Lina at Week 24 ( primary outcome , −0.93 % vs 0.21 % ; adjusted mean difference , −1.14 % ) and Week 52 ( −1.16 % vs 0.06 % ; adjusted mean difference , −1.22 % ) . More patients with HbA1c < 7.0 % and greater decreases in fasting plasma glucose , body weight and systolic blood pressure were seen in the Empa/Lina group than in the Plc/Lina group . Empa/Lina was well tolerated . The adverse events that were more frequent with Empa/Lina were known empagliflozin‐associated events ( eg , increased urination , increased blood ketones ) . There were no adjudication‐confirmed diabetic ketoacidosis events or lower limb amputations . Conclusions These results support the notion that empagliflozin‐linagliptin in fixed‐dose combination is a therapeutic option for Japanese patients 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 The purpose of this phase 2 , multicentre , r and omized , double-blind , placebo-controlled , 12-week dose-ranging study was to assess the efficacy , safety , and tolerability of the dipeptidyl peptidase-IV ( DPP-IV ) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose of metformin . Men and women with inadequate glycaemic control with metformin as their sole diabetes medication were r and omized to placebo or PF-734200 2 mg , 5 mg , 10 mg , or 20 mg every day . A population subset underwent mixed meal tolerance tests ( MMTT ) at baseline and week 12 . A total of 301 subjects were treated . At week 12 , PF-734200 doses of ≥5 mg produced a statistically significant reduction in haemoglobin A ( 1C ) ( HbA ( 1c ) ) compared with placebo . The mean ( 95 % confidence interval ) placebo-adjusted changes in HbA ( 1c ) were -0.31 % ( -0.70 to 0.08 ) , -0.74 % ( -1.12 to -0.36 ) , -0.70 % ( -1.02 to -0.38 ) , and -0.75 % ( -1.07 to -0.43 ) for the 2 mg , 5 mg , 10 mg , and 20 mg doses , respectively . PF-734200 20 mg significantly reduced glucose area under the curve following MMTT ( -12.8 % [ -22.9 to -2.7 ] ; p=0.003 ) compared with placebo . The reductions observed with other doses were not statistically significant . PF-734200 was safe and well tolerated at all doses tested when added to metformin . PF-734200 safely and effectively lowered HbA ( 1c ) in subjects receiving metformin . The 20 mg dose provided the greatest improvements in post-pr and ial glucose 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 To evaluate the efficacy and safety of twice‐daily dosing of dapagliflozin and metformin , exploring the feasibility of a fixed‐dose combination Summary Glucagon-like peptide 1 ( GLP-1 ) ( 7 - 36 amide ) is a physiological incretin hormone that is released after nutrient intake from the lower gut and stimulates insulin secretion at elevated plasma glucose concentrations . Previous work has shown that even in Type 2 ( non-insulin-dependent ) diabetic patients GLP-1 ( 7 - 36 amide ) retains much of its insulinotropic action . However , it is not known whether the magnitude of this response is sufficient to normalize plasma glucose in Type 2 diabetic patients with poor metabolic control . Therefore , in 10 Type 2 diabetic patients with unsatisfactory metabolic control ( HbAlc 11.6±1.7 % ) on diet and sulphonylurea therapy ( in some patients supplemented by metformin or acarbose ) , 1.2 pmol ×kg−1 × min−1 GLP-1 ( 7 - 36 amide ) or placebo was infused intravenously in the fasting state ( plasma glucose 13.1±0.6 mmol/l ) . In all patients , insulin ( by 17.4±4.7 nmol ×1−1 × min ; p=0.0157 ) and C-peptide ( by 228.0±39.1 nmol × 1−1 × min ; p=0.0019 ) increased significantly over basal levels , glucagon was reduced ( by -1418±308 pmol ×1−1 × min ) and plasma glucose reached normal fasting concentrations ( 4.9±0.3 mmol/l ) within 4 h of GLP-1 ( 7 - 36 amide ) administration , but not with placebo . When normal fasting plasma glucose concentrations were reached insulin returned towards basal levels and plasma glucose concentrations remained stable despite the ongoing infusion of GLP-1 ( 7 - 36 amide ) . Therefore , exogenous GLP-1 ( 7 - 36 amide ) is an effective means of normalizing fasting plasma glucose concentrations in poorly-controlled Type 2 diabetic patients . The glucose-dependence of insulinotropic actions of GLP-1 ( 7 - 36 amide ) appears to be retained in such patients AIMS To evaluate dose-response efficacy and safety of once-daily human GLP-1 analog liraglutide in Japanese subjects with type 2 diabetes . METHODS Patients ( 226 , treated with diet with/without OADs , mean HbA(1c ) 8.30 % , mean BMI 23.9kg/m(2 ) ) were r and omized after OAD discontinuation and washout to receive liraglutide 0.1 , 0.3 , 0.6 or 0.9 mg once daily , or placebo in double-blind , parallel-group design for 14 weeks . RESULTS Liraglutide dose levels reduced HbA(1c ) versus placebo ( by 0.79 % , 1.22 % , 1.64 % and 1.85 % , respectively ; p<0.0001 for linear contrast ) . Liraglutide 0.9mg/day result ed in 75 % of patients achieving HbA(1c ) < 7.0 % and 57 % achieving HbA(1c ) < 6.5 % . There were no major or minor hypoglycemic events . Liraglutide also reduced , with significant dose-response ( each p<0.0001 for linear contrast ) versus placebo : fasting plasma glucose ( up to 2.5mmol/L ) , postpr and ial ( 0 - 3h ) glucose excursion ( up to 12.8mmol/(Lh ) ) ; and increased postpr and ial insulin secretion ( up to 23.0microU/(mLh ) ) and beta-cell function as evaluated by HOMA-beta ( up to around 20.0(microU/mL)/(mg/dL ) ) . Body weight was unchanged ; no development of liraglutide antibodies was detected . CONCLUSIONS Liraglutide was highly effective and well tolerated at doses up to 0.9mg/day in Japanese patients with type 2 diabetes , allowing glycemic control without weight gain or hypoglycemia BACKGROUND This study evaluated the effect of vildagliptin + metformin on glycemic control and β-cell function in type 2 diabetes patients . SUBJECTS AND METHODS One hundred seventy-one type 2 diabetes patients , naive to antidiabetes therapy and with poor glycemic control , were instructed to take metformin for 8±2 months up to a mean dosage of 2,500±500 mg/day ; then they were r and omly assigned to add vildaglipin 50 mg twice a day or placebo for 12 months . We evaluated at 3 , 6 , 9 , and 12 months : body mass index , glycemic control , fasting plasma insulin , homeostasis model assessment insulin resistance index ( HOMA-IR ) , homeostasis model assessment β-cell function index ( HOMA-β ) , fasting plasma proinsulin , proinsulin/fasting plasma insulin ratio , C-peptide , glucagon , adiponectin , and high-sensitivity C-reactive protein . Before and at 12 months after the addition of vildagliptin , patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp , with subsequent arginine stimulation , to assess insulin sensitivity and insulin secretion . RESULTS After 12 months of treatment , vildagliptin + metformin gave a better decrease of body weight , glycemic control , HOMA-IR , and glucagon and a better increase of HOMA-β compared with placebo + metformin . Regarding the measures of β-cell function , treatment-induced changes in M-value , first- and second-phase C-peptide response to glucose , and C-peptide response to arginine were significantly higher in the vildagliptin + metformin group compared with the placebo + metformin group . CONCLUSION The addition of vildagliptin to metformin gave a better improvement of glycemic control , insulin resistance , and β-cell function compared with metformin alone 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 OBJECTIVE Dapagliflozin is a highly selective , orally active inhibitor of renal sodium-glucose cotransporter 2 that reduces hyperglycemia by increasing urinary glucose excretion . The goal of this study was to evaluate dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes whose disease was inadequately controlled with diet and exercise . METHODS In this Phase III , multicenter , parallel-group , double-blind study , drug-naive patients with glycosylated hemoglobin ( HbA1c ) levels ≥7.0 % to ≤10.5 % ( ≥53-≤91 mmol/mol ) were r and omized ( by using an interactive voice response system ) to receive placebo ( n = 132 ) , dapagliflozin 5 mg ( n = 128 ) , or dapagliflozin 10 mg ( n = 133 ) . The primary end point was mean change from baseline in HbA1c level at week 24 ( last-observation-carried-forward ) . Secondary end points included changes in fasting plasma glucose , 2-hour postpr and ial glucose , body weight , and other glycemic parameters . RESULTS Baseline characteristics were balanced across groups . Most patients ( 89 % ) were Chinese , median disease duration was 0.2 year , and mean HbA1c level was 8.26 % . Most patients ( 87 % ) completed the study . At week 24 , mean reductions in HbA1c were -0.29 % for placebo versus -1.04 % and -1.11 % for dapagliflozin 5 and 10 mg , respectively ( P < 0.0001 for both doses ) . Changes in fasting plasma glucose were 2.5 , -25.1 , and -31.6 mg/dL ( 0.14 , -1.39 , and -1.75 mmol/L ) for placebo , dapagliflozin 5 mg , and dapagliflozin 10 mg . Changes in 2-hour postpr and ial glucose were 1.1 , -46.8 , and -54.9 mg/dL ( 0.06 , -2.60 , and -3.05 mmol/L ) . Reductions in body weight were -0.27 , -1.64 , and -2.25 kg . Proportions of patients achieving HbA1c levels < 7.0 % ( 53 mmol/mol ) were 21.3 % , 42.6 % , and 49.8 % . Adverse events ( AEs ) occurred in 63.6 % , 61.7 % , and 60.9 % of patients , and serious AEs occurred in 1.5 % , 3.9 % , and 3.0 % of patients . No deaths occurred . Hypoglycemia was uncommon ( 1.5 % , 0.8 % , and 0.8 % ) ; no hypoglycemic event led to discontinuation . Genital infections occurred in 0.8 % , 3.1 % , and 4.5 % of patients and urinary tract infections in 3.0 % , 3.9 % , and 5.3 % of patients . No AEs of renal infection or pyelonephritis were reported . No changes in renal function or AEs of renal failure occurred . CONCLUSIONS Compared with placebo , dapagliflozin 5 and 10 mg demonstrated clinical ly and statistically significant improvements in HbA1c levels after 24 weeks of treatment . Dose-dependent , statistically significant reductions in fasting plasma glucose , postpr and ial glucose , and weight were also observed for both doses compared with placebo . AEs and serious AEs were balanced across groups , with low rates of hypoglycemia and no increase in renal events . Genital infections and urinary tract infections were more common with dapagliflozin . Dapagliflozin as monotherapy in these drug-naive Asian patients was well tolerated , significantly improving glycemic control with the additional benefit of weight loss OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE 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 evaluate the efficacy , safety , and tolerability of multiple doses of ipragliflozin . This novel selective inhibitor of sodium glucose co-transporter 2 is in clinical development for the treatment of patients with type 2 diabetes mellitus ( T2DM ) . METHODS In a 12-week , multicenter , double-blind , r and omized , active- and placebo-controlled dose-finding study , patients were r and omized to one of four ipragliflozin treatment groups ( 12.5 , 50 , 150 , and 300 mg once daily ) , placebo , or active control ( metformin ) . The primary efficacy outcome was the mean change from baseline to Week 12 of glycosylated hemoglobin ( HbA1c ) compared with placebo . RESULTS Ipragliflozin showed a dose-dependent decrease in HbA1c of -0.49 % to -0.81 % at Week 12 compared with placebo ( P<0.001 ) ; a decrease of -0.72 % was seen with metformin . Among the ipragliflozin groups there was also a dose-dependent reduction in body weight of up to 1.7 kg . Proportions of patients experiencing treatment-emergent adverse events were similar across all groups : ipragliflozin ( 45.7 - 58.8 % ) , placebo ( 62.3 % ) , and metformin ( 59.4 % ) . No clinical ly relevant effects were observed for other safety measures . CONCLUSIONS After 12 weeks of treatment , ipragliflozin dose-dependently decreased HbA1c , with ipragliflozin ≥50 mg/day in patients with T2DM ; an effect comparable to metformin . No safety or tolerability concerns were identified AIMS Many patients with type 2 diabetes are suboptimally managed with currently available therapies . Dapagliflozin , a sodium-glucose co-transporter-2 inhibitor , has shown efficacy in reducing diabetic hyperglycaemia . This study assessed efficacy of three lower doses in recently diagnosed patients . METHODS This phase 3 , r and omized , double-blind , placebo-controlled study assigned treatment-naïve patients to placebo or dapagliflozin monotherapy ( 1 , 2.5 or 5 mg ) daily for 24 weeks . Patients were antidiabetic drug-naïve with inadequate glycaemic control [ haemoglobin A1c ( HbA1c ) ≥7.0 and ≤10.0 % ] . The primary efficacy endpoint was change in HbA1c from baseline . Secondary endpoints included changes in body weight and fasting plasma glucose ( FPG ) , and proportions achieving HbA1c < 7 % . RESULTS A total of 282 patients with type 2 diabetes were r and omly assigned to one of four treatment groups . Baseline characteristics were similar across groups . At week 24 , mean HbA1c reduction was significantly greater with dapagliflozin : -0.68 % for 1 mg , -0.72 % for 2.5 mg , -0.82 % for 5 mg , versus 0.02 % for placebo ( p < 0.0001 ) ; compared to mean baseline values of 7.8 - 8.1 % . Mean FPG reduction was significantly greater for all dapagliflozin groups versus placebo ( p < 0.02 ) , as was mean weight reduction ( p < 0.003 ) . During the treatment period , 19.1 % of placebo-treated patients received rescue medication or discontinued because of poor glycaemic control versus 6.9 , 4.1 and 5.9 % for dapagliflozin 1 , 2.5 and 5 mg , respectively . Percentages of patients experiencing ≥1 adverse event were similar across groups . CONCLUSION Dapagliflozin at doses of 1 , 2.5 and 5 mg/day is effective in reducing glycaemic levels and body weight in treatment-naïve patients with type 2 diabetes . Dapagliflozin was generally well tolerated . This insulin-independent mechanism suggests a new treatment for type 2 diabetes AIM To investigate the efficacy and safety of ertugliflozin , in a phase II dose-ranging study , in patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled on metformin . METHODS A total of 328 patients [ mean T2DM duration , 6.3 years ; mean glycated haemoglobin ( HbA1c ) , 8.1 % ] were r and omized to once-daily ertugliflozin ( 1 , 5 , 10 , 25 mg ) , sitagliptin ( 100 mg ) or placebo , for 12 weeks . The primary efficacy endpoint was change from baseline to week 12 in HbA1c concentration and the secondary efficacy endpoints were changes from baseline to week 12 in body weight , fasting plasma glucose ( FPG ) and systolic/diastolic blood pressure ( SBP/DBP ) . Safety and tolerability were also monitored . RESULTS Ertugliflozin ( 1 - 25 mg/day ) produced significant reductions in HbA1c concentration [ placebo-corrected least-squares mean ( LSM ) -0.45 % ( 1 mg ) to -0.72 % ( 25 mg ) ; p ≤ 0.002 , similar to sitagliptin ( -0.76 % ; p = 0.0001 ) ] , FPG ( LSM -1.17 to -1.90 mmol/l ; p < 0.0001 ) and body weight ( -1.15 to -2.15 % ; p < 0.0001 ) . The LSM SBP decreased by -3.4 to -4.0 mmHg from baseline with ertugliflozin 5 - 25 mg/day . No reductions in body weight or blood pressure were observed with sitagliptin . After r and omization , 2.7 % of patients ( 9/328 ) withdrew because of adverse events ( AEs ) ; the frequency of AEs was evenly distributed across groups . No dose-related increase in AE frequency occurred with ertugliflozin . Hypoglycaemia was reported in 5 ( 1.5 % ) r and omized participants ( all in the ertugliflozin group ) . The frequency of urinary tract infection was 3.2 % for ertugliflozin ( pooled across groups ) , 1.8 % for sitagliptin , 7.4 % for placebo , and the frequency of genital fungal infections was 3.7 % for ertugliflozin ( pooled ) versus 1.9 % for placebo . CONCLUSION Ertugliflozin ( 1 - 25 mg/day ) improved glycaemic control , body weight and blood pressure in patients with T2DM suboptimally controlled on metformin , and was well tolerated 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 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 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 BACKGROUND Trelagliptin is a novel once-weekly oral DPP-4 inhibitor . We assessed the efficacy and safety of trelagliptin versus the daily oral DPP-4 inhibitor alogliptin in Japanese patients with type 2 diabetes . METHODS We did a r and omised , double-blind , active-controlled , parallel-group , phase 3 , non-inferiority study at 26 sites in Japan . We included individuals with type 2 diabetes inadequately controlled by diet and exercise . We r and omly assigned patients ( 2:2:1 ) to receive trelagliptin ( 100 mg ) once per week , alogliptin ( 25 mg ) once per day , or placebo for 24 weeks . R and omisation was done electronically and independently from the study with permuted blocks of ten patients . Patients and clinicians were masked to group assignment . Patients in the trelagliptin group were given trelagliptin once a week and oral alogliptin placebo every day , whereas patients in the alogliptin group were given oral trelagliptin placebo once a week and oral alogliptin every day ( double-dummy design ) . Patients in the placebo group were given an oral alogliptin placebo once a day and an oral trelagliptin placebo once a week . Our primary outcome was between-groups difference in change in HbA1c concentration from baseline to the end of treatment . The non-inferiority margin was 0·4 % . Our analysis included all patients who were r and omised and received at least one dose of study drug . The study is registered with Clinical Trials.gov , number NCT01632007 . FINDINGS Between May 26 , 2012 , and Nov 20 , 2012 , we enrolled 357 patients . 243 patients were included in the analysis ( 101 for trelagliptin , 92 for alogliptin , and 50 for placebo ) . In the primary analysis , the least squares mean change in HbA1c concentration was -0·33 % in the trelagliptin group ( SE 0·059 ) and -0·45 % in the alogliptin group ( 0·061 ) based on the ANCOVA model . The least squares mean difference ( trelagliptin minus alogliptin ) of change from baseline in HbA1c concentration was 0·11 % ( 95 % CI -0·054 to 0·281 ) . Trelagliptin was non-inferior to alogliptin . Both active groups had significantly reduced mean HbA1c concentrations at end of treatment compared with placebo ( p<0·0001 ) . The frequency of adverse events was similar between groups . No hypoglycaemia was reported with trelagliptin and the drug was well tolerated . INTERPRETATION The once-weekly DPP-4 inhibitor trelagliptin showed similar efficacy and safety to alogliptin once daily in Japanese patients with type 2 diabetes . Trelagliptin could be a useful new antidiabetes drug that needs to be given once a week . FUNDING Takeda Pharmaceutical Company AIM This Phase IIb , r and omized , double-blind , placebo-controlled trial evaluated the efficacy , safety , tolerability and pharmacokinetics of empagliflozin in patients with type 2 diabetes . METHODS Four hundred and eight patients ( treatment-naïve or after a 4-week wash-out period ) were r and omized to receive empagliflozin 5 , 10 or 25 mg once daily , placebo or open-label metformin for 12 weeks . The primary endpoint was change in haemoglobin A1c ( HbA1c ) after 12 weeks . RESULTS After 12 weeks ' treatment , empagliflozin showed dose-dependent reductions in HbA1c from baseline [ 5 mg : -0.4 % , 10 mg : -0.5 % , 25 mg : -0.6 % ; all doses p < 0.0001 vs. placebo ( + 0.09 % ) ] . Fasting plasma glucose ( FPG ) decreased with empagliflozin [ 5 mg : -1.29 mmol/l , 10 mg : -1.61 mmol/l , 25 mg : -1.72 mmol/l ; all doses p < 0.0001 vs. placebo ( + 0.04 mmol/l ) ] . Body weight decreased in all empagliflozin groups ( all doses p < 0.001 vs. placebo ) . The incidence of adverse events ( AEs ) was similar in the placebo ( 32.9 % ) and empagliflozin ( 29.1 % ) groups . The most frequently reported AEs on empagliflozin were pollakiuria ( 3.3 % vs. 0 % for placebo ) , thirst ( 3.3 % vs. 0 % for placebo ) and nasopharyngitis ( 2.0 % vs. 1.2 % for placebo ) . AEs consistent with urinary tract infections ( UTIs ) were reported in four ( 1.6 % ) patients on empagliflozin vs. one ( 1.2 % ) on placebo . Genital infections were reported in five ( 2 % ) patients on empagliflozin vs. 0 % on placebo . No UTIs or genital infections led to premature discontinuation . CONCLUSIONS In patients with type 2 diabetes , empagliflozin result ed in dose-dependent , clinical ly meaningful reductions in HbA1c and FPG , and reductions in body weight compared with placebo . Empagliflozin was well-tolerated with a favourable safety profile OBJECTIVE To assess the efficacy and safety of dapagliflozin as add-on therapy in patients with type 2 diabetes who were inadequately controlled with a dipeptidyl peptidase-4 inhibitor with or without metformin . RESEARCH DESIGN AND METHODS In this 24-week , multicenter , r and omized , double-blind , placebo-controlled , parallel-group , phase 3 study with a 24-week blinded extension period , 432 patients were r and omized to receive dapagliflozin 10 mg/day or placebo added to sitagliptin ( 100 mg/day ) ± metformin ( ≥1,500 mg/day ) . RESULTS Baseline HbA1c and FPG levels were 7.9 % ( 63.0 mmol/mol ) and 162.2 mg/dL ( 9.0 mmol/L ) for the dapagliflozin group and 8.0 % ( 64.0 mmol/mol ) and 163 mg/dL ( 9.0 mmol/L ) for placebo . At week 24 , dapagliflozin significantly reduced mean HbA1c levels ( –0.5 % [ –4.9 mmol/mol ] ) versus placebo ( 0.0 % [ + 0.4 mmol/mol ] ) . Dapagliflozin reduced body weight versus placebo ( –2.1 and –0.3 kg ) and reduced HbA1c levels in patients with baseline values ≥8.0 % ( –0.8 % [ 8.7 mmol/mol ] and 0.0 % [ 0.3 mmol/mol ] ) and fasting plasma glucose levels ( –24.1 mg/dL [ –1.3 mmol/L ] and 3.8 mg/dL [ 0.2 mmol/L ] ) . Similar results were observed when data were stratified by background therapy . Glycemic and weight benefits observed at week 24 were maintained through week 48 . Changes from baseline in systolic blood pressure at week 8 were not significantly different between treatment groups . Over 48 weeks , fewer patients receiving dapagliflozin were discontinued or rescued for failing to achieve glycemic targets compared with placebo . Adverse events were balanced between groups , and discontinuation rates were low . At week 48 , signs and symptoms suggestive of genital infection were more frequent with dapagliflozin ( 9.8 % ) than with placebo ( 0.4 % ) . Signs and symptoms suggestive of urinary tract infection were balanced between dapagliflozin ( 6.7 % ) and placebo ( 6.2 % ) . CONCLUSIONS These results suggest that in patients with type 2 diabetes , inadequately controlled on sitagliptin with or without metformin , add-on treatment with dapagliflozin provides additional clinical benefit and is well tolerated The UK Prospect i ve Diabetes Study ( UKPDS ) showed that a more intensive glucose control policy reduced risk of diabetic complications . As hypoglycemia is a barrier to achieving glycemic targets , we examined its occurrence and contributing factors in UKPDS patients r and omized to and remaining for 6 years on diet , sulfonylurea , metformin ( overweight subjects only ) , or insulin monotherapy from diagnosis of Type 2 diabetes . Self-reported hypoglycemic episodes were categorized as ( 1 ) transient , ( 2 ) temporarily incapacitated , ( 3 ) requiring third-party assistance , and ( 4 ) requiring medical attention , recording the most severe episode each quarter . Proportions of patients reporting at least one episode per year were calculated in relation to therapy , HbA(1c ) , and clinical characteristics . In 5063 patients aged 25 - 65 years , only 2.5 % per year reported substantive hypoglycemia ( Grade s 2 - 4 ) and 0.55 % major hypoglycemia ( Grade 3 or 4 ) . Hypoglycemia was more frequent in younger ( 4.0 % < 45 years vs. 2.2 % > or=45 years ) , female ( 3.0 % vs. 2.2 % male ) , normal weight ( 3.6 % body mass index < 25 kg/m(2 ) vs. 1.9 % > or=25 kg/m(2 ) ) , less hyperglycemic ( 5.2 % HbA(1c ) < 7 % vs. 2.3 % > or=7 % ) , or islet autoantibody-positive patients ( 4.3 % vs. 2.1 % negative ) ( all P<.0001 ) . More on basal insulin reported hypoglycemia ( 3.8 % per year ) than diet ( 0.1 % ) , sulfonylurea ( 1.2 % ) , or metformin ( 0.3 % ) therapy , but less than on basal and pr and ial insulin ( 5.3 % ) ( all P<.0001 ) . Low hypoglycemia rates seen during the first 6 years of intensive glucose lowering therapy in Type 2 diabetes are unlikely to have a major impact on attempts to achieve guideline glycemic targets when sulfonylurea , metformin , or insulin are used as monotherapy 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 Glucagon-like peptide 1 ( GLP-1 ) and analogues are being evaluated as a new therapeutic principle for the treatment of type 2 diabetes . GLP-1 suppresses glucagon secretion , which could lead to disturbances of hypoglycemia counterregulation . This has , however , not been tested . Nine healthy volunteers with normal oral glucose tolerance received infusions of regular insulin ( 1 mU x kg(-1 ) x min(-1 ) ) over 360 min on two occasions in the fasting state . Capillary glucose concentrations were clamped at plateaus of 4.3 , 3.7 , 3.0 , and 2.3 mmol/liter for 90 min each ( stepwise hypoglycemic clamp ) ; on one occasion , GLP-1 ( 1.2 pmol x kg(-1 ) x min(-1 ) ) was administered i.v . ( steady-state concentration , approximately 125 pmol/liter ) ; on the other occasion , NaCl was administered as placebo . Glucagon , cortisol , GH ( immunoassays ) , and catecholamines ( radioenzymatic assay ) were determined , autonomous and neuroglucopenic symptoms were assessed , and cognitive function was tested at each plateau . Insulin secretion rates were estimated by deconvolution ( two-compartment model of C-peptide kinetics ) . At insulin concentrations of approximately 45 mU/liter , glucose infusion rates were similar with and without GLP-1 ( P = 0.26 ) . Only during the euglycemic plateau ( 4.3 mmol/liter ) , GLP-1 suppressed glucagon concentrations ( 4.1 + /- 0.4 vs. 6.5 + /- 0.7 pmol/liter ; P = 0.012 ) ; at all hypoglycemic plateaus , glucagon increased similarly with GLP-1 or placebo , to maximum values greater than 20 pmol/liter ( P = 0.97 ) . The other counterregulatory hormones and autonomic or neuroglucopenic symptom scores increased , and cognitive functions decreased with decreasing glucose concentrations , but there were no significant differences comparing experiments with GLP-1 or placebo , except for a significant reduction of GH responses during hypoglycemia with GLP-1 ( P = 0.04 ) . GLP-1 stimulated insulin secretion only at plasma glucose concentrations of at least 4.3 mmol/liter . In conclusion , the suppression of glucagon by GLP-1 does occur at euglycemia , but not at hypoglycemic plasma glucose concentrations ( < or = 3.7 mmol/liter ) . GLP-1 does not impair overall hypoglycemia counterregulation except for a reduction in GH responses , which is in line with other findings demonstrating pituitary actions of GLP-1 . Below plasma glucose concentrations of 4.3 mmol/liter , the insulinotropic action of GLP-1 is negligible 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 The aim of this study was to evaluate the effects of exenatide on levels of serum adipocytokines and on β-cell function . The study was conducted between 2008 and 2012 . After a run-in period with metformin , 174 patients with type-2 diabetes were r and omly distributed to either a group receiving exenatide at 10 μg twice daily , or a group receiving the placebo , for 12 months . We evaluated body mass index ( BMI ) , blood pressure , glycemic control , lipid profile , fasting plasma insulin ( FPI ) , HOMA-IR , HOMA-β , fasting plasma proinsulin ( FPPr ) , proinsulin : fasting plasma insulin ratio ( Pr/FPI ratio ) , C-peptide , glucagon , retinol binding protein-4 ( RBP-4 ) , visfatin , omentin-1 , and microalbuminuria . We used ELISA methods to assess the various parameters . Patients also underwent a combined euglycemic-hyperinsulinemic and hyperglycemic clamp , with subsequent arginine stimulation . After 12 months , a combination of exenatide and metformin produced a better decrease in body mass , BMI , glycemic control , FPI , FPPr , FPPr/FPI ratio , HOMA-IR , and glucagon level . Treatment with exenatide + metformin was superior to the placebo + metformin in increasing HOMA-β , C-peptide , and β-cell function . Significant negative correlations were found between M value , an index of insulin sensitivity , and measured adipocytokines . In conclusion , the combination of exenatide + metformin plays a role in improving some adipocytokine levels , and is better than metformin alone . The significant negative correlation between M value and measured adipocytokines is another confirmation of the positive effects linked to the improvement in insulin sensitivity Introduction Ertugliflozin is an oral sodium-glucose cotransporter 2 inhibitor that is being developed to treat type 2 diabetes mellitus ( T2DM ) . This study assessed the efficacy and safety of co-initiation of ertugliflozin and sitagliptin compared with placebo in patients with T2DM inadequately controlled on diet and exercise . Methods In this phase III , r and omized , double-blind , multicenter , placebo-controlled 26-week study ( NCT02226003 ) , patients with T2DM and glycated hemoglobin ( HbA1c ) 8.0–10.5 % on diet/exercise were r and omized 1:1:1 to ertugliflozin 5 mg once daily ( QD ) and sitagliptin 100 mg QD ( E5/S100 ) , ertugliflozin 15 mg QD and sitagliptin 100 mg QD ( E15/S100 ) , or placebo . The primary efficacy endpoint was the change from baseline in HbA1c at week 26 . Results The mean baseline HbA1c of the r and omized patients ( n = 291 ) was 8.9 % . At week 26 , both ertugliflozin/sitagliptin treatments provided significant reductions from baseline in HbA1c compared with placebo [ least squares mean HbA1c change ( 95 % confidence intervals ) from baseline was − 0.4 % ( − 0.7 , − 0.2 ) , − 1.6 % ( − 1.8 , − 1.4 ) , and − 1.7 % ( − 1.9 , − 1.5 ) for placebo , E5/S100 , and E15/S100 , respectively ] . At week 26 , 8.3 % , 35.7 % , and 31.3 % of patients receiving placebo , E5/S100 , and E15/S100 , respectively , had HbA1c < 7.0 % . Significant reductions in fasting plasma glucose , 2-h post-pr and ial glucose , body weight , and systolic blood pressure were observed with both ertugliflozin/sitagliptin groups compared with placebo . The incidence of adverse events ( AEs ) was similar across the groups . The incidences of the pre-specified AEs of urinary tract infection , genital mycotic infection , symptomatic hypoglycemia , and hypovolemia were low and not meaningfully different across groups . Conclusion Co-initiation of ertugliflozin with sitagliptin in patients with T2DM inadequately controlled on diet and exercise provided a clinical ly meaningful improvement in glycemic control over 26 weeks . Clinical Trial Registration Clinical trials.gov NCT02226003 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 Aim Phase III , r and omized , double‐blind study evaluating the efficacy and safety of ertugliflozin in Asian patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled on metformin , including evaluation in the China sub population . Material s and methods A 26‐week , double‐blind study of 506 Asian patients ( 80.2 % from mainl and China ) , r and omized 1:1:1 to placebo , ertugliflozin 5‐ or 15 mg , was performed . Primary endpoint was change from baseline in HbA1c at week 26 . Secondary endpoints were change from baseline at week 26 in fasting plasma glucose ( FPG ) , body weight ( BW ) , systolic/diastolic blood pressure ( SBP/DBP ) , and proportion of patients with HbA1c < 7.0 % . Hypotheses for the primary endpoint and FPG and BW secondary endpoints were tested in the China sub population . Results At week 26 , least squares mean ( 95 % CI ) change from baseline HbA1c was significantly greater with ertugliflozin 5‐ and 15 mg versus placebo : −1.0 % ( −1.1 , −0.9 ) , −0.9 % ( −1.0 , −0.8 ) , −0.2 % ( −0.3 , −0.1 ) , respectively . Ertugliflozin significantly reduced FPG , BW and SBP . Reductions in DBP with ertugliflozin were not significant . At week 26 , 16.2 % , 38.2 % and 40.8 % of patients had HbA1c < 7.0 % with placebo , ertugliflozin 5‐ and 15 mg , respectively . 59.3 % , 56.5 % and 53.3 % of patients experienced adverse events with placebo , ertugliflozin 5‐ and 15 mg , respectively . Incidence of symptomatic hypoglycaemia was higher for ertugliflozin 15 mg vs placebo . Results in the China sub population were consistent . Conclusions Ertugliflozin significantly improved glycaemic control and reduced BW and SBP in Asian patients with T2DM . Ertugliflozin was generally well‐tolerated . Results in the China sub population were consistent with the overall population . Clinical Trials.gov : NCT02630706 AIM To evaluate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin plus metformin ( A + M ) initial combination therapy versus either as monotherapy in drug-naïve T2DM patients . METHODS This international , r and omized , double-blind , placebo-controlled , 26-week study involved T2DM patients with hyperglycaemia ( HbA1c 7.5 - 10.0 % ) following diet/exercise therapy . Patients ( N = 784 ) received placebo , alogliptin ( A , 12.5 mg BID or 25 mg QD ) , metformin ( M , 500 or 1000 mg BID ) or A + M ( 12.5/500 or 12.5/1000 mg BID ) ; placebo , A25 for secondary analyses only . ENDPOINTS week 26 changes from baseline in HbA1c ( primary ) , fasting plasma glucose ( FPG ) and 2-h postpr and ial glucose ( PPG ) ; incidences of clinical response and hyperglycaemic rescue . RESULTS Week 26 mean HbA1c reductions from baseline ( 8.45 % ) were -1.22 and -1.55 % with A + M 12.5/500 and 12.5/1000 versus -0.56 , -0.65 , and -1.11 % with A12.5 , M500 and M1000 ( p<0.001 , A + M vs. component monotherapies ) . FPG reductions were -1.76 and -2.55 mmol/L with 12.5/500 and 12.5/1000 versus -0.54 , -0.64 and -1.78 mmol/L with A12.5 , M500 and M1000 ( p < 0.05 , A + M vs. component monotherapies ) . Significantly more A + M-treated patients achieved HbA1c < 7 % ( 47.1 - 59.5 % vs. 20.2 - 34.3 % with monotherapy ) , significantly fewer required hyperglycaemic rescue ( 2.6 - 12.3 % vs. 10.8 - 22.9 % with monotherapy ) . A + M caused only mild/moderate hypoglycaemia ( 1.9 - 5.3 % ) and weight loss ( 0.6 - 1.2 kg ) . CONCLUSIONS Alogliptin plus metformin initial combination therapy was well tolerated yet more efficacious in controlling glycaemia in drug-naïve T2DM patients than either as monotherapy AIM This study was conducted to assess efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycaemia . METHODS Multicentre , double-blind , r and omized , placebo-controlled , parallel-group study of 52-week treatment with vildagliptin ( 50 mg q.d . ) in 306 drug-naïve patients with type 2 diabetes ( A1C = 6.2 - 7.5 % ) . A1C , fasting plasma glucose ( FPG ) and measures of pr and ial glucose control and beta-cell function determined during st and ard meal tests were assessed . RESULTS Baseline A1C and FPG averaged 6.7 % and 7.1 mmol/l , respectively , in patients r and omized to vildagliptin ( n = 156 ) and 6.8 % and 7.2 mmol/l in those r and omized to placebo ( n = 150 ) . A1C decreased modestly in vildagliptin-treated patients ( Delta = -0.2 + /- 0.1 % ) and increased in patients receiving placebo ( Delta = 0.1 + /- 0.1 % ) . The between-group difference ( vildagliptin - placebo ) in adjusted mean change ( AM Delta ) in A1C was -0.3 + /- 0.1 % ( p < 0.001 ) . FPG increased in patients receiving placebo ( Delta = 0.5 + /- 0.1 mmol/l ) and to a significantly lesser extent in vildagliptin-treated patients ( between-group difference in AM Delta FPG = -0.4 + /- 0.2 mmol/l , p = 0.032 ) . Relative to placebo , 2-h postpr and ial glucose ( PPG ) decreased ( -0.9 + /- 0.4 mmol/l , p = 0.012 ) , and insulin secretory rate ( ISR ) relative to glucose [ ISR area under the curve (AUC)(0 - 2 ) (h)/glucose AUC(0 - 2 ) ( h ) ] increased ( + 5.0 + /- 1.2 pmol/min/m(2)/mM , p < 0.001 ) . Mean body weight decreased by 0.5 + /- 0.3 kg in vildagliptin-treated patients and by 0.2 + /- 0.3 kg in patients receiving placebo . The side-effect profile of vildagliptin was similar to that of placebo , and one hypoglycaemic episode occurred in one patient receiving placebo . CONCLUSIONS In drug-naïve patients with mild hyperglycaemia , relative to placebo , 52-week treatment with vildagliptin 50 mg q.d . significantly decreases A1C , FPG and PPG and improves beta-cell function without weight gain or hypoglycaemia AIMS Evaluate dose-dependent effects of once-weekly dulaglutide , a glucagon-like peptide-1 analogue , on glycaemic control in patients with Type 2 diabetes treated with lifestyle measures with or without previous metformin . METHODS This 12-week , double-blind , placebo-controlled , dose-response trial r and omized 167 patients who were anti-hyperglycaemic medication-naïve or had discontinued metformin monotherapy [ mean baseline HbA(1c ) 59 ± 8 to 61 ± 8 mmol/mol ( 7.6 ± 0.7 to 7.8 ± 0.8 % ) ] to once-weekly injections of placebo or dulaglutide ( 0.1 , 0.5 , 1.0 or 1.5 mg ) . RESULTS A significant dose-dependent reduction in HbA(1c ) ( least squares mean ± SE ) was observed across doses ( P < 0.001 ) . HbA(1c ) reductions in the 0.5 , 1.0 and 1.5 mg dulaglutide groups were greater than in the placebo group [ -10 ± 1 , -11 ± 1 and -11 ± 1 vs. 0 ± 1 mmol/mol ( -0.9 ± 0.1 , -1.0 ± 0.1 and -1.0 ± 0.1 vs. 0.0 ± 0.1 % ) , respectively , all P < 0.001 ] . Dose-dependent reductions in fasting plasma glucose were also observed [ least squares mean difference ( 95 % CI ) ranging from -0.43 ( -1.06 to 0.19 ) mmol/l for dulaglutide 0.1 mg to -1.87 ( -2.56 to -1.19 ) mmol/l for dulaglutide 1.5 mg , P < 0.001 ] . Dose-dependent weight loss was demonstrated across doses ( P = 0.009 ) , but none of the groups were different from placebo . The most common adverse events were nausea and diarrhoea . CONCLUSIONS The observed dulaglutide dose-dependent reduction in HbA(1c ) and its acceptable safety profile support further clinical development for treatment of Type 2 diabetes ABSTRACT Objective : The study investigated the efficacy and tolerability of teneligliptin co-administered to patients with type 2 diabetes mellitus ( T2DM ) who were inadequately controlled by stable metformin monotherapy ≥ 1000 mg/day . Methods : A total of 447 patients from 55 European centers who completed a 14-day screening and 14-day run-in phase , received r and omized double-blind treatment with 5 , 10 , 20 or 40 mg teneligliptin or placebo once daily , for 24 weeks . 364 patients continued treatment in a 28-week open label extension during which they received teneligliptin 20 mg once daily . Results : Co-administration of teneligliptin ( 5 to 40 mg ) with metformin demonstrated dose-related and statistically significant reductions in HbA1c after 24 weeks ( -0.30 to -0.63 % placebo adjusted ) of double-blind treatment . The greatest reduction in HbA1c was seen with teneligliptin at 40 mg ( -0.63 % ) at Week 24 . There was also a dose-dependent increase in proportion of responders achieving HbA1c < 7.0 % at this endpoint . Responses were maintained throughout 28 weeks open label treatment with 20 mg teneligliptin . Treatment was well tolerated to Week 52 and the overall incidence of hypoglycemia during 52 weeks was 2.3 % . Conclusions : Teneligliptin co-administered with metformin produced significant reductions in HbA1c in patients with T2DM without increasing the risk of hypoglycemia 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 Abstract Objective : To investigate the optimal dosage/regimen and to evaluate the efficacy and safety of albiglutide in Japanese patients with type 2 diabetes mellitus . Research design and methods : This was a r and omized , double-blind , placebo-controlled , multicenter , parallel-group , dose-ranging , superiority study in Japanese patients with type 2 diabetes mellitus . Patients ( n = 215 ) who were treatment naive or washed out of one oral antidiabetic drug were r and omized to placebo or albiglutide 15 mg weekly , 30 mg weekly , or 30 mg every other week ( biweekly ) . Clinical trial registration : NCT01098461 . Main outcome measures : The primary end point was the change from baseline in HbA1c at week 16 , measured using the Japan Diabetes Society st and ardization scheme and presented here using the National Glycohemoglobin St and ardization Program equivalents . Other measures of efficacy as well as safety and population pharmacokinetics and pharmacokinetics/pharmacodynamics of albiglutide were assessed . Results : Baseline HbA1c was 8.53 % . There was a statistically significant difference between each albiglutide treatment group and placebo for change from baseline in HbA1c at week 16 , with treatment effects of −0.89 % for 15 mg weekly , −1.55 % for 30 mg weekly , and −1.10 % for 30 mg biweekly ( P < 0.0001 for all groups vs placebo ) . By week 16 , 63.0 % and 33.3 % of patients in the 30 mg weekly albiglutide group compared with 6.0 % and 0 % of patients in the placebo group achieved HbA1c < 7.4 % and < 6.9 % , respectively . No serious adverse events were related to study therapy ; no deaths occurred . Nasopharyngitis was the most frequently reported adverse event in all treatment groups ( n = 43 [ 20.3 % ] ) . Conclusions : Albiglutide exhibited therapeutic hypoglycemic effects with good tolerability among Japanese patients with type 2 diabetes mellitus ; the 30 mg weekly dose was the most efficacious in this study . The 16 week duration of the study prevents generalizing these conclusions to longer treatment periods OBJECTIVE To compare the efficacy and safety of treatment with dapagliflozin versus that with placebo add-on to saxagliptin plus metformin in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin treatment . RESEARCH DESIGN AND METHODS Patients receiving treatment with stable metformin ( stratum A ) ( screening HbA1c level 8.0–11.5 % [ 64–102 mmol/mol ] ) or stable metformin and a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor ( stratum B ) ( HbA1c 7.5–10.5 % [ 58–91 mmol/mol ] ) for ≥8 weeks received open-label saxagliptin 5 mg/day and metformin for 16 weeks ( stratum A ) or 8 weeks ( stratum B ) ( saxagliptin replaced any DPP-4 inhibitor ) . Patients with inadequate glycemic control ( HbA1c 7–10.5 % [ 53–91 mmol/mol ] ) were r and omized to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin . The primary end point was the change in HbA1c from baseline to week 24 . Secondary end points included fasting plasma glucose ( FPG ) level , 2-h postpr and ial glucose ( PPG ) level , body weight , and proportion of patients achieving an HbA1c level of < 7 % ( 53 mmol/mol ) . RESULTS Treatment with dapagliflozin add-on to saxagliptin plus metformin result ed in a greater mean HbA1c reduction than placebo ( −0.82 vs. −0.10 % [ −9 vs. −1.1 mmol/mol ] , P < 0.0001 ) . Significantly greater reductions in FPG level , 2-h PPG level , and body weight were observed , and more patients achieved an HbA1c level of < 7 % ( 53 mmol/mol ) with treatment with dapagliflozin versus placebo . Adverse events were similar across treatment groups , with a low overall risk of hypoglycemia ( ∼1 % ) . Genital infections developed in more patients with dapagliflozin treatment ( 5 % ) than with placebo ( 0.6 % ) . CONCLUSIONS Triple therapy with dapagliflozin add-on to saxagliptin plus metformin improves glycemic control and is well tolerated in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin therapy 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 OBJECTIVE To evaluate the efficacy and safety of empagliflozin versus placebo as add-on therapy in patients with type 2 diabetes and inadequate glycemic control with linagliptin and metformin . RESEARCH DESIGN AND METHODS Patients with HbA1c ≥8.0 % and ≤10.5 % ( ≥64 and ≤91 mmol/mol ) while receiving stable-dose metformin received open-label linagliptin 5 mg ( n = 606 ) for 16 weeks . Subsequently , those with HbA1c ≥7.0 and ≤10.5 % ( ≥53 and ≤91 mmol/mol ) were r and omized to receive double-blind , double-dummy treatment with empagliflozin 10 mg ( n = 112 ) , empagliflozin 25 mg ( n = 111 ) , or placebo ( n = 110 ) for 24 weeks ; all patients continued treatment with metformin and linagliptin 5 mg . The primary end point was the change from baseline in HbA1c after 24 weeks of double-blind treatment . RESULTS At week 24 , empagliflozin significantly reduced HbA1c ( mean baseline 7.96–7.97 % [ 63–64 mmol/mol ] ) versus placebo ; the adjusted mean differences in the change from baseline with empagliflozin 10 and 25 mg versus placebo were −0.79 % ( 95 % CI ‒1.02 , ‒0.55 ) ( −8.63 mmol/mol [ ‒11.20 , ‒6.07 mmol/mol ] ) and −0.70 % ( 95 % CI ‒0.93 , ‒0.46 ) ( −7.61 mmol/mol [ ‒10.18 , ‒5.05 mmol/mol ] ) , respectively ( both P < 0.001 ) . Fasting plasma glucose and weight were significantly reduced in both empagliflozin groups versus placebo ( P < 0.001 for all comparisons ) . More patients receiving placebo than empagliflozin 10 and 25 mg reported adverse events during double-blind treatment ( 68.2 % , 55.4 % , and 51.8 % , respectively ) . CONCLUSIONS Empagliflozin treatment for 24 weeks improved glycemic control and weight versus placebo as an add-on to linagliptin 5 mg and metformin and was well tolerated OBJECTIVE To investigate the efficacy and safety of once-daily semaglutide in comparison with once-daily liraglutide and placebo in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS This 26-week , multicenter , double-blind trial involved patients diagnosed with type 2 diabetes with HbA1c 7.0–10.0 % ( 53–86 mmol/mol ) and treated with diet and exercise with or without metformin . Patients were r and omized 2:2:1 to once-daily semaglutide , liraglutide , or placebo in one of four volume-matched doses ( semaglutide 0.05 , 0.1 , 0.2 , or 0.3 mg and liraglutide 0.3 , 0.6 , 1.2 , or 1.8 mg , with both compared within each volume-matched dose group ) . Primary end point was change in HbA1c from baseline to week 26 . RESULTS In total , 705 r and omized patients were exposed to trial products . At week 26 , a dose-dependent change in HbA1c was observed with semaglutide from −1.1 % ( 0.05 mg ) to −1.9 % ( 0.3 mg ) and with liraglutide from −0.5 % ( 0.3 mg ) to −1.3 % ( 1.8 mg ) ( all P < 0.001 in favor of volume-matched semaglutide dose ) . Change with pooled placebo was −0.02 % ( P < 0.0001 vs. semaglutide ) . Gastrointestinal ( GI ) disorders were the most common adverse events ( AEs ) with semaglutide and liraglutide , occurring in 32.8–54.0 % and 21.9–41.5 % of patients , respectively . CONCLUSIONS Once-daily semaglutide at doses up to 0.3 mg/day result ed in greater reductions in HbA1c compared with liraglutide or placebo but with a higher frequency of GI AEs |
10,302 | 31,830,124 | This systematic review gathered evidence from Denmark and Switzerl and on barriers and facilitators concerning data harmonization , sharing and linkage .
Barriers and facilitators were strictly interrelated with the national context where projects were carried out .
Structural changes , such as legislation implemented at the national level , were mirrored in the projects .
This underlines the impact of national strategies in the field of health data . | INTRODUCTION The digitalization of medicine has led to a considerable growth of heterogeneous health data sets , which could improve healthcare research if integrated into the clinical life cycle .
This process requires , amongst other things , the harmonization of these data sets , which is a prerequisite to improve their quality , re-usability and interoperability .
However , there is a wide range of factors that either hinder or favor the harmonized collection , sharing and linkage of health data .
OBJECTIVE This systematic review aims to identify barriers and facilitators to health data harmonization-including data sharing and linkage-by a comparative analysis of studies from Denmark and Switzerl and . | Background Non-steroid anti-inflammatory drugs ( NSAIDs ) have been proposed as part of a multimodal postoperative analgesia in patients operated for colorectal cancer . However , whether these drugs are prescribed and taken by the patients have not been evaluated . The aim of this study was to quantify the postoperative use of NSAIDs in these patients . Methods Data from patients operated for colorectal cancer between January 1 , 2006 and December 31 , 2009 were collected from the Danish Colorectal Cancer Group ’s ( DCCG ) prospect i ve data base . From the electronically registered medical records , data for the use of the two NSAIDs diclofenac and ibuprofen were recorded . The data from six colorectal departments in eastern Denmark were compared . Results Of the 2,754 patients analyzed overall , 40.6 % received NSAIDs as part of their analgesic treatment . The percentage of the patients receiving NSAIDs , receiving a pre-defined dosage as a minimum and receiving NSAIDs as p.r.n . medication , and the type of NSAID were significantly different both between department and within departments . The median dose of ibuprofen and diclofenac were 1200 mg ( 400–2,400 mg ) and 100 mg ( 50–200 mg ) , respectively . Conclusions The large variation between and within the departments points to an inconsistency in the use of multimodal post-operative pain treatments . This may be a result of insufficient evidence on procedure specific pain treatments and possibly a lack of compliance to existing guidelines . High- quality large-scale studies are warranted to form the basis for guidelines for postoperative analgesic treatment We hypothesize that perinatal exposures , in particular the human microbiome and maternal nutrition during pregnancy , interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others Background : The Western Denmark Heart Registry ( WDHR ) has not previously been described as a research tool in clinical epidemiology . Objectives : We examined the setting , organization , content , data quality , and research potential of the WDHR . Method : We collected information from members of the WDHR organization , including the committee of representatives , the board , the data management group , and physicians reporting to the data base . We retrieved 2008 data from the WDHR to illustrate data base variables . Results : The WDHR is a clinical data base within a population -based health care system . It was launched on 1 January 1999 to monitor and improve the quality of cardiac intervention in Western Denmark ( population : 3.3 million ) and to allow for clinical and health-service research . More than 200,000 interventions , with 50–150 variables each , have been registered . The data quality is ensured by automatic validation rules at data entry combined with systematic validation procedures and r and om spot-checks after entry . Conclusions : The WDHR is a valuable research tool because it provides ongoing longitudinal registration of detailed patient and procedural data . The Danish national health care system enables this research because it allows complete follow-up for medical events after cardiac intervention by linkage with multiple medical data bases Background Glycaemia control ( GC ) remains an important therapeutic goal in critically ill patients . The enhanced Model Predictive Control ( eMPC ) algorithm , which models the behaviour of blood glucose ( BG ) and insulin sensitivity in individual ICU patients with variable blood sample s , is an effective , clinical ly proven computer based protocol successfully tested at multiple institutions on medical and surgical patients with different nutritional protocol s. eMPC has been integrated into the B.Braun Space GlucoseControl system ( SGC ) , which allows direct data communication between pumps and microprocessor . The present study was undertaken to assess the clinical performance and safety of the SGC for glycaemia control in critically ill patients under routine conditions in different ICU setting s and with various nutritional protocol s. Methods The study endpoints were the percentage of time the BG was within the target range 4.4 – 8.3 mmol.l−1 , the frequency of hypoglycaemic episodes , adherence to the advice of the SGC and BG measurement intervals . BG was monitored , and insulin was given as a continuous infusion according to the advice of the SGC . Nutritional management ( enteral , parenteral or both ) was carried out at the discretion of each centre . Results 17 centres from 9 European countries included a total of 508 patients , the median study time was 2.9 ( 1.9 - 6.1 ) days . The median ( IQR ) time – in – target was 83.0 ( 68.7 - 93.1 ) % of time with the mean proposed measurement interval 2.0 ± 0.5 hours . 99.6 % of the SGC advices on insulin infusion rate were accepted by the user . Only 4 episodes ( 0.01 % of all BG measurements ) of severe hypoglycaemia < 2.2 mmol.l−1 in 4 patients occurred ( 0.8 % ; 95 % CI 0.02 - 1.6 % ) . Conclusion Under routine conditions and under different nutritional protocol s the Space GlucoseControl system with integrated eMPC algorithm has exhibited its suitability for glycaemia control in critically ill patients .Trial registration Clinical Trials.gov Background Percutaneous mitral valve repair ( MVR ) using the MitraClip system has become a valid alternative for patients with severe mitral regurgitation ( MR ) and high operative risk . Objective To identify clinical and periprocedural factors that may have an impact on clinical outcome . Design Multi-centre longitudinal cohort study . Setting Tertiary referral centres . Patients Here we report on the first 100 consecutive patients treated with percutaneous MVR in Switzerl and between March 2009 and April 2011 . All of them had moderate – severe ( 3 + ) or severe ( 4 + ) MR , and 62 % had functional MR . 82 % of the patients were in New York Heart Association ( NYHA ) class III/IV , mean left ventricular ejection fraction was 48 % and the median European System for Cardiac Operative Risk Evaluation was 16.9 % . Interventions MitraClip implantation performed under echocardiographic and fluoroscopic guidance in general anaesthesia . Main outcome measures Clinical , echocardiographic and procedural data were prospect ively collected . Results Acute procedural success ( APS , defined as successful clip implantation with residual MR grade ≤2 + ) was achieved in 85 % of patients . Overall survival at 6 and 12 months was 89.9 % ( 95 % CI 81.8 to 94.6 ) and 84.6 % ( 95 % CI 74.7 to 91.0 ) , respectively . Univariate Cox regression analysis identified APS ( p=0.0069 ) and discharge MR grade ( p=0.03 ) as significant predictors of survival . Conclusions In our consecutive cohort of patients , APS was achieved in 85 % . APS and residual discharge MR grade are important predictors of mid-term survival after percutaneous MVR Background Long-term mortality and causes of death in patients with pulmonary tuberculosis ( PTB ) and extrapulmonary tuberculosis ( EPTB ) are poorly documented . In this study , long-term mortality and causes of death in PTB and EPTB patients were compared with the background population and it was investigated whether mortality was associated with family-related risk factors . Methods A nationwide cohort study was conducted including : all adult Danes notified with PTB or EPTB from 1977 to 2008 and alive 1 year after diagnosis ; a r and omly selected comparison cohort matched on birth date and sex ; adult siblings of PTB patients ; and population controls . Data were extracted from national registries . All-cause and cause-specific mortality rate ratios were calculated for patients and siblings and compared with their respective control cohorts . A total of 8,291 patients ( 6,402 PTB and 1,889 EPTB ) , 24,873 population controls , 1,990 siblings of PTB patients and 11,679 siblings of PTB population controls were included . Results Overall , the mortality rate ratio was 1.86 ( 95 % confidence interval [ CI ] 1.77–1.96 ) for PTB patients and 1.24 ( 95 % CI 1.12–1.37 ) for EPTB patients . Both patient cohorts had significantly increased risk of death due to infectious diseases and diabetes . Further , the PTB patients had increased mortality due to cancers ( mainly respiratory and gastrointestinal tract ) , liver and respiratory system diseases , and alcohol and drug abuse . The PTB patients had increased mortality compared with their siblings ( mortality rate ratio 3.55 ; 95 % CI 2.57–4.91 ) as did the siblings of the PTB patients compared with the siblings of population controls ( mortality rate ratio 2.16 ; 95 % CI 1.62–2.87 ) . Conclusion We conclude that adult PTB patients have an almost two-fold increased long-term mortality whereas EPTB patients have a slightly increased long-term mortality compared with the background population . The increased long-term mortality in PTB patients stems from diseases associated with alcohol , tobacco , and drug abuse as well as immune suppression , and family-related factors Background Patient-self-management ( PSM ) of oral anticoagulant therapy with vitamin K antagonists has demonstrated efficacy in r and omized , controlled trials . However , the effectiveness and efficacy of PSM in clinical practice and whether outcomes are different for females and males has been sparsely investigated . The objective is to evaluate the sex-dependent effectiveness of PSM of oral anticoagulant therapy in everyday clinical practice . Methods All patients performing PSM affiliated to Aarhus University Hospital and Aalborg University Hospital , Denmark in the period 1996–2012 were included in a case-series study . The effectiveness was estimated using the following parameters : stroke , systemic embolism , major bleeding , intracranial bleeding , gastrointestinal bleeding , death and time spent in the therapeutic international normalized ratio ( INR ) target range . Prospect ively registered patient data were obtained from two data bases in the two hospitals . Cross-linkage between the data bases and national registries provided detailed information on the incidence of death , bleeding and thromboembolism on an individual level . Results A total of 2068 patients were included , representing 6,900 patient-years in total . Males achieved a significantly better therapeutic INR control than females ; females spent 71.1 % of the time within therapeutic INR target range , whereas males spent 76.4 % ( p<0.0001 ) . Importantly , death , bleeding and thromboembolism were not significantly different between females and males . Conclusions Among patients treated with self-managed oral anticoagulant therapy , males achieve a higher effectiveness than females in terms of time spent in therapeutic INR range , but the incidence of major complications is low and similar in both sexes Background and Purpose — Although secondary medical prevention strategies in patients with stroke are well established , only sparse data exist regarding their effectiveness in routine care . We examined the effectiveness in a nationwide , population -based follow-up study . Methods — Using data from the Danish National Indicator Project ( DNIP ) , 28 612 patients hospitalized for ischemic stroke in 2003 to 2006 were identified . Information on drug use and outcomes was by individual-level record linkage with national medical data bases . Hazard ratios were computed for death , myocardial infa rct ion , and recurrent stroke according to drug use after hospital discharge . Results — Treatment with antiplatelets , oral anticoagulants , antihypertensives , or statins was associated with a lower risk of the combined end point of death , myocardial infa rct ion , or recurrent stroke during a mean follow-up period of 2.7 years ( adjusted hazard ratios [ HRs ] from 0.44 [ 95 % CI , 0.39–0.49 ] to 0.94 [ 95 % CI , 0.89–0.99 ] ) . All drug classes were associated with lower risk of death ( adjusted HRs from 0.36 [ 95 % CI , 0.32–0.41 ] to 0.85 [ 95 % CI , 0.80–0.90 ] ) , with oral anticoagulant treatment in patients with atrial fibrillation being particularly effective in elderly women ( > 80 years ; adjusted HR , 0.35 ; 95 % CI , 0.28–0.45 ) . Oral anticoagulant treatment was associated with a lower risk of recurrent stroke ( adjusted HR , 0.58 ; 95 % CI , 0.47–0.73 ) , and statins were associated with a lower risk of myocardial infa rct ion ( adjusted HR , 0.84 ; 95 % CI , 0.73–0.97 ) and recurrent stroke ( adjusted HR , 0.86 ; 95 % CI , 0.79–0.92 ) . Conclusions — Secondary medical prophylaxis after ischemic stroke was associated with improved outcome in routine setting s. Although these findings are of an observational nature , they tend to support the results from previous r and omized trials Objective Patient ’s language , tradition , conventions , and customs may all determine integration into a society and are also part of the doctor – patient relationship that influences diagnostic and therapeutic outcome . Language barrier and sociocultural disparity of Eastern and Southern European patients may hamper recovery from pain and depression compared to Middle European patients in Switzerl and . Methods In a prospect i ve naturalistic observational trial we investigated the influence of regional origin on treatment outcome in 420 pain sufferers with depressive symptoms from all over Switzerl and who were treated with venlafaxine by 122 physicians in primary care . Physicians rated severity of depressive symptoms using the clinical global impression severity scale and pain intensity by means of visual analogue scales . We hypothesized that in Eastern and Southern European patients the magnitude of pain reduction under treatment with venlafaxine is less compared to Middle European patients . Results Three months after study entry , Middle European patients were found to profit more from treatment with venlafaxine in terms of severity of depression and pain intensity than patients from Eastern Europe and Southern Europe . Conclusion Regional origin may contribute to the magnitude of pain reduction in patients with depressive symptoms under treatment with venlafaxine . Our results provide a rational for care provider educational programs aim ed at improving capacities in treating patients from different regional origin with psychosomatic complaints such as depression and comorbid pain INTRODUCTION Complications to oesophageal and junctional cancer surgery are common and have not diminished much during the past ten years . An unusually high occurrence of anastomotic dehiscence occurred in Denmark in 2009 and 2010 as seen in the national data base for oesophagus , cardiac and gastric ( ECV ) cancer . MATERIAL AND METHODS In accordance with national guidelines , all patients resected for oesophageal and junctional cancer in Denmark from 2003 were prospect ively entered into a national data base . Data concerning anaesthesia , peri- and post-operative course , complications , re-operations and time spent in intensive care unit were obtained retrospectively from hospital records . An in-depth analysis of data from two high-volume centres performing ECV cancer surgery according to national guidelines was performed . RESULTS A total of 881 patients ( Centre 1 : 438 ; Centre 2 : 443 ) were resected for oesophageal and junctional cancer . A total of 79 patients with anastomotic insufficiency ( AI ) were detected ( Centre 1 : 36 ; Centre 2 : 43 ) . By using a grading system , it was shown that AI was more severe and occurred earlier in one centre than in the other . Possible factors of influence are discussed , including neoadjuvant oncological therapy , use of thoracoscopically performed anastomosis and perioperative inotrophic drugs . CONCLUSION Thanks to the establishment of a nationwide data base in pursuance of national guidelines , it was possible to detect variations in quality of surgery over time , evaluate serious complications early and undertake an in-depth analysis of possible aetiological factors . Particularly , comparison was facilitated by the use of a st and ardised grading system for complications . FUNDING not relevant . TRIAL REGISTRATION not relevant AIMS of AMIS Plus To learn from each other , to underst and the transfer , use and practicability of knowledge gained from r and omised trials and to generate input for subsequent prospect i ve and r and omised studies . Furthermore , to determine how adherence to guideline -based treatments in the ‘ real world ’ works . Funding AMIS Plus is an industry-sponsored project but the supporting institutions do not play any part in the design of the registry , data collection , analysis or interpretation . Quality -of-care interventions AMIS Plus data enable doctors to identify deficits in medical care , implement the necessary changes in diagnostics and therapeutic procedures and document their impact on clinical outcome in patients with acute coronary syndrome ( ACS ) . Setting From 106 hospitals treating ACS in Switzerl and , 76 hospitals temporarily or continuously enrolled patients in AMIS Plus . Years : 1997– Population Patients are included on the basis of their final diagnosis . Current number of cases : 33 040 . Start points ST elevation myocardial infa rct ion , non-ST elevation myocardial infa rct ion and since 2000 , unstable angina . Baseline data 230 variables are collected including demographics , medical history , cardiovascular risk factors , acute symptoms , time of symptom onset , first medical contact , time of admission and start of thrombolysis or balloon , out of hospital management , clinical presentation , early in-hospital management , reperfusion treatment , hospital course , diagnostic tests used or planned , hospital length of stay , discharge medication , destination and at 1 year , outcome , rehospitalisation , intervention , working time and quality of daily life . Data capture Data are provided through an internet- or paper-based question naire completed by the treating doctor or a trained study nurse . Data quality The data are central ised at the AMIS Plus Data Center , checked for plausibility and consistency and crosschecked when queries arise . Incomplete question naires are returned to the enrolment centres for completion . One-third of the variables are obligatory . End point and linkages to other data In-hospital outcome , 3-months and 1-year follow-up outcome . No linkages exist at present . Access to data Available for research with the approval of the AMIS Plus Steering Committee . Participating hospitals use the data for benchmarking and their own quality control Background Danish patients with musculoskeletal disorders are commonly referred for primary care physiotherapy treatment but little is known about their general health status , pain diagnoses , clinical course and prognosis . The objectives of this study were to 1 ) describe the clinical course of patients with musculoskeletal disorders referred to physiotherapy , 2 ) identify predictors associated with a satisfactory outcome , and 3 ) determine the influence of the primary pain site diagnosis relative to those predictors . Methods This was a prospect i ve cohort study of patients ( n = 2,706 ) newly referred because of musculoskeletal pain to 30 physiotherapy practice s from January 2012 to May 2012 . Data were collected via a web-based question naire 1–2 days prior to the first physiotherapy consultation and at 6 weeks , 3 and 6 months , from clinical records ( including primary musculoskeletal symptom diagnosis based on the ICPC-2 classification system ) , and from national registry data . The main outcome was the Patient Acceptable Symptom State . Potential predictors were analysed using backwards step-wise selection during longitudinal Generalised Estimating Equation regression modelling . To assess the influence of pain site on these associations , primary pain site diagnosis was added to the model . Results Of the patients included , 66 % were female and the mean age was 48 ( SD 15 ) . The percentage of patients reporting their symptoms as acceptable was 32 % at 6 weeks , 43 % at 3 months and 52 % at 6 months . A higher probability of satisfactory outcome was associated with place of residence , being retired , no compensation cl aim , less frequent pain , shorter duration of pain , lower levels of disability and fear avoidance , better mental health and being a non-smoker . Primary pain site diagnosis had little influence on these associations , and was not predictive of a satisfactory outcome . Conclusion Only half of the patients rated their symptoms as acceptable at 6 months . Although satisfactory outcome was difficult to predict at an individual patient level , there were a number of prognostic factors that were associated with this outcome . These factors should be considered when developing generic prediction tools to assess the probability of satisfactory outcome in musculoskeletal physiotherapy patients , because the site of pain did not affect that prognostic association Background Adherence to guidelines is associated with improved outcomes of patients with acute coronary syndrome ( ACS ) . Clinical registries developed to assess quality of care at discharge often do not collect the reasons for non-prescription for proven efficacious preventive medication in Continental Europe . In a prospect i ve cohort of patients hospitalized for an ACS , we aim ed at measuring the rate of recommended treatment at discharge , using pre-specified quality indicators recommended in cardiologic guidelines and including systematic collection of reasons for non-prescription for preventive medications . Methods In a prospect i ve cohort with 1260 patients hospitalized for ACS , we measured the rate of recommended treatment at discharge in 4 academic centers in Switzerl and . Performance measures for medication at discharge were pre-specified according to guidelines , systematic ally collected for all patients and included in a central ized data base . Results Six hundred and eighty eight patients ( 54.6 % ) were discharged with a main diagnosis of STEMI , 491(39 % ) of NSTEMI and 81(6.4 % ) of unstable angina . Mean age was 64 years and 21.3 % were women . 94.6 % were prescribed angiotensin converting enzyme inhibitors/angiotensin II receptor blockers at discharge when only considering raw prescription rates , but increased to 99.5 % when including reasons non-prescription . For statins , rates increased from 98 % to 98.6 % when including reasons for non-prescription and for beta-blockers , from 82 % to 93 % . For aspirin , rates further increased from 99.4 % to 100 % and from to 99.8 % to 100 % for P2Y12 inhibitors . Conclusions We found a very high adherence to ACS guidelines for drug prescriptions at discharge when including reasons for non-prescription to drug therapy . For beta-blockers , prescription rates were suboptimal , even after taking into account reason for non-prescription . In an era of improving quality of care to achieve 100 % prescription rates at discharge unless contra-indicated , pre-specification of reasons for non-prescription for cardiovascular preventive medication permits to identify remaining gaps in quality of care at discharge . Trial Registration Clinical Trials.gov No data on primary biliary cholangitis ( PBC ) are available in Switzerl and . We established a national patient cohort to obtain information on PBC phenotypes and disease course in Switzerl and . Local data bases in all university hospitals and in two large secondary centers were search ed for case finding . In addition , all primary care physicians , gastroenterologists , rheumatologists , and dermatologists were invited to contribute patients from their own medical records . PBC diagnosis was central ly review ed . Five hundred one PBC patients were identified , 474 were included in data analysis , and 449 of them were enrolled by tertiary centers . The catchment area accounts for approximately one third of the Swiss population or approximately 2.8 million inhabitants . The median age at diagnosis was 53 years , 84 % were women , and 86 % were anti-mitochondrial antibody positive . The median follow-up was 5.4 years , 12.6 % experienced a liver-related endpoint . Splenomegaly was present at diagnosis in one quarter of patients and in half of male patients . Approximately one third were non-responders to ursodeoxycholic acid ( UDCA ) . The median transplant-free survival at 10 years was 85 % . The following variables were independently associated with poor outcome : low platelet count at baseline ( HR = 0.99 , p < 0.0001 ) , elevated alkaline phosphatase at baseline ( HR = 1.36 , p < 0.0001 ) , elevated bilirubin at baseline ( HR = 1.11 , p = 0.001 ) , and elevated alanine aminotransaminase ( HR = 1.35 , p = 0.04 ) after 12 months of UDCA therapy . The AUROC for the UK-PBC risk score at 5 , 10 , and 15 years was 0.82 . The AUROC for the Globe score at 5 , 10 , and 15 years was 0.77 . Patients included in this study are currently being enrolled in a prospect i ve nationwide registry with biobank , taking advantage of the collaboration network generated by this study . Our study provides the first snapshot of PBC in Switzerl and , describing a diagnostic delay with one quarter of patients diagnosed when already in the cirrhotic stage . We were also able to externally vali date the UK-PBC risk score and the Globe score . The ongoing nationwide prospect i ve registry will be fundamental to improve disease awareness and interdisciplinary collaborations and will serve as a platform for clinical and translational research .Trial registration number : clinical trials.gov : NCT02846896 ; DBCG ( Danish Breast Cancer Cooperative Group ) constitutes a multidisciplinary organization established in 1975 by the Danish Surgical Society . The purpose involves first and foremost a nation-wide st and ardization of breast cancer treatment based on novel therapeutic principles , collaboration between experts h and ling diagnostic work-up , surgery , radiotherapy , medical oncology , and basic research , and , further , complete registration of relevant clinical data in a national data base attached to DBCG . Data are processed by the Secretariat personnel composed of statisticians , data managers , and data secretaries making current analyses of outcome results feasible . DBCG is run by the Executive Committee consisting of expert members appointed by their respective society . From 1978 the DBCG project gained widely accession from participating units , and since then nearly all newly diagnosed breast cancer incident cases are reported and registered in the national data base . Today , the data base includes approximately 80 000 incidents of primary breast cancer . Annually , the Secretariat receives roughly 1.5 million parameters to be entered into the data base . Over time DBCG has generated seven treatment programmes including in situ lesions and primary invasive breast cancer . Prob and s are subdivided into risk groups based on a given risk pattern and allocated to various treatment programmes accordingly . The scientific initiatives are conducted in the form of register- and cohort analysis or r and omized trials in national or international protocol ized setting s. Yearly , about 4 000 new incident cases of primary invasive breast cancer and about 200 in situ lesions enter the national programmes . Further , about 600 women with hereditary disposition of breast cancer are registered and evaluated on a risk scale . The main achievements result ed in a reduction of relative risk of death amounting up to 20 % and increased 5-year overall survival ascending from 60 % to roughly 80 % . This article is partly based on a Danish paper to be published in the Centenary Jubilee book of the Danish Surgical Society , 2008 BACKGROUND Vascular access complications after coronary angiography ( CAG ) and percutaneous coronary intervention ( PCI ) are known to increase morbidity , prolong hospitalization and raise hospital costs . Therefore , risk factor identification and improvement of safety strategies for vascular management are important . We aim ed to assess the incidence of major vascular complications related to femoral access , and to identify potential risk factors . METHODS Over a period of six years , 23,870 index procedures ( CAG ) were performed in two centres , prospect ively entered in the data base and retrospectively analysed . Data was obtained from the Eastern Danish Heart Registry and cross-matched with data from the Danish Vascular Registry . Index procedures were defined as the first trans-femoral procedure . Demographic , procedural and mortality data , as well as information on access complications requiring surgery within 30 days were collected . Mortality data were collected for minimum 12 months . RESULTS We identified 130 ( 0.54 % ) access complications requiring surgery ; 65 pseudoaneurysms ( 0.28 % ) , 46 arterial occlusions ( 0.19 % ) , 15 hematomas ( nine groin and six retroperitoneal hematomas ) ( 0.06 % ) , and 4 arterial dissections ( 0.02 % ) . Risk factors for complications were left sided femoral access ( OR 4.11 [ 2.29 - 7.37 ] p<0.001 ) , peripheral arterial disease ( PAD ) ( OR 2.42 [ 1.48 - 3.94 ] p<0.0001 ) and female sex ( OR 2.22 [ 1.51 - 3.24 ] p<0.0001 ) . CONCLUSION Vascular complications related to femoral access in coronary diagnostic and interventional procedures are low ( 0.54 % ) . Risk factors were left sided access , PAD , and female sex OBJECTIVE Cognitive remediation ( CR ) approaches have demonstrated to be effective in improving cognitive functions in schizophrenia . However , there is a lack of integrated CR approaches that target multiple neuro- and social-cognitive domains with a special focus on the generalization of therapy effects to functional outcome . METHOD This 8-site r and omized controlled trial evaluated the efficacy of a novel CR group therapy approach called integrated neurocognitive therapy ( INT ) . INT includes well-defined exercises to improve all neuro- and social-cognitive domains as defined by the Measurement And Treatment Research to Improve Cognition in Schizophrenia ( MATRICS ) initiative by compensation and restitution . One hundred and fifty-six out patients with a diagnosis of schizophrenia or schizoaffective disorder according to DSM-IV-TR or ICD-10 were r and omly assigned to receive 15 weeks of INT or treatment as usual ( TAU ) . INT patients received 30 bi-weekly therapy sessions . Each session lasted 90min . Mixed models were applied to assess changes in neurocognition , social cognition , symptoms , and functional outcome at post-treatment and at 9-month follow-up . RESULTS In comparison to TAU , INT patients showed significant improvements in several neuro- and social-cognitive domains , negative symptoms , and functional outcome after therapy and at 9-month follow-up . Number-needed-to-treat analyses indicate that only 5 INT patients are necessary to produce durable and meaningful improvements in functional outcome . CONCLUSIONS Integrated interventions on neurocognition and social cognition have the potential to improve not only cognitive performance but also functional outcome . These findings are important as treatment guidelines for schizophrenia have criticized CR for its poor generalization effects BACKGROUND The use of transcatheter mitral valve repair ( TMVR ) has gained widespread acceptance in Europe , but data on immediate success , safety , and long-term echocardiographic follow-up in real-world patients are still limited . OBJECTIVES The aim of this multinational registry is to present a real-world overview of TMVR use in Europe . METHODS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospect i ve , independent , consecutive collection of individual patient data . RESULTS A total of 628 patients ( mean age 74.2 ± 9.7 years , 63.1 % men ) underwent TMVR between January 2011 and December 2012 in 25 centers in 8 European countries . The prevalent pathogenesis was functional mitral regurgitation ( FMR ) ( n = 452 [ 72.0 % ] ) . The majority of patients ( 85.5 % ) were highly symptomatic ( New York Heart Association functional class III or higher ) , with a high logistic EuroSCORE ( European System for Cardiac Operative Risk Evaluation ) ( 20.4 ± 16.7 % ) . Acute procedural success was high ( 95.4 % ) and similar in FMR and degenerative mitral regurgitation ( p = 0.662 ) . One clip was implanted in 61.4 % of patients . In-hospital mortality was low ( 2.9 % ) , without significant differences between groups . The estimated 1-year mortality was 15.3 % , which was similar for FMR and degenerative mitral regurgitation . The estimated 1-year rate of rehospitalization because of heart failure was 22.8 % , significantly higher in the FMR group ( 25.8 % vs. 12.0 % , p[log-rank ] = 0.009 ) . Paired echocardiographic data from the 1-year follow-up , available for 368 consecutive patients in 15 centers , showed a persistent reduction in the degree of mitral regurgitation at 1 year ( 6.0 % of patients with severe mitral regurgitation ) . CONCLUSIONS This independent , contemporary registry shows that TMVR is associated with high immediate success , low complication rates , and sustained 1-year reduction of the severity of mitral regurgitation and improvement of clinical symptoms OBJECTIVE To assess patients with SSc who present without circulating ANAs or RP . METHODS Five thous and three hundred and ninety patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials and Research ( EUSTAR ) data base were screened for the absence of both RP and circulating ANA . To differentiate SSc from its mimics , additional information was gathered using a st and ardized question naire . RESULTS Five thous and three hundred and seventy-eight ( 99.8 % ) of the 5390 SSc patients in the EUSTAR data base had either detectable ANA or a history of RP . Twelve ( 0.2 % ) patients lacked both circulating ANA and RP . Details of the medical history could be obtained for seven patients . Three cases were compatible with ANA-negative and RP-negative SSc and were not typical of any known SSc mimic . Four patients had a malignancy : two had breast cancer , one had multiple myeloma with possible scleromyxoedema and one had bladder carcinoma . There was no temporal relationship between the onset of skin fibrosis and that of the tumour . Although no patient with confirmed nephrogenic systemic fibrosis was identified among the cases of ANA-negative and RP-negative SSc , the presentation of one patient could be compatible with that of nephrogenic systemic fibrosis other than for the absence of chronic kidney disease or of known prior gadolinium exposure . CONCLUSION We have identified a very small subgroup of SSc patients who lack both circulating ANA and RP , none of whom fulfils the diagnostic criteria for any known SSc mimic . Prospect i ve studies are needed to eluci date the clinical presentation , evolution and outcome of such patients We compared implementation of systematic airway assessment with existing practice of airway assessment on prediction of difficult mask ventilation . Twenty‐six departments were cluster‐r and omised to assess eleven risk factors for difficult airway management ( intervention ) or to continue with their existing airway assessment ( control ) . In both groups , patients predicted as a difficult mask ventilation and /or difficult intubation were registered in the Danish Anaesthesia Data base , with a notational summary of airway management . The trial 's primary outcome was the respective incidence of unpredicted difficult and easy mask ventilation in the two groups . Among 94,006 patients undergoing mask ventilation , the incidence of unpredicted difficult mask ventilation in the intervention group was 0.91 % and 0.88 % in the control group ; ( OR ) 0.98 ( 95 % CI 0.66–1.44 ) , p = 0.90 . The incidence of patients predicted difficult to mask ventilate , but in fact found to be easy ( ‘ falsely predicted difficult ’ ) was 0.64 % vs. 0.35 % ( intervention vs. control ) ; OR 1.56 ( 1.01–2.42 ) , p = 0.045 . In the intervention group , 86.3 % of all difficult mask ventilations were not predicted , compared with a higher proportion 91.2 % in the control group , OR 0.61 ( 0.41–0.91 ) , p = 0.016 . The systematic intervention did not alter the overall incidence of unpredicted difficult mask ventilations , but of the patients who were found to be difficult to mask ventilate , the proportion predicted was higher in the intervention group than in the control group . However , this was at a ‘ cost ’ of increasing the number of mask ventilations falsely predicted to be difficult OBJECTIVE The purpose s of this study were to measure the prevalence of clinical and radiographic hip osteoarthritis ( OA ) and first-time diagnosis of hip OA in consecutive patients presenting to chiropractic practice s in Denmark and to report the components of the initial treatment rendered by the chiropractic practitioner . METHODS A total of 2000 patient records and 1000 radiographs were review ed retrospectively in 20 chiropractic clinics throughout Denmark . Information obtained included patients ' primary complaint , physical examination and radiographic findings of hip OA , and treatment . Subsequently , the 20 clinics participated in a prospect i ve survey where they collected equivalent information over a 2-week period . RESULTS Retrospective review of records revealed that 1.4 % of patients in Danish chiropractic practice had signs of clinical hip OA . Of these , 59 % demonstrated radiographic signs of hip OA . Prospect i ve data collection revealed that 3.4 % of new patients had signs of clinical hip OA . Fifty-four percent of these demonstrated radiographic signs of hip OA , and of these 70 % were diagnosed as having OA of the hip for the first time . Initial treatment involved manual treatment and advice on over-the-counter pain medication and /or supplements . Of all 1000 retrospectively review ed radiographs in patients 40 years or older , 19.2 % demonstrated radiographic signs of hip OA . CONCLUSION Osteoarthritis of the hip is diagnosed and managed in primary care chiropractic practice in Denmark ; however , it is likely underdiagnosed . In those newly presenting to chiropractic practitioners , first-time diagnosis with clinical and radiographic signs of hip OA appears to be common Objectives We compared the effectiveness of the Gold St and ard Programme ( a comprehensive smoking cessation intervention commonly used in Denmark ) with other face-to-face smoking cessation programmes in Denmark after implementation in real life , and we identified factors associated with successful quitting . Design Prospect i ve cohort study . Setting A total of 423 smoking cessation clinics from different setting s reported data from 2001 to 2013 . Participants In total , 82 515 patients were registered . Smokers ≥15 years old and attending a programme with planned follow-up were included . Smokers who did not want further contact , who intentionally were not followed up or who lacked information about the intervention they received were excluded . A total of 46 287 smokers were included . Interventions Various real-life smoking cessation interventions were identified and compared : The Gold St and ard Programme , Come & Quit , crash courses , health promotion counselling ( brief intervention ) and other interventions . Main outcome Self-reported continuous abstinence for 6 months . Results Overall , 33 % ( 11 184 ) were continuously abstinent after 6 months ; this value was 24 % when non-respondents were considered smokers . The follow-up rate was 74 % . Women were less likely to remain abstinent , OR 0.83 ( CI 0.79 to 0.87 ) . Short interventions were more effective among men . After adjusting for confounders , the Gold St and ard Programme was the only intervention with significant results across sex , increasing the odds of abstinence by 69 % for men and 31 % for women . In particular , compliance , and to a lesser degree , mild smoking , older age and not being disadvantaged were associated with positive outcomes for both sexes . Compliance increased the odds of abstinence more than 3.5-fold . Conclusions Over time , Danish smoking cessation interventions have been effective in real life . Compliance is the main predictor of successful quitting . Interestingly , short programmes seem to have relatively strong effects among men , but the absolute numbers are very small . Only the comprehensive Gold St and ard Programme works across sexes Objectives To estimate the occurrence of and risk factors associated with genital warts in Danish men Methods We conducted a cross-sectional , question naire-based study among almost 23 000 men aged 18–45 years , r and omly sample d from the general population of Denmark . Data was collected on self-reported clinical ly diagnosed genital warts , and various lifestyle habits . Results Ever having had clinical ly diagnosed genital warts was reported by 7.9 % of the men . The median age at first occurrence was 22 years . Genital warts within the previous 12 months were reported by 0.92 % of the men , with a peak of 1.83 % among men aged 21–24 years . The likelihood of reporting genital warts was strongly correlated with the lifetime number of sex partners ( OR 8.0 ; 95 % CI 6.0 to 10.8 for ≥15 partners vs 1–2 partners ) . Other factors associated with an increased risk for genital warts included ever having smoked and having had other sexually transmitted infections . Conclusions Almost 8 % of Danish men aged 18–45 years reported having had a diagnosis of genital warts . The results provide baseline information for developing and monitoring prevention strategies against genital warts , such as vaccination against human papillomavirus types 6 and 11 Abstract Purpose : One established risk factors for testicular cancer is cryptorchidism . However , it remains unclear whether cryptorchidism is a risk factor in itself or whether the two conditions share common causes in early life ( estrogen hypothesis ) , such as birth weight and birth order . The objective of this study is to utilize data from the Copenhagen School Health Records Register ( CSHRR ) to evaluate cryptorchidism , birth weight and birth order as risk factors for testicular cancer . Methods : The study population consisted of 408 cases of testicular cancer identified by a government issued identification number linkage of the entire CSHRR with the Danish Cancer Registry and a r and om sub sample of 4819 males from the CSHRR . The study design was case-cohort and the period of follow-up between 2 April 1968 and 31 December 2003 . Results : Cryptorchidism was significantly associated with testicular cancer in crude analyses [ hazard ratio ( HR ) = 3.60 , 95 % CI 2.79–4.65 ] . Birth weight was inversely associated with testicular cancer and no clear association with birth order was observed . The positive association between cryptorchidism and testicular cancer was only slightly attenuated controlling for birth weight and birth order and stratified on birth cohort ( HR = 3.46 , 95 % CI 2.67–4.48 ) . Conclusion : This study confirmed the robustness of the association between cryptorchidism and testicular cancer even after adjustment for birth weight and birth order . Furthermore , the study showed an inverse association between birth weight and testicular cancer Purpose The purpose of MOthers and BAbies in Norway and Denmark cerebral palsy ( MOB AND -CP ) was to study CP aetiology in a prospect i ve design . Participants MOB AND -CP is a cohort of more than 210 000 children , created as a collaboration between the world 's two largest pregnancy cohorts — the Norwegian Mother and Child Cohort study ( MoBa ) and the Danish National Birth Cohort . MOB AND -CP includes maternal interview/ question naire data collected during pregnancy and follow-up , plus linked information from national health registries . Findings to date Initial harmonisation of data from the 2 cohorts has created 140 variables for children and their mothers . In the MOB AND -CP cohort , 438 children with CP have been identified through record linkage with vali date d national registries , providing by far the largest such sample with prospect ively collected detailed pregnancy data . Several studies investigating various hypotheses regarding CP aetiology are currently on-going . Future plans Additional data can be harmonised as necessary to meet requirements of new projects . Biological specimens collected during pregnancy and at delivery are potentially available for assay , as are results from assays conducted on these specimens for other projects . The study size allows consideration of CP subtypes , which is rare in aetiological studies of CP . In addition , MOB AND -CP provides a platform within the context of a merged birth cohort of exceptional size that could , after appropriate permissions have been sought , be used for cohort and case-cohort studies of other relatively rare health conditions of infants and children BACKGROUND We hypothesized that undergoing surgery as soon as possible reduces early mortality in patients with a proximal femoral fracture . Our aim was to evaluate the association between surgical delay and early mortality in these patients . METHODS We performed a retrospective analysis of prospect ively collected data from the Danish Fracture Data base and the Civil Registration System on patients who were fifty years of age or older and had undergone surgery for a proximal femoral fracture . Femoral head fracture ( classified as OTA/AO 31C per the OTA/AO classification system ) , high-energy trauma , pathological fractures , multiple fractures , and surgeries performed with implants not commonly used were excluded . End points were adjusted odds ratios for thirty-day and ninety-day mortality . RESULTS For the 3517 surgeries included in this study , the median patient age was 82.0 years ( range , fifty-one to 107 years ) , 2458 patients ( 70 % ) were female , and 1720 surgeries ( 49 % ) were performed because of a trochanteric fracture . Within twelve hours , 722 of the surgeries ( 21 % ) had been performed ; within twenty-four hours , 2482 surgeries ( 71 % ) ; within thirty-six hours , 3024 surgeries ( 86 % ) ; within forty-eight hours , 3242 surgeries ( 92 % ) ; and within seventy-two hours , 3353 surgeries ( 95 % ) . Unsupervised surgeons with an education level below that of an attending surgeon performed the surgery in 1807 ( 51 % ) of all cases . The thirty-day mortality was 380 ( 10.8 % ) and the ninety-day mortality was 612 ( 17.4 % ) . The risk of thirty-day mortality increased with a surgical delay of more than twelve hours ( odds ratio , 1.45 ; p = 0.02 ) , more than twenty-four hours ( odds ratio , 1.34 ; p = 0.02 ) , and more than forty-eight hours ( odds ratio , 1.56 ; p = 0.02 ) ; the risk of ninety-day mortality increased with a surgical delay of more than twenty-four hours ( odds ratio , 1.23 ; p = 0.04 ) . An education level of the surgeon below that of an attending surgeon increased the risk of thirty-day mortality ( odds ratio , 1.28 ; p = 0.035 ) and ninety-day mortality ( odds ratio , 1.26 ; p = 0.016 ) . Increasing American Society of Anesthesiologists score and male sex significantly increased both thirty-day and ninety-day mortality . CONCLUSIONS In this study , a surgical delay of more than twelve hours significantly increased the adjusted risk of thirty-day mortality and a surgical delay of more than twenty-four hours significantly increased the adjusted risk of ninety-day mortality . The adjusted risk of both thirty-day and ninety-day mortality increased significantly when the education level of the surgeon was below that of an attending surgeon . The study findings challenge orthopaedic departments to facilitate fast surgical treatment supported by attending orthopaedic surgeons Summary Background Prospect i ve systematic analyses of the clinical presentation of bullous pemphigoid ( BP ) are lacking . Little is known about the time required for its diagnosis . Knowledge of the disease spectrum is important for diagnosis , management and inclusion of patients in therapeutic trials BACKGROUND Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation ( APBI ) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival . Here , we present 5-year results of patient-reported quality of life . METHODS We did this r and omised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries . Patients aged 40 years or older with 0-IIA breast cancer were r and omly assigned ( 1:1 ) after breast-conserving surgery ( resection margins ≥2 mm ) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy . R and omisation was stratified by study centre , tumour type , and menopausal status , with a block size of ten and an automated dynamic algorithm . There was no masking of patients or investigators . The primary endpoint of the trial was ipsilateral local recurrence . Here , we present 5-year results of quality of life ( a prespecified secondary endpoint ) . Quality -of-life question naires ( European Organisation for Research and Treatment of Cancer QLQ-C30 , breast cancer module QLQ-BR23 ) were completed before radiotherapy ( baseline 1 ) , immediately after radiotherapy ( baseline 2 ) , and during follow-up . We analysed the data according to treatment received ( as-treated population ) . Recruitment was completed in 2009 , and long-term follow-up is continuing . The trial is registered at Clinical Trials.gov , number NCT00402519 . FINDINGS Between April 20 , 2004 , and July 30 , 2009 , 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation . Quality -of-life question naires at baseline 1 were available for 334 ( 53 % ) of 663 patients in the APBI group and 314 ( 57 % ) of 551 patients in the whole-breast irradiation group ; the response rate was similar during follow-up . Global health status ( range 0 - 100 ) was stable in both groups : at baseline 1 , APBI group mean score 65·5 ( SD 20·6 ) versus whole-breast irradiation group 64·6 ( 19·6 ) , p=0·37 ; at 5 years , APBI group 66·2 ( 22·2 ) versus whole-breast irradiation group 66·0 ( 21·8 ) , p=0·94 . The only moderate , significant difference ( difference of 10 - 20 points ) between the groups was found in the breast symptoms scale . Breast symptom scores were significantly higher ( ie , worse ) after whole-breast irradiation than after APBI at baseline 2 ( difference of means 13·6 , 95 % CI 9·7 - 17·5 ; p<0·0001 ) and at 3-month follow-up ( difference of means 12·7 , 95 % CI 9·8 - 15·6 ; p<0·0001 ) . INTERPRETATION APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation . This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer . FUNDING German Cancer Aid STUDY QUESTION Do fertility drugs increase the risk for borderline ovarian tumours , overall and according to histological subtype ? SUMMARY ANSWER The use of any fertility drug did not increase the overall risk for borderline ovarian tumours , but an increased risk for serous borderline ovarian tumours was observed after the use of progesterone . WHAT IS KNOWN ALREADY Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer ; most have found no strong association . Fewer studies have assessed the association between use of fertility drugs and risk for borderline ovarian tumours , and the results are inconsistent . STUDY DESIGN , SIZE , DURATION A retrospective case-cohort study was design ed with data from a cohort of 96 545 Danish women with fertility problems referred to all Danish fertility clinics in the period 1963 - 2006 . All women were followed for first occurrence of a borderline ovarian tumour from the initial date of infertility evaluation until a date of migration , date of death or 31 December 2006 , whichever occurred first . The median length of follow-up was 11.3 years . PARTICIPANTS / MATERIAL S , SETTING , METHODS Included in the analyses were 142 women with borderline ovarian tumours ( cases ) and 1328 r and omly selected sub-cohort members identified in the cohort during the follow-up through 2006 . Cases were identified by linkage to the Danish Cancer Register and the Danish Register of Pathology by use of personal identification numbers . To obtain information on use of fertility drugs , hospital files and medical records of infertility-associated visits to all Danish fertility clinics were collected and supplemented with information from the Danish IVF register . We used case-cohort techniques to calculate rate ratios ( RRs ) and corresponding 95 % confidence intervals ( CIs ) for borderline ovarian tumours , overall and according to histological subtype , associated with the use of any fertility drug or five specific groups of fertility drugs : clomiphene citrate , gonadotrophins ( human menopausal gonadotrophins and follicle-stimulating hormone ) , gonadotrophin-releasing hormone analogues , human chorionic gonadotrophins and progesterone . MAIN RESULTS AND THE ROLE OF CHANCE Analyses within the cohort showed that the overall risk for borderline ovarian tumours was not associated with the use of any fertility drug ( RR 1.00 ; 95 % CI 0.67 - 1.51 ) or of gonadotrophins ( RR 1.32 ; 95 % CI 0.81 - 2.14 ) , clomiphene citrate ( RR 0.96 ; 95 % CI 0.64 - 1.44 ) , human chorionic gonadotrophins ( RR 0.91 ; 95 % CI 0.61 - 1.36 ) or gonadotrophin-releasing hormone analogues ( RR 1.10 ; 95 % CI 0.66 - 1.81 ) . Furthermore , no associations were observed between the risk for borderline ovarian tumours and these groups of fertility drugs according to the number of cycles of use , length of follow-up or parity . In contrast , use of progesterone increased the risk for borderline ovarian tumours , particularly serous tumours , for which statistically significantly increased risks were observed with any use of progesterone ( RR 1.82 ; 95 % CI 1.03 - 3.24 ) , among women treated with ≥4 cycles of progesterone ( RR 2.63 ; 95 % CI 1.04 - 6.64 ) and for all women followed up for ≥4 years after their first treatment with progesterone . LIMITATIONS , REASONS FOR CAUTION Although we tried to minimize the effects of the underlying infertility , the severity of infertility might have affected our risk estimates , as women with more severe fertility problems may receive more treatment . The results from the subgroup analyses , e.g. the findings of an elevated risk for borderline ovarian tumours associated with increased time since first use of progesterone and with increased number of treatment cycles , should be interpreted with caution as these analyses are based on a limited number of women with borderline ovarian tumours . WIDER IMPLICATION S OF THE FINDINGS Although this study , which is the largest to date , provides reassuring evidence that there is no strong link between the use of fertility drugs and risk for borderline ovarian tumours , the novel observation of an increased risk for serous tumours after use of progesterone should be investigated in large epidemiological studies . The results of the present study provide valuable knowledge for clinicians and other health care personnel involved in the diagnosis and treatment of fertility problems . STUDY FUNDING /COMPETING INTERESTS No conflict of interest was reported . S.M.B. was supported by a research scholarship from the Danish Cancer Society Background In 2010 the ‘ Polymedication Check ’ ( PMC ) , a pharmacist-led medication review , was newly introduced to be delivered independently from the prescriber and reimbursed by the Swiss health insurances . This study aim ed at evaluating the impact of this new cognitive service focusing on medicines use and patients ’ adherence in everyday life . Methods This r and omised controlled trial was conducted in 54 Swiss community pharmacies . Eligible patients used ≥4 prescribed medicines over > 3 months . The intervention group received a PMC at study start ( T-0 ) and after 28 weeks ( T-28 ) while the control group received only a PMC at T-28 . Primary outcome measure was change in patients ’ objective adherence , calculated as Medication Possession Ratio ( MPR ) and Daily Polypharmacy Possession Ratio ( DPPR ) , using refill data from the pharmacies and patient information of dosing . Subjective adherence was assessed as secondary outcome by self-report question naires ( at T-0 and T-28 ) and telephone interviews ( at T-2 and T-16 ) , where participants estimated their overall adherence on a scale from 0–100 % . Results and discussion A total of 450 patients were r and omly allocated to intervention ( N = 218 , 48.4 % ) and control group ( N = 232 , 51.6 % ) . Dropout rate was fairly low and comparable for both groups ( NInt = 37 ( 17.0 % ) , NCont = 41 ( 17.7 % ) , p = 0.845 ) . Main addressed drug-related problem ( DRP ) during PMC at T-0 was insufficient adherence to at least one medicine ( N = 69 , 26.7 % ) . At T-28 , 1020 chronic therapies fulfilled inclusion criteria for MPR calculation , representing 293 of 372 patients ( 78.8 % ) . Mean MPR and adherence to polypharmacy ( DPPR ) for both groups were equally high ( MPRInt = 88.3 , SD = 19.03 ; MPRCont = 87.5 , SD = 20.75 ( p = 0.811 ) and DPPRInt = 88.0 , SD = 13.31 ; DPPRCont = 87.5 , SD = 20.75 ( p = 0.906 ) , respectively).Mean absolute change of subjective adherence between T-0 and T-2 was + 1.03 % in the intervention and −0.41 % in the control group ( p = 0.058 ) . The number of patients reporting a change of their adherence of more than ±5 points on a scale 0–100 % between T-0 and T-2 was significantly higher in the intervention group ( NImprovement = 30 ; NWorsening = 14 ) than in the control group ( NImprovement = 20 ; NWorsening = 24 ; p = 0.028 ) . Conclusion Through the PMC pharmacist were able to identify a significant number of DRPs . Participants showed high baseline objective adherence of 87.5 % , providing little potential for improvement . Hence , no significant increase of objective adherence was observed . However , regarding changes in subjective adherence of more than ±5 % the PMC showed a positive effect . Trial registration Clinical trial registry data base , NCT01739816 ; first entry on November 27 , 2012 Exact cause and manner of death determination improves legislative safety for the individual and for society and guides aspects of national public health . In the International Classification of Diseases , codes R00-R99 are used for " symptoms , signs and abnormal clinical and laboratory findings , not elsewhere classified " design ated as " ill-defined " or " with unknown etiology " . The World Health Organisation recommends avoiding the use of ill-defined and unknown causes of death in the death certificate as this terminology does not give any information concerning the possible conditions that led to the death . Thus , the aim of the study was , firstly , to analyse the frequencies of R00-R99-coded deaths in mortality statistics in Finl and and in Denmark and , secondly , to compare these and the methods used to investigate the cause of death . To do so , we extracted a r and om 90 % sample of the Finnish death certificates and 100 % of the Danish certificates from the national mortality registries for 2000 , 2005 and 2010 . Subsequently , we analysed the frequencies of forensic and medical autopsies and external clinical examinations of the bodies in R00-R99-coded deaths . The use of R00-R99 codes was significantly higher in Denmark than in Finl and ; OR 18.6 ( 95 % CI 15.3 - 22.4 ; p<0.001 ) for 2000 , OR 9.5 ( 95 % CI 8.0 - 11.3 ; p<0.001 ) for 2005 and OR 13.2 ( 95 % CI 11.1 - 15.7 ; p<0.001 ) for 2010 . More than 80 % of Danish deaths with R00-R99 codes were over 70 years of age at the time of death . Forensic autopsy was performed in 88.3 % of Finnish R00-R99-coded deaths , whereas only 3.5 % of Danish R00-R99-coded deaths were investigated with forensic or medical autopsy . The codes that were most used in both countries were R96-R99 , meaning " unknown cause of death " . In Finl and , all of these deaths were investigated with a forensic autopsy . Our study suggests that if all deaths in all age groups with unclear cause of death were systematic ally investigated with a forensic autopsy , only 2 - 3/1000 deaths per year would be coded as an ill-defined and unknown cause of death in national mortality statistics . At the same time the risk to overlook unnatural deaths is decreased to a minimum . To achieve this in Denmark requires that the existing legislation on cause of death investigation would need to be changed to ensure that all deaths with unknown cause of death are investigated with a forensic autopsy Background R and omized controlled trials have demonstrated that a restrictive red blood cell ( RBC ) transfusion strategy lowers transfusion frequency without affecting mortality . However , the external validity of these trials has not been tested in a large cohort . The purpose was to estimate the effect of introducing a National Clinical Guideline ( NCG ) for a restrictive hemoglobin transfusion threshold on transfusion frequency and mortality in hip fracture patients > 65 years old . Methods A consecutive cohort study of hip fracture patients > 65 years old residing in the southern region of Denmark was conducted using prospect ively gathered data from registers during two separate 1-year time periods . The first period from October 1 , 2012 , to September 30 , 2013 , included 1494 patients and used a liberal transfusion threshold , whereas the second period from October 1 , 2015 , to September 30 , 2016 , including 1414 participants used a restrictive threshold from the NCG . Participant data for age , sex , body mass index , Charlson Comorbidity Index , time to surgery , and death were retrieved from the Danish Interdisciplinary Registry of Hip Fractures and were merged with RBC transfusion and medication data extracted from the Danish Transfusion and Odense Pharmacoepidemiological Data bases , respectively . Cox proportional hazards models were used to test relative mortality risk for the restrictive group compared with the liberal group at 30 and 90 days . Results Overall RBC transfusions decreased from 42 to 30 % ( p < 0.001 ) . The 30-day mortality rate ( 95 % CI ) was 9 % ( 8;11 ) in the restrictive group and 13 % ( 11;14 ) in the liberal group ( p < 0.008 ) , whereas the adjusted relative mortality risk was 0.72 ( 0.57;0.91 ) . The 90-day mortality rate was 15 % ( 13;17 ) in the restrictive group and 19 % ( 17;21 ) in the liberal group , whereas the adjusted relative mortality risk was 0.78 ( 0.65;0.94 ) . Conclusion These data suggest that the introduction of an NCG on restrictive blood transfusion leads to lower transfusion frequency in hip fracture patients > 65 years old . Even though this reduction is associated with decreased mortality at both 30 and 90 days , it may be explained by other issues than restrictive transfusion strategy . There has been an improvement in the mortality of hip fracture patients in Denmark , and we suggest that a restrictive transfusion strategy does not lead to increased mortality Background and Purpose — R and omized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery . We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists ’ Collaboration data base . Methods — The Carotid Stenting Trialists ’ Collaboration is a pooled individual patient data base including all patients recruited in 3 r and omized trials of stenting versus endarterectomy for symptomatic carotid stenosis ( Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial , Stent-Protected Angioplasty versus Carotid Endarterectomy trial , and International Carotid Stenting Study ) . Lifetime carotid artery stenting experience , lifetime experience in stenting procedures excluding the carotid , and annual number of procedures performed within the trial ( in-trial volume ) , divided into tertiles , were used to measure operator experience . The outcome event was the occurrence of any stroke or death within 30 days of the procedure . The analysis was done per protocol . Results — Among 1546 patients who underwent carotid artery stenting , 120 ( 7.8 % ) had a stroke or death within 30 days of the procedure . The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience ( P=0.8 ) or operator lifetime stenting experience excluding the carotid ( P=0.7 ) . In contrast , the 30-day risk of stroke or death was significantly higher in patients treated by operators with low ( mean ⩽3.2 procedures /y ; risk 10.1 % ; adjusted risk ratio=2.30 [ 1.36–3.87 ] ) and intermediate annual in-trial volumes ( 3.2–5.6 procedures /y ; 8.4 % ; adjusted risk ratio=1.93 [ 1.14–3.27 ] ) compared with patients treated by high annual in-trial volume operators ( > 5.6 procedures /y ; 5.1 % ) . Conclusions — Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year Background : R and omised studies suggest regional anaesthesia to have the highest morbidity and local infiltration anaesthesia to have the lowest morbidity after groin hernia repair . However , implication s and results of this evidence for general practice are not known Abstract Background Conventional laparoscopic cholecystectomy ( CLC ) is regarded as the gold st and ard for cholecystectomy . However , single-incision laparoscopic cholecystectomy ( SLC ) has been suggested to replace CLC . This study aim ed at comparing long-term incidences of port-site hernia and chronic pain after SLC versus CLC . Methods We conducted a matched cohort study based on prospect i ve data ( Jan 1 , 2009–June 1 , 2011 ) from the Danish Cholecystectomy Data base with perioperative information and clinical follow-up . Consecutive patients undergoing elective SLC during the study period were included and matched 1:2 with patients subjected to CLC using pre-defined criteria . Follow-up data were obtained from the Danish National Patient Registry , mailed patient question naires , and clinical examination . A port-site hernia was defined as a repair for a port-site hernia or clinical hernia located at one or more port sites . Results In total , 699 patients were eligible and 147 patients were excluded from the analysis due to pre-defined criteria . The rate of returned question naires was 83 % . Thus , 552 ( SLC , n = 185 ; CLC , n = 367 ) patients were analyzed . The median observation time was 48 months ( range 1–65 ) after SLC and 48 months ( 1–64 ) after CLC ( P = 0.940 ) . The total cumulated port-site hernia rate was 4 % and 6 % for SLC and CLC , respectively ( P = 0.560 ) . Incidences of moderate/severe chronic pain were 4 % and 5 % after SLC and CLC , respectively ( P = 0.661 ) . Conclusions We found no difference in long-term incidence of port-site hernia or chronic pain after SLC versus CLC Objective . Surgical‐site infections are serious complications and thorough follow‐up is important for accurate surveillance . We aim ed to compare the frequency of complications recorded in a clinical quality data base with those noted in a r and omized clinical trial with follow‐up visits . Design . Evaluation study . Setting . Danish Gynecological Cancer Data base ( DGCD ) and the Danish multicenter trial on perioperative oxygen and surgical‐site infections ( PROXI ) . Sample . Paired data from 222 patients who participated in the PROXI trial taking place at Copenhagen University Hospital , Rigshospitalet between November 2006 and October 2008 and data from the DGCD . Methods . Outcomes within 30 days from the trial and the data base were compared and levels of agreements were calculated with kappa‐statistics . Main Outcome Measures . Primary outcome was surgical‐site infection . Other outcomes included re‐operation , urinary tract infection , pneumonia and sepsis . Results . Surgical‐site infection was found in 21 of 222 patients ( 9.5 % ) in the PROXI trial versus 6 of 222 patients ( 2.7 % ) in the DGCD ( p < 0.01 , kappa 0.42 ) . Twelve of 15 superficial and three of six deep or organ‐space surgical‐site infections were registered in the PROXI trial , but not in the DGCD . Agreements between secondary outcomes were very varying ( kappa‐value 0.77 for re‐operation , 0.37 for urinary tract infections , 0.19 for sepsis and 0.18 for pneumonia ) . Conclusions . The r and omized trial reported significantly more surgical‐site infections than the clinical data base . The DGCD reported only 50 % of the deep and organ‐space infections , and hence , the low‐overall agreement indicates a need for more careful data base registration BACKGROUND AND AIMS High sodium ( Na ) and low potassium ( K ) intake are associated with hypertension and CVD risk . This study explored the associations of health literacy ( HL ) , food literacy ( FL ) , and salt awareness with salt intake , K intake , and Na/K ratio in a workplace intervention trial in Switzerl and . METHODS AND RESULTS The study acquired baseline data from 141 individuals , mean age 44.6 years . Na and K intake were estimated from a single 24-h urine collection . We applied vali date d instruments to assess HL and FL , and salt awareness . Multiple linear regression was used to investigate the association of explanatory variables with salt intake , K intake , and Na/K. Mean daily salt intake was 8.9 g , K 3.1 g , and Na/K 1.18 . Salt intake was associated with sex ( p < 0.001 ) , and K intake with sex ( p < 0.001 ) , age ( p = 0.02 ) , and waist-to-height ratio ( p = 0.03 ) , as was Na/K. HL index and FL score were not significantly associated with salt or K intake but the awareness variable " salt content impacts food/menu choice " was associated with salt intake ( p = 0.005 ) . CONCLUSION To achieve the established targets for population Na and K intake , health-related knowledge , abilities , and skills related to Na/salt and K intake need to be promoted through combined educational and structural interventions . Clinical Trials Registry number : DRKS00006790 ( 23/09/2014 ) OBJECTIVES Despite a broad and efficient pharmacological antihypertensive armamentarium , blood pressure ( BP ) control is suboptimal and heterogeneous throughout Europe . Recent representative data from Switzerl and are limited . The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerl and in accordance with current guidelines . The influence of risk factors , target organ damage and medication on BP levels and control was also evaluated . METHODS A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerl and . 281 r and omly selected physicians provided data on 5 consecutive hypertensive patients attending their practice s for BP follow-up . Data were anonymously collected on demographics , comorbidities and current medication , and BP was recorded . Subsequent modification of pharmacological antihypertensive therapy was assessed . RESULTS Data from 1376 patients were available . Mean age was 65 ± 12 years , 53.9 % were male subjects . 26.4 % had complicated hypertension . Overall , BP control ( < 140/90 mm Hg for uncomplicated and < 130/80 mm Hg for complicated hypertension ) was achieved in 48.9 % . Compared to patients with complicated hypertension , BP control was better in patients with uncomplicated hypertension ( 59.4 % vs. 19.2 % , p < 0.001 ) . As a monotherapy the most prescribed drug class were angiotensin receptor blockers ( ARB , 41 % ) , followed by angiotensin converting enzyme ( ACE ) inhibitors ( 21.5 % ) , betablockers ( 20.8 % ) and calcium channel blockers ( CCB , 10.8 % ) . The most prescribed drug combinations were ARB + diuretic ( 30.1 % ) and ACE inhibitors + diuretic ( 15.3 % ) . 46 % were receiving a fixed drug combination . In only 32.7 % of patients with uncontrolled hypertension was a change in drug therapy made . CONCLUSION This representative survey on treated adult hypertensive patients shows that , compared to earlier reports , the control rate of hypertension has improved in Switzerl and for uncomplicated but not for complicated , particularly diabetes-associated hypertension . ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy , whereas diuretics and ARBs were the most used for combination therapy Introduction . Since 30 years , DBCG ( Danish Breast Cancer Cooperative Group ) has maintained a clinical data base allowing the conduct of quality control studies , of r and omised trials , examination of the epidemiology of breast cancer and of prognostic and predictive factors . Material and methods . The original data base included patients with invasive breast cancer , but has later been exp and ed to patients with in situ breast cancer and hereditary breast and ovarian cancer families . Results . The multidisciplinary cooperative group has provided successive treatment guidelines and 70 % of the 77284 registered patients have been enrolled and received treatment according to these guidelines . The st and ard treatments and the r and omised trials included in the DBCG programmes are all briefly described . Among high-risk patients 48 % have participated in r and omised trials , and the results of these trials have largely been implemented in the next generation of treatment guidelines . Records within the clinical data base of archival tumour tissue have established a basis for translational research and epidemiologic research has been enabled through linkage to other healthcare registries . Discussion . The joint conception of the multidisciplinary breast cancer group and a clinical data base has provided improvements in the management of breast cancer patients and has enabled recruitment of patients onto r and omised trials Objective . The role of analgesic drug use in development of ovarian cancer is not fully understood . We examined the association between analgesic use and risk of ovarian cancer . In addition , we examined whether the association differed according to histological types . Design . Population ‐based case – control study . Setting . Denmark in the period 1995–1999 . Population . We included 756 women with epithelial ovarian cancer and 1564 r and omly selected control women aged 35–79 years . Methods . Information on analgesic drug use was collected from personal interviews . Analgesic drugs were divided into the following categories : any analgesics ; aspirin ; non‐aspirin non‐steroidal anti‐inflammatory drugs ; paracetamol ; and other analgesic drugs . The association between analgesic drug use and ovarian cancer risk was analysed using multiple logistic regression models . Odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) were estimated . Main outcome measures . Epithelial ovarian cancer . Results . Women with a regular use of any analgesics ( OR = 0.79 ; 95 % CI 0.62 − 1.01 ) or aspirin ( OR = 0.68 ; 95 % CI 0.46 − 1.02 ) had a decreased risk of ovarian cancer , although not statistically significant . Regular use of non‐aspirin non‐steroidal anti‐inflammatory drugs , paracetamol or other analgesics did not decrease ovarian cancer risk . Use of any analgesics ( OR = 0.72 ; 95 % CI 0.53–0.98 ) or aspirin ( OR = 0.60 ; 95 % CI 0.36–1.00 ) result ed in a statistically significant decreased risk of serous ovarian cancer but not mucinous or other ovarian tumors . Conclusion . In accordance with most previous studies , our results indicate a possible inverse association between analgesic use , particularly aspirin , and ovarian cancer risk STUDY QUESTION Does cervical conization add an additional risk of preterm birth ( PTB ) in assisted reproduction technology ( ART ) singleton and twin pregnancies ? SUMMARY ANSWER Cervical conization doubles the risk of preterm and very PTB in ART twin pregnancies . WHAT IS KNOWN ALREADY ART and cervical conization are both risk factors for PTB . STUDY DESIGN , SIZE , DURATION In this national population -based controlled cohort study , we included all ART singletons and twin deliveries from 1995 to 2009 in Denmark by cross-linkage of maternal and child data from the National IVF register and the Medical Birth register . Furthermore , control groups of naturally conceived ( NC ) singletons and twins were extracted . Cervical diagnoses were obtained from the Danish Pathology register . Cervical conization included both cold knife cone and LEEP ( loop electrosurgical excision procedure ) but not cervical biopsies . The main outcomes measures were PTB ( PTB ≤ 37 + 0 gestational weeks ) , very preterm birth ( VPTB ≤ 32 + 0 gestational weeks ) and preterm premature rupture of membranes ( PPROM ) . PARTICIPANTS / MATERIAL S , SETTING , METHODS In all 16 923 ART singletons and 4829 ART twin deliveries were included . A r and om sample of NC singletons , 2-fold the size of the ART singleton group matched by date and year of birth ( n = 33 835 ) and all NC twin deliveries ( n = 15 112 ) , was also extracted . Multiple logistic regression analyses were performed to adjust for the following confounders : maternal age , parity , year of child birth and sex of child . MAIN RESULTS AND THE ROLE OF CHANCE Cervical morbidity ( dysplasia and conization ) was more often observed in ART pregnancies ( 6.2 % of ART singletons and 5.4 % ART twins ) than in NC pregnancies ( 4.2 % for NC singletons and 4.5 % for NC twins ) , both for singletons and twins . In ART singleton deliveries , the PTB rate was 13.1 versus 8.2 % in women with and without conization , respectively , with an adjusted odds ratio ( aOR ) of 1.56 [ 95 % confidence interval ( CI ) 1.21 - 2.01 ] . In ART twin deliveries , the prevalence of PTB was 58.2 versus 41.3 % in women with and without conization , respectively , with an aOR 1.94 ( 95 % CI 1.36 - 2.77 ) , and the risk of VPTB was also doubled . Furthermore , previous dysplasia ( without conization ) increased the risk of VPTB in ART twins ( aOR 1.74 , 95 % CI 1.04 - 2.94 ) . Cervical dysplasia did not increase the risk of any of the other adverse outcomes in ART singletons or twins . The risk of PPROM was increased in both in ART and NC singleton deliveries with conization versus no conization ; however , this increased risk of PPROM after conization was not observed in either ART or NC twin pregnancies . LIMITATIONS , REASONS FOR CAUTION We were not able to adjust for the height of the cervical cone or the severity of the cervical intraepithelial neoplasia ( CIN ) or the time window between diagnosis of CIN and ART treatment . The finding on an increased risk of VPTB in ART twin pregnancies after dysplasia without conization may be r and om as we found no other increased risk after dysplasia alone either in singletons or in twins . WIDER IMPLICATION S OF THE FINDINGS After ART and prior conization , 58 % of twin pregnancies versus 13 % of ART singleton pregnancies result in PTB . There is a doubled risk of preterm delivery in ART twins with conization versus ART twins with no prior conization . Single-embryo transfer should always be recommended in women with prior conization irrespective of female age , embryo quality and prior number of ART attempts . STUDY FUNDING /COMPETING INTERESTS No external funding was achieved for this project BACKGROUND Comorbidity is common in head and neck squamous cell carcinoma ( HNSCC ) patients due to the etiology of the disease being primarily smoking . The aim of this study was to investigate the impact of comorbidity on survival in a national population -based cohort study on 9388 HNSCC- patients treated with radiotherapy ( RT ) , to re-evaluate the prognostic impact of individual diseases within the Charlson Comorbidity Index ( CCI ) , and to develop a revised head and neck comorbidity index ( HN-CCI ) . MATERIAL AND METHODS A national cohort of 9388 HNSCC- patients treated with curative intended RT diagnosed from 1992 to 2008 was identified from the DAHANCA- data base . Data on comorbidity prior to HNSCC-diagnosis was obtained from the National Patient Registry and adapted to the CCI . RESULTS By dividing the patients into two groups , we tested and vali date d which type of comorbidities within the CCI affected overall survival ( OS ) and cancer specific death ( CSD ) . In total , 36 % of patients had comorbidity . Six comorbid conditions within the CCI significantly reduced five-year OS probability : congestive heart failure , cerebrovascular disease , chronic pulmonary disease , peptic ulcer disease , liver disease , and diabetes , and based on these conditions the new head and neck specific comorbidity index was developed , the HN-CCI . Comorbidity according to HN-CCI had a highly significant impact on OS , whereas it was not associated with CSD . Chronological age was not associated with increased risk of CSD after controlling for comorbidity . CONCLUSIONS Comorbidity is frequent in HNSCC patients and negatively impacts OS . Therefore assessment of comorbidity will be of great importance , both in order to treat/optimize patient 's health before radiotherapy , but also in order to be able to stratify/control for comorbidity in r and omized trials to avoid bias . Re-evaluation of the CCI revealed that only six conditions had an impact on survival , and a new modified index to assess comorbidity for HNSCC- patients was developed . The performance of HN-CCI to stratify patients on survival was good and HN-CCI is highly recommended for future assessment of comorbidity and prognostic staging of radiotherapy-treated HNSCC- patients INTRODUCTION Contemporary state-of-the-art management of cancer is increasingly defined by individualized treatment strategies . For very rare tumors , like hepatoblastoma , the development of biologic markers , and the identification of reliable prognostic risk factors for tailoring treatment , remains very challenging . The Children 's Hepatic tumors International Collaboration ( CHIC ) is a novel international response to this challenge . METHODS Four multicenter trial groups in the world , who have performed prospect i ve controlled studies of hepatoblastoma over the past two decades ( COG ; SIOPEL ; GPOH ; and JPLT ) , joined forces to form the CHIC consortium . With the support of the data management group CINECA , CHIC developed a central ized online platform where data from eight completed hepatoblastoma trials were merged to form a data base of 1605 hepatoblastoma cases treated between 1988 and 2008 . The result ing data set is described and the relationships between selected patient and tumor characteristics , and risk for adverse disease outcome ( event-free survival ; EFS ) are examined . RESULTS Significantly increased risk for EFS-event was noted for advanced PRETEXT group , macrovascular venous or portal involvement , contiguous extrahepatic disease , primary tumor multifocality and tumor rupture at enrollment . Higher age ( ≥ 8 years ) , low AFP ( < 100 ng/ml ) and metastatic disease were associated with the worst outcome . CONCLUSION We have identified novel prognostic factors for hepatoblastoma , as well as confirmed established factors , that will be used to develop a future common global risk stratification system . The mechanics of developing the globally accessible web-based portal , building and refining the data base , and performing this first statistical analysis has laid the foundation for future collaborative efforts . This is an important step for refining of the risk based grouping and approach to future treatment stratification , thus we think our collaboration offers a template for others to follow in the study of rare tumors and diseases The National Institute of Child Health and Human Development conducts and supports research on all stages of human development from preconception to adulthood in order to better underst and the health of children , youths , adults , families , and communities . Health and human development information is made easily available on the site with a simple A to Z list , along with clinical trials and health education campaign information . Links to clinical trials , news releases , publications , and related web sites are also available , as well as information on research being conducted at present and supported by the National Institute of Child Health and Human Development Abstract Background . The post-treatment follow-up is well-integrated in the oncologic care tradition , based on the risk of developing recurrent disease or new primary tumors in treated patients . Furthermore , follow-up serves as an opportunity to monitor treatment effects and to provide clinical care of side effects . In this study we measured the activity and effectiveness of routine follow-up in head and neck cancer and assessed the value of follow-up from the perspectives of both physicians and the patients . Patients and methods . During a period of six weeks a prospect i ve national cross section cohort of 619 patients attending regular follow-up were enrolled . All patients had received intended curative treatment for head and neck cancer and all were followed according to DAHANCA guidelines . Data were collected by the physician filling in a registration form containing chosen key parameters and patients filling in a vali date d question naire . Results . The majority ( 91 % ) of the 619 visits was planned , and 75 % of all visits included either tumor or treatment-related problems . Suspicion of recurrent disease led to further diagnostic work-up in 80 visits ( 13 % ) . A total of 29 recurrences were found , and of these seven ( 25 % ) were asymptomatic , i.e. the “ number needed to see ” to detect one asymptomatic recurrence was 99 . Treatment-related normal-tissue problems were addressed in 72 % of all visits , and among these 18 % required intervention . Although the majority of problems ( either suspicion of recurrent disease or late effects ) occurred within a few years after treatment , 39 % of patients seen after three years also had problems . The majority of patients ( 97 % ) expressed satisfaction with the planned follow-up . Conclusion . Only few relapses are found in asymptomatic patients at routine follow-up , with one silent recurrence detected per 99 visits . However , head and neck cancer survivors have a substantial need for management of sequelae . In this context , a central ized routine follow-up may still be worthwhile Rationale : The weaning process concerns all patients receiving mechanical ventilation . A previous classification into simple , prolonged , and difficult weaning ignored weaning failure and presupposed the use of spontaneous breathing trials . Objectives : To describe the weaning process , defined as starting with any attempt at separation from mechanical ventilation and its prognosis , according to a new operational classification working for all patients under ventilation . Methods : This was a multinational prospect i ve multicenter observational study over 3 months of all patients receiving mechanical ventilation in 36 intensive care units , with daily collection of ventilation and weaning modalities . Pragmatic definitions of separation attempt and weaning success allowed us to allocate patients in four groups . Measurements and Main Results : A total of 2,729 patients were enrolled . Although half of them could not be classified using the previous definition , 99 % entered the groups on the basis of our new definition as follows : 24 % never started a weaning process , 57 % had a weaning process of less than 24 hours ( group 1 ) , 10 % had a difficult weaning of more than 1 day and less than 1 week ( group 2 ) , and 9 % had a prolonged weaning duration of 1 week or more ( group 3 ) . Duration of ventilation , intensive care unit stay , and mortality ( 6 , 17 , and 29 % for the three groups , respectively ) all significantly increased from one group to the next . The unadjusted risk of dying was 19 % after the first separation attempt and increased to 37 % after 10 days . Conclusions : A new classification allows us to categorize all weaning situations . Every additional day without a weaning success after the first separation attempt increases the risk of dying BACKGROUND Patient-self-management ( PSM ) of oral anticoagulant therapy with vitamin K antagonists for mechanical heart valves has demonstrated efficacy in r and omized controlled trials . However , the effectiveness of PSM in clinical practice has only been investigated in small trials . Our aim was to evaluate the effectiveness of PSM of oral anticoagulant therapy in mechanical heart valve patients . METHODS We conducted a matched cohort study : cases were patients with a mechanical heart valve performing PSM affiliated with Aarhus University Hospital or Aalborg University Hospital , Denmark , in the period 1996 to 2012 ( n = 615 ) . Prospect ively registered patient data were obtained from data bases at two hospitals , and cross linkage between these data bases and national patient registries provided detailed information on comorbidities and events . Control patients were matched ( on sex , date of birth , year of first valve surgery , and grouped valve position ) in a ratio of 5:1 ( n = 3,075 ) with patients receiving conventional management who were r and omly selected within the match group . The effectiveness and safety was estimated using major bleeding and thromboembolic events and death as outcomes . RESULTS We observed low event rates in the PSM group . After 5 years , PSM was associated with a lower risk of all-cause mortality compared with conventional management ( adjusted hazard ratio of 0.49 , 95 % confidence interval : 0.34 to 0.71 ) . The hazard ratios for thromboembolism and major bleeding were 0.91 ( 95 % confidence interval : 0.66 to 1.24 ) and 0.83 ( 95 % confidence interval : 0.56 to 1.22 ) . CONCLUSIONS Owing to superior clinical effectiveness , self-managed oral anticoagulant therapy may potentially improve the st and ard of care for patients with mechanical heart valves BACKGROUND Surgical risk scores , such as the logistic EuroSCORE ( LES ) and Society of Thoracic Surgeons Predicted Risk of Mortality ( STS ) score , are commonly used to identify high-risk or " inoperable " patients for transcatheter aortic valve implantation ( TAVI ) . In Europe , the LES plays an important role in selecting patients for implantation with the Medtronic CoreValve System . What is less clear , however , is the role of the STS score of these patients and the relationship between the LES and STS . OBJECTIVE The purpose of this study is to examine the correlation between LES and STS scores and their performance characteristics in high-risk surgical patients implanted with the Medtronic CoreValve System . METHODS All consecutive patients ( n = 168 ) in whom a CoreValve bioprosthesis was implanted between November 2005 and June 2009 at 2 centers ( Bern University Hospital , Bern , Switzerl and , and Erasmus Medical Center , Rotterdam , The Netherl and s ) were included for analysis . Patient demographics were recorded in a prospect i ve data base . Logistic EuroSCORE and STS scores were calculated on a prospect i ve and retrospective basis , respectively . RESULTS Observed mortality was 11.1 % . The mean LES was 3 times higher than the mean STS score ( LES 20.2 % + /- 13.9 % vs STS 6.7 % + /- 5.8 % ) . Based on the various LES and STS cutoff values used in previous and ongoing TAVI trials , 53 % of patients had an LES > or = 15 % , 16 % had an STS > or = 10 % , and 40 % had an LES > or = 20 % or STS > or = 10 % . Pearson correlation coefficient revealed a reasonable ( moderate ) linear relationship between the LES and STS scores , r = 0.58 , P < .001 . Although the STS score outperformed the LES , both models had suboptimal discriminatory power ( c-statistic , 0.49 for LES and 0.69 for STS ) and calibration . CONCLUSIONS Clinical judgment and the Heart Team concept should play a key role in selecting patients for TAVI , whereas currently available surgical risk score algorithms should be used to guide clinical decision making Aim To compare 14 and 24 weeks treatment to patients with HCV genotype 2 or 3 infection and rapid virological response ( RVR ) . Material s and methods Patients included in two Sc and inavian trials , one nonr and omized pilot trial ( n=122 ) and one r and omized controlled trial ( RCT ) ( n=428 ) were entered into a pooled data base . In both trials treatment naïve patients with genotype 2 or 3 were treated with pegylated interferon alpha 2b ( 1.5 μg/kg , subcutaneous ) weekly and ribavirin ( 800–1400 mg , orally ) daily . Primary endpoint was sustained virological response ( SVR ) . RVR was defined as HCV RNA less than 50 IU/ml after 4 weeks of treatment . In the pilot trial all patients with RVR were treated for 14 weeks and in the RCT patients with RVR were r and omised to either 14 or 24 weeks treatment . Patients treated per protocol were included in the primary analysis . The noninferiority margin was set to be 10 % between the two groups with a one-sided 5 % significance level . Results In patients with RVR and genotype 2 or 3 SVR was obtained in 181 of 199 ( 91.0 % ) and 93 of 98 ( 94.9 % ) after 14 and 24 weeks treatment , respectively . The observed difference in SVR rates was 3.9 % ( 90 % confidence interval : + 1 to −8.8 ) . The relapse rate was highest among those older than 40 years and those with genotype 3 and high viral load , but prolongation of treatment from 14 to 24 weeks did not reduce the relapse rate substantially in any of these groups . Conclusion In patients with HCV genotype 2 or 3 infection and RVR 14 weeks treatment is noninferior to 24 weeks Purpose Occupational exposure of firefighters involves a complex range of potential health threats from toxic chemicals , shift work , extreme heat , physical and emotional strain . The aim of this study is to examine overall and disease-specific mortality among Danish firefighters . Methods Through systematic collection of personnel and membership records from employers and trade unions , past and present male Danish firefighters were identified ( n = 11,775 ) . Using the unique Danish personal identification number , information on additional employment , vital status and cause of death was linked to each member of the cohort from the Supplementary Pension Fund Register , the Danish Civil Registration System and the Danish Register of Causes of Death . St and ardized mortality ratios ( SMRs ) were calculated for specific causes of death using rates for two reference groups , a r and om sample of the male working population ( n = 262,168 ) and the military ( n = 396,739 ) , respectively . Results Overall mortality was significantly reduced among the firefighters compared to both the sample of the working population and the military ( SMR 0.74 , 95 % CI 0.69–0.78 and SMR 0.88 , 95 % CI 0.83–0.93 ) . Further , the SMRs for endocrine diseases , mental disorders , non-traffic related accidents and other external causes were significantly lower against both reference groups . Death from stomach cancer was significantly increased among the full time firefighters , while part time/volunteer workers shared a significant increase in prostate cancer death compared to both references . Conclusions Despite potential exposure to several occupational hazards , male Danish firefighters have a lower mortality than both the Danish working population in general and Danish military employees BACKGROUND Discussion regarding the necessity to identify patients with both the need and motivation for psychosocial intervention is ongoing . Evidence for an effect of mindfulness-based interventions among cancer patients is based on few studies with no systematic enrollment . METHODS We used Danish population -based registries and clinical data bases to determine differences in demographics , breast cancer and co-morbidity among 1208 women eligible for a r and omized controlled trial ( www . clinical trials.gov identifier : NCT00990977 ) of mindfulness-based stress reduction MBSR . RESULTS Participants ( N = 336 ) were found to be younger ( p < 0.001 ) and have a less recent diagnosis at invitation than decliners ( N = 872 ; p < 0.001 ) . After adjustment for age and time since diagnosis at invitation , a statistically significant difference was also found between the two groups in use of psychologist sessions ( p < 0.05 ) , whereas neither breast cancer variables nor co-morbidity was significantly different . Self-reported data obtained by use of vali date d psychometric scales from 169 decliners and 336 women who agreed to enroll in the trial showed statistically significant differences in level of education , distress , anxiety , depression , well being and symptom burden . No differences were observed with regard to marital status , children living at home , affiliation to the work market , psychiatric caseness or any lifestyle measure . CONCLUSION Our findings indicate that participants are younger , have a less recent diagnosis and have a higher level of education than those who refuse . This should be taken into account in design ing and evaluating trials of psychosocial interventions and in planning mindfulness-based interventions A total of 156 patients ( age range 1.3–18.0 years , median 13.2 years ; 91 ( 58.3 % ) male ) with newly diagnosed CML ( N = 146 chronic phase ( CML-CP ) , N = 3 accelerated phase ( CML-AP ) , N = 7 blastic phase ( CML-BP ) ) received imatinib up-front ( 300 , 400 , 500 mg/m2 , respectively ) within a prospect i ve phase III trial . Therapy response , progression-free survival , causes of treatment failure , and side effects were analyzed in 148 children and adolescents with complete data . Event-free survival rate by 18 months for patients in CML-CP ( median follow-up time 25 months , range : 1−120 ) was 97 % ( 95 % CI , 94.2−99.9 % ) . According to the 2006 ELN- criteria complete hematologic response by month 3 , complete cytogenetic response ( CCyR ) by month 12 , and major molecular response ( MMR ) by month 18 were achieved in 98 , 63 , and 59 % of the patients , respectively . By month 36 , 86 % of the patients achieved CCyR and 74 % achieved MMR . Thirty-eight patients ( 27 % ) experienced imatinib failure because of unsatisfactory response or intolerance ( N = 9 ) . In all , 28/148 patients ( 19 % ) underwent stem cell transplantation ( SCT ) . In the SCT sub-cohort 2/23 patients diagnosed in CML-CP , 0/1 in CML-AP , and 2/4 in CML-BP , respectively , died of relapse ( N = 3 ) or SCT-related complications ( N = 2 ) . This large pediatric trial extends and confirms data from smaller series that first-line imatinib in children is highly effective Background The application of rehabilitation robots has grown during the last decade . While meta-analyses have shown beneficial effects of robotic interventions for some patient groups , the evidence is less in others . We established the Advanced Robotic Therapy Integrated Centers ( ARTIC ) network with the goal of advancing the science and clinical practice of rehabilitation robotics . The investigators hope to exploit variations in practice to learn about current clinical application and outcomes . The aim of this paper is to introduce the ARTIC network to the clinical and research community , present the initial data set and its characteristics and compare the outcome data collected so far with data from prior studies . Methods ARTIC is a pragmatic observational study of clinical care . The data base includes patients with various neurological and gait deficits who used the driven gait orthosis Lokomat ® as part of their treatment . Patient characteristics , diagnosis-specific information , and indicators of impairment severity are collected . Core clinical assessment s include the 10-Meter Walk Test and the Goal Attainment Scaling . Data from each Lokomat ® training session are automatically collected . Results At time of analysis , the data base contained data collected from 595 patients ( cerebral palsy : n = 208 ; stroke : n = 129 ; spinal cord injury : n = 93 ; traumatic brain injury : n = 39 ; and various other diagnoses : n = 126 ) . At onset , average walking speeds were slow . The training intensity increased from the first to the final therapy session and most patients achieved their goals . Conclusions The characteristics of the patients matched epidemiological data for the target population s. When patient characteristics differed from epidemiological data , this was mainly due to the selection criteria used to assess eligibility for Lokomat ® training . While patients included in r and omized controlled interventional trials have to fulfill many inclusion and exclusion criteria , the only selection criteria applying to patients in the ARTIC data base are those required for use of the Lokomat ® . We suggest that the ARTIC network offers an opportunity to investigate the clinical application and effectiveness of rehabilitation technologies for various diagnoses . Due to the st and ardization of assessment s and the use of a common technology , this network could serve as a basis for research ers interested in specific interventional studies exp and ing beyond the Lokomat ® Objective The benefit of continuing 5-aminosalicylate ( 5-ASA ) in patients with ulcerative colitis ( UC ) who initiate anti-tumour necrosis factor-alpha ( anti-TNF ) biologics is unknown . We aim ed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA . Design Our primary outcome was any adverse clinical event defined as a composite of new corticosteroid use , UC-related hospitalisation or surgery . We used two national data bases : the United States ( US ) Truven MarketScan health cl aims data base and the Danish health registers . Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included . Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF . We performed multivariable Cox regression models controlling for demographics , clinical factors and healthcare utilisation . Adjusted HRs ( aHR ) with 95 % CI are reported comparing stopping 5-ASA with continuing 5-ASA . Results A total of 3589 patients with UC were included ( 2890 US and 699 Denmark ) . Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort ( aHR 1.04 ; 95 % CI 0.90 to 1.21 , p=0.57 ) nor in the Danish cohort ( aHR 1.09 ; 95 % CI 0.80 to 1.49 , p=0.60 ) . Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF . Conclusion In two national data bases , stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events . These results should be vali date d in a prospect i ve clinical trial Background and purpose — Acute myocardial infa rct ion ( MI ) is a leading cause of mortality following total hip and knee arthroplasty ( THA/TKA ) . The reported 30-day incidence of MI varies from 0.3 % to 0.9 % . However , most data derive from administration and insurance data bases or large RCTs with potential confounding factors . We studied the incidence of and potential modifiable risk factors for postoperative MI in a large , multicenter optimized “ fast-track ” THA/TKA setting . Patients and methods — A prospect i ve cohort study was conducted on consecutive unselected elective primary unilateral THA and TKA , using prospect i ve information on comorbidities and complete 90-day follow-up from the Danish National Patient Registry . Evaluation of discharge summaries and medical records was undertaken in cases of suspected MI . Logistic regression analyses were carried out for identification of preoperative risk factors . Results — Of 24,862 procedures with a median length of stay 2 ( IQR 2–3 ) days , 30- and 90-day incidence of MI was 31 ( 0.12 % ) and 48 ( 0.19 % ) . Preoperative risk factors for MI ≤30 days were age > 85 years ( OR 7.4 , 95 % CI 2.3–24 ) , insulin-dependent diabetes mellitus ( IDDM ) ( 3.6 , CI 1.1–12 ) , cardiovascular disease ( 2.4 , CI 1.1–5.0 ) and hypercholesterolemia ( 2.3 , CI 1.1–5.1 ) . Of 31 patients with MI ≤30 days 9 were treated with vasopressors for intraoperative hypotension and 27 had postoperative anemia . Interpretation — Fast-track THA and TKA had a low 30-day MI incidence . Focus on patients with age > 85 , IDDM , cardiovascular disease , and hypercholesterolemia may further reduce the 30-day incidence of MI . The role of postoperative anemia and intraoperative hypotension are other areas for further Background Survival and quality of life for patients affected by spinal muscular atrophy ( SMA ) are thought to have improved over the last decade due to changes in care . In addition , targeted treatments for SMA have been developed based on a better underst and ing of the molecular pathology . In 2016 and 2017 , nusinersen was the first drug to be approved for treatment of all types of SMA in the United States and in Europe based on well-controlled clinical trials in a small subgroup of pediatric SMA patients . Systems are required to monitor treated and untreated SMA patients in a real-life environment to optimize treatment and care , and to provide outcome data to regulators , payers , and the SMA community . Methods Within SMArtCARE , we conduct a prospect i ve , multicenter non-r and omized registration and outcome study . SMArtCARE collects longitudinal data on all available SMA patients independent of their actual treatment regime as disease-specific SMA registry . For this purpose , we provide an online platform for SMA patients seen by health-care providers in Germany , Austria and Switzerl and . All data are collected during routine patient visits . Items for data collection are aligned with the international consensus for SMA registries . Data analysis is carried out independent of commercial partners . Conclusion A prospect i ve monitoring of all SMA patients will lead to a better underst and ing of the natural history of SMA and the influence of drug treatment . This is crucial to improve the care of SMA patients . Further , we will establish a network for neuromuscular centers to share experience with SMA patients and to promote research projects on SMA.Trial registration German Clinical Trials Register ( “ Deutsches Register klinischer Studien ” ) DRKS00012699 . Registered 09 August 2018 . https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012699 OBJECTIVES Minimally invasive video-assisted thoracic surgery ( VATS ) was first introduced in the early 1990s . For decades , numerous non-r and omized studies demonstrated advantages of VATS over thoracotomy with lower morbidity and shorter hospital stay , but only recently did a r and omized trial document that VATS results in lower pain scores and better quality of life . Opposing arguments for VATS have always been increased costs and concerns about oncological adequacy . In this paper , we aim to investigate the cost-effectiveness of VATS . METHODS The study was design ed as a cost-utility analysis of the first 12 months following surgery and was performed together with a clinical r and omized controlled trial of VATS versus thoracotomy for lobectomy of stage 1 lung cancer during a 6-year period ( 2008 - 2014 ) . All health-related expenses were retrieved from a national data base ( Statistics Denmark ) including hospital readmissions , outpatient clinic visits , prescription medication costs , consultations with general practitioners , specialists , physiotherapists , psychologists and chiropractors . RESULTS One hundred and three VATS patients and 103 thoracotomy patients were r and omized . Mean costs per patient operated by VATS were 103 108 Danish Kroner ( Dkr ) ( € 13 818 ) and 134 945 Dkr ( € 18 085 ) by thoracotomy , making the costs for VATS 31 837 Dkr ( € 4267 ) lower than thoracotomy ( P < 0.001 ) . The difference in quality -adjusted life years gained over 52 weeks of follow-up was 0.021 ( P = 0.048 , 95 % confidence interval -0.04 to -0.00015 ) in favour of VATS . The median duration of the surgical procedure was shorter after thoracotomy ( 79 vs 100 min ; P < 0.001 ) . The mean length of hospitalization was shorter following VATS ( 4.8 vs 6.7 days ; P = 0.027 ) . The use of other re sources was not significantly different between groups . The costs of re sources were lower in the VATS group . This difference was primarily due to reduced costs of readmissions ( VATS 29 247 Dkr vs thoracotomy 51 734 Dkr ; P < 0.001 ) and costs of outpatient visits ( VATS 51 412 Dkr vs thoracotomy 61 575 Dkr ; P = 0.012 ) . CONCLUSIONS VATS is a cost-effective alternative to thoracotomy following lobectomy for stage 1 lung cancer . Economical outcomes as measured by quality -adjusted life years were significantly better and overall costs were lower for VATS . CLINICAL TRIAL REGISTRATION NUMBER NCT01278888 Study Design . Prospect i ve , multicenter cohort study including 8 medical centers of the Cantons Zurich , Lucerne , and Thurgau , Switzerl and . Objective . The aim of the study was to assess whether obese patients benefit after decompression surgery for degenerative lumbar spinal stenosis ( DLSS ) . Summary and Background Data . Lumbar decompression surgery has been shown to improve quality of life in patients with DLSS . In the existing literature , the efficacy of lumbar decompression in the obese population remains controversial . Methods . Baseline patient characteristics and outcomes were analyzed at 6 and 12 months follow-up with the Spinal Stenosis Measure ( SSM ) , the Numeric Rating Scale ( NRS ) , Feeling Thermometer ( FT ) , the EQ-5D-EL , and the Rol and and Morris Disability Question naire ( RMDQ ) . Body mass index ( BMI ) was classified into 3 categories according to the WHO . Minimal clinical ly important differences ( MCIDs ) in SSM for different BMI categories were considered as main outcome . Results . Of the 656 patients in the Lumbar Spinal Outcome Study data base as of end of October 2014 , 166 patients met the inclusion criteria . Fifty ( 30.1 % ) had a BMI less than 25 ( underweight and normal weight group ) , 72 ( 43.4 % ) had a BMI between 25 and less than 30 ( preobesity group ) , and 44 ( 26.5 % ) patients had a BMI at least 30 ( obese group ) . We found for the main outcome that in obese patients 36 % reached MCID at 6 months , and 48 % at 12 months . The estimated odds ratios for MCID in the obese group were 0.78 ( 0.34–1.82 ) at 6 months and 0.99 ( 0.44–2.23 ) at 12 months in a logistic regression model adjusting for levels of laminectomy . In the additional outcomes , SSM , NRS , FT , and RMDQ showed statistically significant mean improvements in the 6 and 12 months follow-up . Conclusion . Obese patients can expect clinical improvement after lumbar decompression for DLSS , but the percentage of patients with a meaningful improvement is lower than in the group of patients with underweight , normal weight , and preobese weight at 6 and 12 months |
10,303 | 25,139,841 | Exploratory subgroup analysis showed no effect of tumor types on the RR of ORR .
Our meta- analysis has demonstrated that cetuximab-induced rash is associated with a significantly improved OS , PFS and ORR .
Cetuximab-induced skin rash may represent a prognostic factor in patients with advanced solid tumors | BACKGROUND We performed a systematic review and meta- analysis of the correlation between cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab . | BACKGROUND Pre clinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor , EGFR antibody , and /or anti-angiogenic agent is synergistic in animal models . METHODS We conducted a dose-escalation , phase I study combining erlotinib , cetuximab , and bevacizumab . The subset of patients with non-small cell lung cancer ( NSCLC ) was analyzed for safety and response . RESULTS Thirty-four patients with NSCLC ( median four prior therapies ) received treatment on a range of dose levels . The most common treatment-related grade ≥2 adverse events were rash ( n=14 , 41 % ) , hypomagnesemia ( n=9 , 27 % ) , and fatigue ( n=5 , 15 % ) . Seven patients ( 21 % ) achieved stable disease ( SD ) ≥6 months , two achieved a partial response ( PR ) ( 6 % ) , and two achieved an unconfirmed partial response ( uPR ) ( 6 % ) ( total=32 % ) . We observed SD≥6 months/PR/uPR in patients who had received prior erlotinib and /or bevacizumab , those with brain metastases , smokers , and patients treated at lower dose levels . Five of 16 patients ( 31 % ) with wild-type EGFR experienced SD≥6 months or uPR . Correlation between grade of rash and rate of SD≥6 months/PR was observed ( p<0.01 ) . CONCLUSION The combination of erlotinib , cetuximab , and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC PURPOSE To evaluate the efficacy and safety of cetuximab , a monoclonal antibody that inhibits the epidermal growth factor receptor ( EGFR ) , as a first-line monotherapy in patients with unresectable squamous cell carcinoma of the skin ( SCCS ) . PATIENTS AND METHODS Thirty-six patients received cetuximab ( initial dose of 400 mg/m(2 ) followed by subsequent weekly doses of 250 mg/m(2 ) ) for at least 6 weeks with a 48-week follow-up . The primary end point was the disease control rate ( DCR ) at 6 weeks ( according to Response Evaluation Criteria in Solid Tumors [ RECIST ] criteria ) . Secondary end points included best response rate , overall survival , progression-free survival ( PFS ) , and toxicity assessment . Association of treatment efficacy with RAS mutations or FcγR genotypes was investigated . RESULTS Median age of the study population was 79 years . DCR at 6 weeks was obtained in 25 of 36 patients ( 69 % ; 95 % CI , 52 % to 84 % ) of the intention-to-treat population . The best responses were eight partial responses and two complete responses . There were no cetuximab-related deaths . There were three related serious adverse events : two grade 4 infusion reactions and one grade 3 interstitial pneumopathy . Grade 1 to 2 acne-like rash occurred in 78 % of patients and was associated with prolonged PFS . One HRAS mutation was identified . Combined FcγRIIa-131H/H and /or FcγRIIIa-158V/V polymorphisms were not associated with the clinical outcomes . CONCLUSION As a first-line treatment in patients with unresectable SCCS , cetuximab achieved 69 % DCR . A r and omized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option especially in elderly patients . The low frequency of RAS mutations in SCCS makes SCCS tumors attractive for EGFR inhibition BACKGROUND According to the results of a number of phase 3 r and omized studies , sorafenib is the only approved systemic therapy for advanced HCC ; however the issue of high economic cost remains challenging ; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib . METHODS HCC patients treated at Ain Shams University Hospitals , in the period between 2010 and 2012 were review ed . Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy . We investigated the impact of baseline clinicopathological factors ( age , gender , child status , performance score , BCLC tumor stage , cause of chronic liver disease , median baseline alpha fetoprotein level and previous treatment received for HCC ) on overall survival ( OS ) in an adjusted Cox regression model . RESULTS 41 patients were included in the analysis fulfilling the inclusion criteria . At a median follow up period of 13 months , the median PFS for the whole group was 4 months ; the median OS for the whole group is 6.25 months . Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival : ECOG performance status ( median OS for ECOG 1=7.01 months and for ECOG 2=3.03 months ) , Child-Pugh status ( median OS for child A=12.04 months and for child B=5.23 months ) , and median baseline levels of alpha-fetoprotein . CONCLUSIONS In limited re source countries like Egypt , we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child BACKGROUND The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma . PATIENTS AND METHODS Patients with failure to first-line platinum-based chemotherapy received cetuximab 500 mg/m(2 ) and irinotecan 180 mg/m(2 ) every second week until disease progression . Toxicity was evaluated according to The Cancer Institute Common Terminology Criteria for Adverse Events ( NCI-CTCAE ) v. 3.0 . Antitumour activity was assessed according to Response Evaluation Criteria in Solid Tumours ( RECIST ) v. 1.0 . RESULTS Sixty-three patients were enrolled , median age was 60 years , median performance status was 1 ( 0 - 1 ) , 35 patients had two or more organs involved . The median number of courses was 5 ( range 1 - 25 ) . Response rate was 11 % ( 6 partial response ( PR ) ) and 37 % had stable disease . Median progression free survival was 2.8 months and overall survival ( OS ) was 6.1 months . Grade 3 - 4 toxicity included : diarrhoea ( 6 % ) , fatigue ( 5 % ) , vomiting ( 5 % ) and neutropenia ( 16 % ) . Two patients developed febrile neutropenia . Forty-six patients ( 73 % ) had developed grade 1 - 2 skin rash . Patients developing skin rash had a prolonged survival with an OS at 7.1 months . CONCLUSIONS The combination of cetuximab and irinotecan is active as second-line therapy in patients with gastro-oesophageal cancer . Cetuximab induced skin rash was associated with prolonged survival The only approved systemic therapy for patients with advanced hepatocellular carcinoma ( HCC ) till now is sorafenib . A preliminary study suggested that capecitabine , an oral fluoropyrimidine , may be effective in advanced HCC . We have tested this hypothesis in this phase 2 study . In this single-center , phase 2 , open-label trial , we r and omly assigned 52 patients with advanced HCC who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or capecitabine ( 1,000 mg/m2 twice daily ) ( day 1–day 14 ) . Primary outcome was progression-free survival . Secondary outcomes included the overall survival and safety . Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the capecitabine group ( hazard ratio in the capecitabine group 2.36 ; 95 % confidence interval 1.174–4.74 ; P < 0.016 ) . The median progression-free survival was 6 months in the sorafenib group and 4 months in the capecitabine group ( P < 0.005 ) . Three patients in the sorafenib group ( 11.5 % ) and one patient in the capecitabine group ( 3 % ) had a partial response ; one patient ( 3 % ) had a complete response in the sorafenib group . H and –foot skin reaction was more frequent in the sorafenib group , hyperbilirubinemia was more common in the capecitabine group , and diarrhea was equivalent between both groups . In patients with advanced HCC , capecitabine is inferior to sorafenib in terms of median progression-free survival and overall survival , and it should not be used alone for the treatment of advanced HCC , but rather , combination therapy with sorafenib should be considered BACKGROUND Previous results from our phase 3 r and omised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck ( LASCCHN ) at 3 years . Here we report the 5-year survival data , and investigate the relation between cetuximab-induced rash and survival . METHODS Patients with LASCCHN of the oropharynx , hypopharynx , or larynx with measurable disease were r and omly allocated in a 1:1 ratio to receive either comprehensive head and neck radiotherapy alone for 6 - 7 weeks or radiotherapy plus weekly doses of cetuximab : 400 mg/m(2 ) initial dose , followed by seven weekly doses at 250 mg/m(2 ) . R and omisation was done with an adaptive minimisation technique to balance assignments across stratification factors of Karnofsky performance score , T stage , N stage , and radiation fractionation . The trial was un-blinded . The primary endpoint was locoregional control , with a secondary endpoint of survival . Following discussion s with the US Food and Drug Administration , the data set was locked , except for queries to the sites about overall survival , before our previous report in 2006 , so that an independent review could be done . Analyses were done on an intention-to-treat basis . Following completion of treatment , patients underwent physical examination and radiographic imaging every 4 months for 2 years , and then every 6 months thereafter . The trial is registered at www . Clinical Trials.gov , number NCT00004227 . FINDINGS Patients were r and omly assigned to receive radiotherapy with ( n=211 ) or without ( n=213 ) cetuximab , and all patients were followed for survival . Up date d median overall survival for patients treated with cetuximab and radiotherapy was 49.0 months ( 95 % CI 32.8 - 69.5 ) versus 29.3 months ( 20.6 - 41.4 ) in the radiotherapy-alone group ( hazard ratio [ HR ] 0.73 , 95 % CI 0.56 - 0.95 ; p=0.018 ) . 5-year overall survival was 45.6 % in the cetuximab-plus-radiotherapy group and 36.4 % in the radiotherapy-alone group . Additionally , for the patients treated with cetuximab , overall survival was significantly improved in those who experienced an acneiform rash of at least grade 2 severity compared with patients with no rash or grade 1 rash ( HR 0.49 , 0.34 - 0.72 ; p=0.002 ) . INTERPRETATION For patients with LASCCHN , cetuximab plus radiotherapy significantly improves overall survival at 5 years compared with radiotherapy alone , confirming cetuximab plus radiotherapy as an important treatment option in this group of patients . Cetuximab-treated patients with prominent cetuximab-induced rash ( grade 2 or above ) have better survival than patients with no or grade 1 rash . FUNDING ImClone Systems , Merck KGaA , and Bristol-Myers Squibb BACKGROUND The r and omised phase 3 First-Line Erbitux in Lung Cancer ( FLEX ) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . The main cetuximab-related side-effect was acne-like rash . Here , we assessed the association of this acne-like rash with clinical benefit . METHODS We did a subgroup analysis of patients in the FLEX study , which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor . Our l and mark analysis assessed if the development of acne-like rash in the first 21 days of treatment ( first-cycle rash ) was associated with clinical outcome , on the basis of patients in the intention-to-treat population alive on day 21 . The FLEX study is registered with Clinical Trials.gov , number NCT00148798 . FINDINGS 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash- and 540 patients in the chemotherapy alone group were alive on day 21 . Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash ( median 15·0 months [ 95 % CI 12·8 - 16·4 ] vs 8·8 months [ 7·6 - 11·1 ] ; hazard ratio [ HR ] 0·631 [ 0·515 - 0·774 ] ; p<0·0001 ) . Corresponding significant associations were also noted for progression-free survival ( median 5·4 months [ 5·2 - 5·7 ] vs 4·3 months [ 4·1 - 5·3 ] ; HR 0·741 [ 0·607 - 0·905 ] ; p=0·0031 ) and response ( rate 44·8 % [ 39·0 - 50·8 ] vs 32·0 % [ 26·0 - 38·5 ] ; odds ratio 1·703 [ 1·186 - 2·448 ] ; p=0·0039 ) . Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone ( median 8·8 months [ 7·6 - 11·1 ] vs 10·3 months [ 9·6 - 11·3 ] ; HR 1·085 [ 0·910 - 1·293 ] ; p=0·36 ) . The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups : adenocarcinoma ( median 16·9 months , [ 14·1 - 20·6 ] vs 9·3 months [ 7·7 - 13·2 ] ; HR 0·614 [ 0·453 - 0·832 ] ; p=0·0015 ) , squamous-cell carcinoma ( median 13·2 months [ 10·6 - 16·0 ] vs 8·1 months [ 6·7 - 12·6 ] ; HR 0·659 [ 0·472 - 0·921 ] ; p=0·014 ) , and carcinomas of other histology ( median 12·6 months [ 9·2 - 16·4 ] vs 6·9 months [ 5·2 - 11·0 ] ; HR 0·616 [ 0·392 - 0·966 ] ; p=0·033 ) . INTERPRETATION First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment . First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit |
10,304 | 17,386,336 | The Task Force concluded that the findings are applicable to MSM aged 20 years or older , across a range of setting s and population s , assuming that interventions are appropriately adapted to the needs and characteristics of the MSM population of interest .
Based on findings from economic evaluation studies , the Task Force also concluded that group- and community-level HIV behavioral interventions for adult MSM are not only cost effective but also result in actual cost savings . | This article presents the results of a systematic review of the effectiveness and economic efficiency of individual- , group- , and community-level behavioral interventions intended to reduce the risk of acquiring sexually transmitted HIV in adult men who have sex with men ( MSM ) .
These results form the basis for recommendations by the Task Force on Community Preventive Services on the use of these interventions . | Abstract Objective : To determine the effectiveness of a brief cognitive behavioural intervention in reducing the incidence of sexually transmitted infections among gay men . Design : R and omised controlled trial with 12 months ' follow up . Setting : Sexual health clinic in London . Participants : 343 gay men with an acute sexually transmitted infection or who reported having had unprotected anal intercourse in the past year . Main outcome measures : Number of new sexually transmitted infections diagnosed during follow up and self reported incidence of unprotected anal intercourse . Results : 72 % ( 361/499 ) of men invited to enter the study did so . 90 % ( 308/343 ) of participants returned at least one follow up question naire or re-attended the clinic and requested a check up for sexually transmitted infections during follow up . At baseline , 37 % ( 63/172 ) of the intervention group and 30 % ( 50/166 ) of the control group reported having had unprotected anal intercourse in the past month . At 12 months , the proportions were 27 % ( 31/114 ) and 32 % ( 39/124 ) respectively ( P=0.56 ) . However , 31 % ( 38/123 ) of the intervention group and 21 % ( 35/168 ) of controls had had at least one new infection diagnosed at the clinic ( adjusted odds ratio 1.66 , 95 % confidence interval 1.00 to 2.74 ) . Considering only men who requested a check up for sexually transmitted infections , the proportion diagnosed with a new infection was 58 % ( 53/91 ) for men in the intervention group and 43 % ( 35/81 ) for men in the control group ( adjusted odds ratio 1.84 , 0.99 to 3.40 ) . Using a regional data base that includes information from 23 sexual health clinics in London , we determined that few participants had attended other sexual health clinics . Conclusions : This behavioural intervention was acceptable and feasible to deliver , but it did not reduce the risk of acquiring a new sexually transmitted infection among these gay men at high risk . Even carefully design ed interventions should not be assumed to bring benefit . It is important to evaluate their effects in r and omised trials with objective clinical end points . What is already known on this topic The need for effective HIV prevention strategies based on reducing sexual risk behaviour remains important Few interventions to reduce sexual risk behaviour have been rigorously evaluated using r and omised controlled trials What this study adds This is the first r and omised controlled trial of an intervention addressing sexual behaviour in homosexual men that uses sexually transmitted infections and self reported behaviour as end points The intervention was brief and feasible to use in a busy clinic , but it did not reduce the risk of participants acquiring new infections The potential for behavioural interventions to do more harm than good needs to be taken BACKGROUND Effective interventions are needed to prevent acquisition of HIV infection in men who have sex with men . To date , no behavioural interventions specifically for this risk group have been tested with HIV infection as the primary outcome . METHODS This multisite two-group r and omised controlled phase IIb trial tested the efficacy of a behavioural intervention in preventing HIV infection among 4295 men who have sex with men . The experimental intervention consisted of ten one-on-one counselling sessions followed by maintenance sessions every 3 months . The st and ard condition was twice-yearly Project RESPECT individual counselling . Twice-yearly follow-up visits included testing for HIV antibody and assessment of behavioural outcomes . FINDINGS The rate of acquisition of HIV infection was 18.2 % ( 95 % CI -4.7 to 36.0 ) lower in the intervention group than the st and ard group . Adjustment for baseline covariates attenuated the intervention effect to 15.7 % ( -8.4 to 34.4 ) . The effect was more favourable in the first 12 - 18 months of follow-up . The occurrence of unprotected receptive anal intercourse with HIV-positive and unknown-status partners was 20.5 % ( 10.9 to 29.0 ) lower in the intervention than in the st and ard group . INTERPRETATION The results from the primary analyses allow us to rule out that the experimental intervention is associated with a 35 % lower rate of HIV acquisition than in the st and ard group . The overall estimate of a difference of 18.2 % , more favourable estimates of effect in the first 12 - 18 months , and similar effects on risk behaviours suggest that prevention of HIV infection among men who have sex with men by a behavioural intervention is feasible . Further work should be done to develop more effective interventions At the time of this writing , no r and omized controlled trial ( RCT ) of an intervention to reduce unsafe sex among Latino gay and bisexual men ( LGBM ) had been published . We report the results of an RCT conducted in New York City in which 180 LGBM were assigned either to an intervention developed specifically for this population or to a wait-list control group . The intervention was based on empowerment theory and used factors identified in prior research as determinants of unsafe sex . By eligibility criteria , all men had engaged in unprotected anal intercourse ( UAI ) within two months of the baseline assessment . At first ( two months ) and second ( six months later ) follow-up assessment s , approximately half of the men in the experimental group reported no UAI . Yet , a similar proportion of the control group also reported no UAI . Baseline data indicate that although the men had been the subject of social oppression and sexual prejudice ( homophobia ) , they did not feel disempowered , externally controlled or fatalistic , and they reported self-efficacy and intentionality to enact safer sex . Lessons learned are discussed , as well as notes of caution for future research employing a similar conceptual framework Objectives : To evaluate the effects of an enhanced peer-led intervention on transmission risk behavior and serostatus disclosure of HIV-seropositive gay and bisexual men . Design : A r and omized intervention trial . Methods : HIV-seropositive gay and bisexual men were recruited from New York City and San Francisco and were r and omly assigned to either a st and ard or an enhanced intervention . The st and ard intervention consisted of one session that provided safer sex information . The enhanced intervention consisted of six sessions and included safer sex information , interactive learning activities , and discussion groups that were facilitated by HIV-seropositive peers . Participants completed audio computer-assisted self interview ( A-CASI ) assessment s at baseline and 3 and 6-month follow-ups . Optional testing for sexually transmitted infections was offered at baseline and the 6-month follow-up . Results : A total of 811 participants met the inclusion criteria for outcome analyses . Of these , 85 and 90 % were retained for the 3 and 6-month follow-ups , respectively . Compared with the st and ard intervention , fewer men assigned to the enhanced intervention reported unprotected receptive anal intercourse with a negative or unknown-serostatus partner at 3 months ( 21 versus 26 % , P < 0.05 ) . However , there were no other significant differences in transmission risk or serostatus disclosure at 3 or 6 months . Conclusion : The enhanced intervention was associated with only a limited reduction in transmission risk at 3 months relative to the st and ard intervention . The characteristics of the intervention that may have reduced its efficacy are identified and directions for future research are suggested Behavior change can curtail the spread of acquired immune deficiency syndrome ( AIDS ) . In this study , 104 gay men with a history of frequent AIDS high-risk behavior completed self-report , self-monitoring , and behavioral measures related to AIDS risk . The sample was r and omly divided into experimental and waiting-list control groups . The experimental intervention provided AIDS risk education , cognitive-behavioral self-management training , sexual assertion training , and attention to the development of steady and self-affirming social supports . Experimental group participants greatly reduced their frequency of high-risk sexual practice s and increased behavioral skills for refusing sexual coercions , AIDS risk knowledge , and adoption of " safer sex " practice s. Change was maintained at the 8-month follow-up Objectives The incidence of AIDS is increasing at a higher rate among homosexual Asian and Pacific Isl and ers ( API ) than white homosexual men in the United States . The number of homosexual API men engaging in unsafe sex is increasing at an alarming rate . HIV risk reduction is urgently needed in this population . Subjects and methods We developed and evaluated culturally appropriate brief group counseling with 329 self-identified homosexual API recruited in San Francisco between 1992 and 1994 . Participants were r and omized into a single , 3-h skills training group or a wait-list control group . The intervention consisted of four components : ( 1 ) development of positive self-identity and social support , ( 2 ) safer sex education , ( 3 ) eroticizing safer sex , and ( 4 ) negotiating safer sex . Data were collected at baseline and 3 months after the intervention . Results Significant reductions in number of sexual partners were observed among all treatment subjects , regardless of ethnicity ( P= 0.003 ) . Treatment decreased the number of partners reported at 3-month follow-up by 46 % [ 95 % confidence interval ( CI ) , 28–77 ] . Chinese and Filipino men further benefited from the intervention : treatment subjects from these two ethnic groups reduced unprotected anal intercourse at follow-up by more than half when compared to their counterparts ( odds ratio = 0.41 ; 95 % CI , 0.19–0.89 ; P= 0.024 ) . Conclusions We demonstrated the efficacy of brief group counseling in reducing HIV risk among homosexual API . Cities with significant API population s should adopt culturally tailored skills training as part of HIV prevention strategies for this group of homosexual men This controlled prospect i ve study assessed the effectiveness of a sexual health approach to HIV prevention for men who have sex with men ( MSM ) . Participants ( N = 422 Midwestern MSM ) were r and omly assigned to the intervention group , who participated in a 2-day comprehensive human sexuality seminar design ed to context ually address long-term risk factors and cofactors , or to the control group , who watched 3 hours of HIV prevention videos . Risk behavior during the preceding 3 months was measured at baseline , 3-month follow-up , and 12-month follow-up . Any unprotected anal intercourse outside a long-term seroconcordant relationship was the dependent variable . Of the total , 14%-24 % of the participants were considered at risk of acquiring or transmitting HIV . At the 12-month follow-up , the control reported a 29 % decrease in the use of condoms during anal intercourse ; the intervention group reported an 8 % increase ( t = 2.546 ; p = .015 ) . The sexual health seminars appear a promising new intervention at significantly reducing unprotected anal intercourse between men HIV prevention , by intervening within social networks , is potentially important but highly understudied . Approaches that systematic ally identify , train , and enlist known social influence leaders to advise members of their own networks in risk reduction constitute ways to reach hidden population segments , persons who are distrustful of authorities but trust their peers , and those who can not be reached through traditional professionally delivered counseling . This article illustrates and provides evaluation data on a program that recruited 14 intact social networks of young men who have sex with men ( YMSM ) in St. Petersburg , Russia , and Sofia , Bulgaria . Sociometric measures were used to identify the social leader of each network , and baseline risk assessment measures were administered to all members of each social network . The sociometrically determined leaders then attended a six-session group program that provided training and guidance in how to carry out theory-based and tailored HIV prevention conversations with members of their own social networks . Four months after leaders completed the program , all network members were readministered risk assessment measures . Pre- to postintervention data revealed that the program produced : ( 1 ) increases in the level and comfort with which network members talked about AIDS prevention topics in their daily conversations ; ( 2 ) increased network-level AIDS risk reduction knowledge and improved risk reduction norm perceptions , attitudes , behavioral intentions , and self-efficacy ; and ( 3 ) increased condom use levels among network members . Although not a controlled , r and omized trial , these program evaluation findings strongly support the feasibility of social network-level HIV prevention approaches CONTEXT High-risk sexual behavior is increasingly prevalent among men who have sex with men ( MSM ) and among men with a history of repeat testing for HIV . OBJECTIVES The study assessed whether one counseling intervention session focusing on self-justifications ( thoughts , attitudes , or beliefs that allow the participant to engage in high-risk sexual behaviors ) at most recent unprotected anal intercourse ( UAI ) is effective in reducing future high-risk behaviors among HIV-negative men . DESIGN , SETTING , AND PARTICIPANTS A r and omized , controlled , counseling intervention trial was conducted at an anonymous testing site in San Francisco , California , between May 1997 and January 2000 . Participants were 248 MSM with a history of at least one previous negative HIV test result and self-reported UAI ( receptive or insertive ) in the previous 12 months with partners of unknown or discordant HIV status . Two intervention groups received st and ard HIV test counseling plus a cognitive-behavioral intervention , and two control groups received only st and ard HIV test counseling . Follow-up evaluation was at 6 and 12 months . MAIN OUTCOME MEASURE Number of episodes of UAI with non primary partners ( of unknown or discordant HIV status ) in the 90 days preceding the interview was measured via self-report during face-to-face interview . RESULTS A novel counseling intervention focusing on self-justifications significantly decreased the proportion of participants reporting UAI with non primary partners of unknown or discordant HIV status at 6 and 12 months ( from 66 % to 21 % at 6 months and to 26 % at 12 months , p = .002 ; p < .001 ) as compared with a control group when added to st and ard client-centered HIV counseling and testing . CONCLUSIONS A specific , single-session counseling intervention focusing on a reevaluation of a person 's self-justifications operant during a recent occasion of high-risk behavior may prove useful in decreasing individual risk behavior and thus limiting community-level HIV transmission OBJECTIVES We describe the prevalence of risk behaviors at baseline among men who have sex with men ( MSM ) who were enrolled in a r and omized behavioral intervention trial conducted in 6 US cities . METHODS Data analyses involved MSM who were negative for HIV antibodies and who reported having engaged in anal sex with 1 or more partners in the previous year . RESULTS Among 4295 men , 48.0 % and 54.9 % , respectively , reported unprotected receptive and insertive anal sex in the previous 6 months . Unprotected sex was significantly more likely with 1 primary partner or multiple partners than with 1 non primary partner . Drug and alcohol use were significantly associated with unprotected anal sex . CONCLUSIONS Our findings support the continued need for effective intervention strategies for MSM that address relationship status , serostatus of partners , and drug and alcohol use The same sexual behaviours that transmit HIV are implicated in the transmission of certain other STDs , including chlamydia , gonorrhoea , and syphilis . Consequently , it is often assumed that preventive methods that are effective against HIV should be equally effective against other STDs . The purpose of this study was to examine this assumption . We applied a mathematical model of HIV/STD transmission to empirical data from a large HIV prevention intervention that stressed sexual behaviour change . We modelled the effects of two behavioural strategies - reducing the number of sex partners and increasing condom use — on the proportionate change in intervention participants ' cumulative risk of acquiring HIV or a highly-infectious STD , such as gonorrhoea . The results of this modelling exercise indicate that decreasing the number of partners is a more effective strategy for reducing STD risk than it is for HIV risk . In contrast , condoms are somewhat more effective at reducing the cumulative transmission risk for HIV than for highly infectious STDs . The protection provided by condoms for multiple acts of intercourse critically depends on the infectiousness of the STD . The results of this study suggest caution in extrapolating from one STD to another , or from one behavioural risk reduction strategy to another This paper presents the first outcome evaluation of multi-session groupwork for HIV prevention among gay men in the UK . This community-based RCT recruited 50 men , of whom 42 % were HIV-positive or untested , and 32 % reported status unknown or serodiscordant UAI in the previous 12 months . No knowledge , skills , attitudinal or behavioural differences were detected between intervention and control at baseline . At eight weeks , those attending the group reported significant gains over their control in making sexual choices , physical safety , HIV and STI transmission knowledge , and sexual negotiation skills . At 20 weeks , significant differences remained for HIV and STI transmission knowledge and comfort with sexual choices . Although no behavioural differences were detected , the aims of the National Prevention Strategy were met . This pilot RCT is appraised in the light of modest sample size and attrition , and recommendations for establishing behavioural outcomes are presented . This study has demonstrated that high-risk community sample s can be recruited to multi-session interventions , and has provided feasibility data for future rigorous evaluation design BACKGROUND Community-level interventions may be helpful in population -focused HIV prevention . If members of population s at risk of HIV infection who are popular with other members can be engaged to advocate the benefits of behaviour change to peers , decreases in risk behaviour may be possible . We assessed a community-level intervention to lower the risk of HIV infection , focusing on men patronising gay bars in eight small US cities . METHODS We used a r and omised community-level field design . Four cities received the intervention and four control cities did not . Participants were men from each city who went to gay bars . Men completed surveys about their sexual behaviour on entering the bars during 3-night periods at baseline and at 1-year follow-up . In the control cities , HIV educational material s were placed in the bars . In the intervention cities , we recruited popular homosexual men in the community and trained them to spread behaviour-change endorsements and recommendations to their peers through conversation . FINDINGS Population -level of risk behaviour decreased significantly in the intervention cities compared with the control cities at 1-year follow-up , after exclusion of surveys completed by transients and men with exclusive sexual partners in a city-level analysis , in the intervention cities we found a reduction in the mean frequency of unprotected anal intercourse during the previous 2 months ( baseline 1.68 occasions ; follow-up 0.59 : p = 0.04 ) and an increase in the mean percentage of occasions of anal intercourse protected by condoms ( baseline 44.7 % ; follow-up 66.8 % , p = 0.02 ) . Increased numbers of condoms taken from dispensers in intervention-city bars corroborated risk-behaviour self-reports . INTERPRETATION Popular and well-liked members of a community who systematic ally endorse and recommend risk-reduction behaviour can influence the sexual-risk practice s of others in their social networks . Natural styles of communication , such as conversations , brought about population -level changes in risk behaviour OBJECTIVE Although many studies have documented patterns of emotional distress in persons with HIV disease , there have been few controlled evaluations of therapy outcomes with these individuals . This research evaluated the effects of brief cognitive-behavioral or social support group therapy with this population . METHOD Sixty-eight depressed men with HIV infection were r and omly assigned to one of three conditions : eight-session cognitive-behavioral groups , eight-session social support groups , or a comparison condition . Before and after intervention and at 3-month follow-up , all participants were individually assessed by using measures of symptoms of distress as well as substance use and sexual practice s. RESULTS Relative to the comparison group , both the cognitive-behavioral and social support group therapies produced reductions in depression , hostility , and somatization . The social support intervention also produced reductions in overall psychiatric symptoms and tended to reduce maladaptive interpersonal sensitivity , anxiety , and frequency of unprotected receptive anal intercourse , while the cognitive-behavioral intervention result ed in less frequent illicit drug use during the follow-up period . Tests for clinical significance of change particularly underscored benefits of the social support group intervention both at postintervention and at long-term follow-up . CONCLUSIONS Brief group therapy for depressed persons with HIV infection produced reductions in symptoms of distress . The two forms of therapy result ed in shared and unique improvements in functioning , although social support groups focused on emotional coping presented greater evidence of clinical ly significant change . As more persons contract HIV infection and live longer with HIV disease , further research is needed to evaluate outcomes of mental health services with these individuals This study evaluated the magnitude and distribution of unrecognized HIV infection among young men who have sex with men ( MSM ) and of those with unrecognized infection , the prevalence and correlates of unprotected anal intercourse ( UAI ) , perceived low risk for infection , and delayed HIV testing . MSM aged 15 - 29 years were approached , interviewed , counseled , and tested for HIV at 263 r and omly sample d venues in 6 US cities from 1994 - 2000 . Of 5649 MSM participants , 573 ( 10 % ) tested positive for HIV . Of these , 91 % of black , 69 % of Hispanic , and 60 % of white MSM ( 77 % overall ) were unaware of their infection . The 439 MSM with unrecognized infection reported a total of 2253 male sex partners in the previous 6 months ; 51 % had UAI ; 59 % perceived that they were at low risk for being infected ; and 55 % had not tested in the previous year . The HIV epidemic among MSM in the United States continues unabated , in part , because many young HIV-infected MSM are unaware of their infection and unknowingly expose their partners to HIV . To advance HIV prevention in the third decade of HIV/AIDS , prevention programs must reduce unrecognized infection among young MSM by increasing the dem and for and availability of HIV testing services BACKGROUND Methamphetamine-dependent gay and bisexual men ( GBM ) are at high risk for HIV transmission , largely due to drug-associated sexual risk behaviors . This project evaluated the efficacy of four behavioral drug abuse treatments for reducing methamphetamine use and sexual risk behaviors among this population . METHODS In this r and omized controlled trial , 162 methamphetamine-dependent ( SCID-verified ) GBM in Los Angeles County were r and omly assigned to one of four treatment conditions for 16 weeks : st and ard cognitive behavioral therapy ( CBT , n=40 ) , contingency management ( CM , n=42 ) , combined cognitive behavioral therapy and contingency management ( CBT+CM , n=40 ) , and a culturally tailored cognitive behavioral therapy ( GCBT , n=40 ) . Stimulant use was assessed thrice-weekly during treatment using urine drug screens ( 48 measures ) . Sexual risk behaviors were monitored monthly ( four measures ) . Follow-up assessment s were conducted at 6 ( 80.0 % ) and 12 months ( 79.9 % ) . RESULTS Statistically significant differences in retention ( F(3,158)=3.78 , p<.02 ) , in longest period of consecutive urine sample s negative for methamphetamine metabolites ( F(3,158)=11.80 , p<.001 ) , and in the Treatment Effectiveness Score were observed by condition during treatment ( F(3,158)=7.35 , p<.001 ) with post hoc analyses showing the CM and CBT+CM conditions to perform better than st and ard CBT . GEE modeling results showed GCBT significantly reduced unprotected receptive anal intercourse ( URAI ) during the first 4 weeks of treatment ( X2=6.75 , p<.01 ) . During treatment between-group differences disappeared at follow-up with overall reductions in outcomes sustained to 1-year . CONCLUSIONS Among high-risk methamphetamine-dependent GBM , drug abuse treatments produced significant reductions in methamphetamine use and sexual risk behaviors . Drug abuse treatments merit consideration as a primary HIV prevention strategy for this population This study evaluates two AIDS risk-reduction interventions targeted at homosexual and bisexual men . Participants were r and omized into two peer-led interventions : both involved a lecture on ' safer sex ' , and one provided a skills-training component during which men could discuss and rehearse the negotiation of safer sexual encounters . Follow-up data collection assessed self-reported changes in sexual behavior at 6 and 12 months . Skills training increased condom use for insertive anal intercourse . In sessions providing skills training , condom use increased , on average , by 44 % between pre-test and second follow-up compared with only 11 % on average in sessions which did not provide such training Objective To provide the first data which evaluates an HIV risk reduction intervention design ed to reduce HIV high-risk sexual behavior in African-American homosexual and bisexual men . Subjects Participants ( n = 318 ) were recruited from bars , bathhouses , and erotic bookstores , and through homosexual African-American organizations , street outreach , media advertisements , and personal referrals of individuals aware of the study . Methods Participants were r and omized into a single or triple session experimental group or a wait-list control group . Both experimental interventions included AIDS risk education , cognitive-behavioral self-management training , assertion training , and attempts to develop self-identity and social support . Data collection involved assessment s of self-reported changes in sexual behavior at 12− and 18-month follow-up . Results Participants in the triple session intervention greatly reduced their frequency of unprotected anal intercourse ( from 46 to 20 % ) at the 12-month follow-up evaluation and ( from 45 % to 20 % ) at the 18-month follow-up evaluation . However , levels of risky behavior for the control group remained constant ( from 26 to 23 % and from 24 to 18 % ) at 12− and 18-month follow-up evaluations , respectively . In addition , levels of risky behavior for the single session intervention decreased only slightly ( from 47 to 38 % and from 50 to 38 % ) at the 12− and 18-month follow-up evaluations , respectively . Conclusions Results were interpreted to demonstrate the superiority of a triple session over a single session intervention in reducing risky sexual behavior in this cohort |
10,305 | 26,856,938 | Pharmacological and psychological treatments for depression were effective in reducing depressive symptoms in MS .
The data are insufficient to determine the effectiveness of treatments for anxiety | BACKGROUND Depression and anxiety are common in persons with multiple sclerosis ( MS ) , and adversely affect fatigue , medication adherence , and quality of life .
Though effective treatments for depression and anxiety exist in the general population , their applicability in the MS population has not been definitively established .
OBJECTIVE To determine the overall effect of psychological and pharmacological treatments for depression or anxiety in persons with MS . | OBJECTIVES No longitudinal studies have concurrently evaluated predictors of anxiety , depression , and fatigue in people with multiple sclerosis ( PwMS ) . This study determined factors that best predicted anxiety , depression , and fatigue in MS patients from a large pool of disease , cognitive , life-event stressor ( LES ) , psychosocial , life-style , and demographic factors . DESIGN A 2-year prospect i ve longitudinal study evaluated predictors of psychological distress and fatigue in PwMS . METHODS One hundred and one consecutive participants with MS were recruited from two MS clinics in Sydney , Australia . LES , anxiety , depression , and fatigue were assessed at baseline and at 3-monthly intervals for 2-years . Disease , cognitive , demographic , psychosocial , and life-style factors were assessed at baseline . Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria . RESULTS Depression strongly predicted anxiety and fatigue , and anxiety and fatigue strongly predicted later depression . Psychological distress ( i.e. anxiety , depression ) was also predicted by a combination of unhealthy behaviours ( e.g. drug use , smoking , no exercise , or relaxation ) and psychological factors ( e.g. low optimism , avoidance coping ) , similar to the results of community-based studies . However , state-anxiety and fatigue were also predicted by immunotherapy status , and fatigue was also predicted by LES and demographics . CONCLUSIONS These results suggest that similar factors might underpin psychological distress and fatigue in MS patients and community-well sample s , although MS treatment factors may also be important . These results might assist clinicians in determining which MS patients are at greatest risk of developing anxiety , depression , or fatigue OBJECTIVE The aim of this study was to design a trial that could evaluate the effect of acceptance and commitment therapy as a group-intervention for multiple sclerosis patients with psychological distress . DESIGN R and omized controlled trial with assessment at pretreatment , end of treatment , and at 3-month follow-up . SUBJECTS Multiple sclerosis out patients with elevated symptoms of anxiety and /or depression ( n = 21 ) . METHODS Patients were r and omly assigned to acceptance and commitment therapy or relaxation training . Both treatments consisted of 5 sessions over 15 weeks containing didactic sessions , group discussion s , and exercises . Outcome was assessed by self-rated symptoms of anxiety , depression , and a measure of acceptance . RESULTS At 3-month follow-up , the relaxation training group had a significant decline in anxiety symptoms whereas the acceptance and commitment therapy group showed a maintained improvement in rated acceptance at follow-up . CONCLUSION The results reflect the different emphases of the therapies . Acceptance and commitment therapy is aim ed at living an active , valued life and increasing acceptance , while relaxation training focuses directly on coping strategies to h and le emotional symptoms . The results are preliminary , but supportive of further study of brief group interventions for reducing psychological distress in patients with multiple sclerosis 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 Disability status , depression and anxiety are important determinants of quality of life ( Q oL ) in patients with multiple sclerosis ( MS ) . We investigated whether anxiety and depression influence the relation between disability status and Q oL in our cohort of recently diagnosed patients . Disability status [ Exp and ed Disability Status Scale ( EDSS ) ] , anxiety and depression [ Hospital A nxiety and Depression Scale ( HADS ) ] , and Q oL ( SF-36 ) were prospect ively obtained in 101 MS patients . The relation between EDSS and SF-36 scales was examined using regression analyses , without and with adjustment for anxiety and depression . Interaction effects were investigated by comparing the relation between EDSS and Q oL in patients with high and low anxiety and depression . In the unadjusted analyses , EDSS was significantly related to all SF-36 physical and mental health scales . A fter adjustment for anxiety and depression , EDSS was significantly related only to the SF-36 physical functioning , role-physical functioning and bodily pain scales . The relation between EDSS and these SF-36 scales was consistently higher in patients with more symptoms of anxiety or depression , suggesting that anxiety and depression strengthened the association of EDSS in these SF-36 physical health scales . A fter adjustment for anxiety and depression , EDSS was not significantly related to the SF-36 mental health scales and the general health scale . This finding is compatible with the hypothesis that anxiety and depression are intermediate factors in the association of EDSS with these SF-36 scales . Screening for symptoms of anxiety and depression is recommended in studies that use Q oL as an outcome measure of treatment or intervention efficacy Objective : To evaluate the cost effectiveness of a psychological adjustment group shown to be clinical ly effective in comparison with usual care for people with multiple sclerosis . Design : R and omized controlled trial with comparison of costs and calculation of incremental cost effectiveness ratio . Setting : Community . Participants : People with multiple sclerosis were screened on the General Health Question naire 12 and Hospital Anxiety and Depression Scale , and those with low mood were recruited . Interventions : Participants r and omly allocated to the adjustment group received six group treatment sessions . The control group received usual care , which did not include psychological interventions . Main measures : Outcomes were assessed four and eight months after r and omization , blind to group allocation . The costs were assessed from a service use question naire and information provided on medication . Quality of life was assessed using the EQ-5D . Results : Of the 311 patients identified , 221 ( 71 % ) met the criteria for having low mood . Of these , 72 were r and omly allocated to receive treatment and 79 to usual care . Over eight months follow-up there was a decrease in the combined average costs of £ 378 per intervention respondent and an increase in the costs of £ 297 per patient in the control group , which was a significant difference ( p=0.03 ) . The incremental cost-effectiveness ratio indicated that the cost per point reduction on the Beck depression inventory – II was £ 118 . Conclusion : In the short term , the adjustment group programme was cost effective when compared with usual care , for people with multiple sclerosis presenting with low mood . The longer-term costs need to be assessed Anxiety and phobia frequently prevent patients with multiple sclerosis ( MS ) from self-injecting their injectable disease-modifying medications . This small , r and omized , controlled trial tested the efficacy of a six-session nurse-administered programme to teach self-injection to patients with MS , who , due to anxiety or phobia , were unable to self-inject their injectable medications . Participants were 30 patients with MS who were prescribed interferon beta-1a ( IFNβ-1a ) administered via weekly intramuscular injection . All patients were unable to self-inject due to anxiety or phobia . Patients were r and omized to either the six-session Self-Injection Anxiety Therapy ( SIAT ) or a control telephone support condition modelled on the support programme offered by the manufacturer of IFNβ-1a . Four patients dropped out of SIATwhile three dropped out of the control condition . Eight patients receiving SIAT , compared to three control patients , were able to self-inject after six weeks of treatment . SIAT patients were significantly more likely to achieve self-injection at treatment cessation , compared to telephone control patients , in completer analyses ( p=0.022 ) , however , this only reached a trend in intent-to-treat analyses ( p=0.058 ) . These findings suggest that SIAT is a potentially valuable intervention to teach self-injection skills to injection phobic and anxious patients , and should be investigated more thoroughly in a larger clinical trial Objective : There has long been a belief that depression contributes to fatigue in multiple sclerosis ( MS ) although supporting data are minimal at best . Clinical guidelines for the treatment of fatigue include recommendations for the treatment of depression in the absence of clear empirical support . The goal of this study was to examine the effects of treatment for depression on fatigue in MS . Methods : Sixty patients with a relapsing form of MS and moderate to severe depression were r and omly assigned to one of three vali date d 16‐week treatments for depression : individual cognitive behavioral therapy , group psychotherapy , or sertraline . Assessment s at baseline and treatment cessation included the primary outcome measure , fatigue assessment instrument ( FAI ) , and Beck depression inventory ( BDI ) . Results : The total FAI and the global fatigue severity subscale were significantly reduced over the course of treatment ( p values < .02 ) . Other subscales did not change significantly . Secondary analyses showed change in global fatigue severity was associated with change in BDI ( p = .03 ) but change in total FAI was only marginally related to change in BDI ( p = .05 ) . These relationships were due entirely to change in mood ( p values < .02 ) and not to change in cognitive or vegetative symptoms ( p values > .17 ) . Conclusions : These findings suggest that treatment for depression is associated with reductions in the severity of fatigue symptoms , and that this relationship is due primarily to treatment related changes in mood Background People with multiple sclerosis ( MS ) are at high risk of depression . We undertook a pilot trial of computerised cognitive behavioural therapy ( CCBT ) for the treatment of depression in people with MS to test the feasibility of undertaking a full trial . Methods Participants with a diagnosis of MS and clinical levels of depression were recruited through out-patient clinics and postal screening question naires at two UK centres and r and omised to CCBT or usual care . Clinical outcomes included the Beck Depression Inventory ( BDI-II ) and Multiple Sclerosis Impact Scale ( MSIS-29 ) at baseline , 8 and 21 weeks . Feasibility outcomes included : recruitment rate ; reasons for refusal , withdrawal and dropout ; feasibility and acceptability of the proposed outcome measures ; sample size estimation and variation in and preferences for service delivery . Results Twenty-four participants were recruited . The recruitment rate , calculated as the proportion of those invited to fill in a screening question naire who were consented into the trial , was 4.1 % . Recruitment through out-patient clinics was somewhat slower than through screening question naire mail-out but the overall recruitment yield was similar . Of the 12 patients in the CCBT arm , 9 ( 75 % ) completed at least four , and 6 completed all 8 CCBT sessions . For completers , the median time ( IQR ) to complete all eight CCBT sessions was 15 ( 13 to 20 ) weeks . Participants expressed concern about the face validity of the Beck Depression Inventory II for the measurement of self-reported depression in people with MS . The MSIS-29 was the patient-reported outcome measure which participants felt best reflected their concerns . The estimated sample size for a full trial is between 180 and 390 participants . NHS partners were not delivering CCBT in community facilities and participants preferred to access CCBT at home , with no one expressing a preference for use of CCBT in an alternative location . Conclusions A definitive trial , with a recruitment window of one year , would require the participation of around 13 MS centres . This number of centres could be reduced by exp and ing the eligibility criteria to include either other neurological conditions or people with more severe depression . The MSIS-29 should be used as a patient-important outcome measurement . Trial registration IS RCT N : IS RCT In a double-blind clinical trial involving 28 patients with multiple sclerosis and major depressive disorder , 14 patients were r and omly assigned to a 5-week trial of desipramine and individual psychotherapy and 14 to placebo plus psychotherapy . Clinical judgments indicated that patients treated with desipramine improved significantly more than the placebo group . This was confirmed by scores on the Hamilton Rating Scale for Depression but not by Beck Depression Inventory scores . Side effects limited desipramine dosage in half of the treated patients . The authors conclude that desipramine has a modest beneficial effect in serious depression associated with multiple sclerosis but that side effects may be more of a limiting factor than in patients without medical or neurologic disease BACKGROUND Several studies have shown that telephone-administered cognitive-behavioral therapy ( T-CBT ) is superior to forms of no treatment controls . No study has examined if the skills-training component to T-CBT provides any benefit beyond that provided by nonspecific factors . OBJECTIVE To test the efficacy of a 16-week T-CBT against a strong control for attention and nonspecific therapy effects . DESIGN R and omized controlled trial including 12-month follow-up . SETTING Telephone administration of psychotherapy with patients in their homes . PARTICIPANTS Participants had depression and functional impairments due to multiple sclerosis . INTERVENTIONS A 16-week T-CBT program was compared with 16 weeks of telephone-administered supportive emotion-focused therapy . MAIN OUTCOME MEASURES Hamilton Depression Rating Scale score , Structured Clinical Interview for DSM-IV diagnosis of major depressive disorder , Beck Depression Inventory score , and Positive Affect scale score of the Positive and Negative Affect Scale . RESULTS Of the 127 participants r and omized , 7 ( 5.5 % ) dropped out of treatment . There were significant improvement during treatment on all outcome measures ( P<.01 for all ) and an increase in Positive Affect Scale score . Improvements over 16 weeks of treatment were significantly greater for T-CBT , compared with telephone-administered supportive emotion-focused therapy , for major depressive disorder frequency ( P = .02 ) , Hamilton Depression Rating Scale score ( P = .02 ) , and Positive Affect Scale score ( P = .008 ) , but not for the Beck Depression Inventory score ( P = .29 ) . Treatment gains were maintained during 12-month follow-up ; however , differences across treatments were no longer evident ( P > .16 for all ) . CONCLUSIONS Patients showed significant improvements in depression and positive affect during the 16 weeks of telephone-administered treatment . The specific cognitive-behavioral components of T-CBT produced improvements above and beyond the nonspecific effects of telephone-administered supportive emotion-focused therapy on evaluator-rated measures of depression and self-reported positive affect . Attrition was low This study examined the efficacy of an 8-week telephone-administered cognitive-behavioral therapy ( CBT ) for the treatment of depressive symptomatology in multiple sclerosis ( MS ) patients . The treatment , Coping with MS ( CMS ) , included a patient workbook design ed to structure the treatment , provide visual aids , and help with homework assignments . Thirty-two patients with MS , who scored at least 15 on the Profile of Mood States Depression-Dejection scale , were r and omly assigned to either the telephone CMS or to a usual-care control ( UCC ) condition . Depressive symptomatology decreased significantly in the CMS condition compared with the UCC condition . Furthermore , adherence to interferon beta-1a , a disease-modifying medication for the treatment of MS , was significantly better at the 4-month follow-up among patients who received CMS as compared with those in the UCC condition BACKGROUND Studies have been fairly consistent in finding a relationship between social support and depression . However , little is known about the relationship between depression and social support in the context of treatment for depression . This study examined the effects of treatment for depression on social support among patients with multiple sclerosis ( MS ) . METHOD Sixty-three moderately depressed MS patients received 16 weeks of cognitive behaviour therapy ( CBT ) , supportive expressive group psychotherapy ( SEGP ) or sertraline . Depression was measured using the Beck Depression Inventory and social support was measured using Arizona Social Support Interview Schedule . RESULTS Treatment for depression was associated with significant increases in perceived social support , utilized social support and satisfaction with support , as well as reduction in need for emotional support . There were no significant changes in structural support or need for physical support . There were also no differences in change in social support across treatments . All changes in social support were fully explained by depression . Improvements in utilized social support and satisfaction with social support were fully mediated by improvements in depression . Baseline depression predicted improvements in perceived support and need for emotional support . CONCLUSIONS These findings suggest that improvements in social support among MS patients during treatment for depression can be explained by depression . However , different domains of social support may be differentially sensitive to changes in depression Background : Mood problems affect many people with multiple sclerosis ( MS ) . The aim was to evaluate the effectiveness of a group treatment based on cognitive behavioural principles . Methods : People with MS were screened on the General Health Question naire 12 ( GHQ-12 ) and Hospital Anxiety and Depression Scale ( HAD ) . Those identified with low mood were invited to take part in a r and omized trial comparing the effect of attending an adjustment group with a waiting list control . Patients allocated to the adjustment group received six 2 h group treatment sessions . Outcomes were assessed 4 and 8 months after r and omization , blind to group allocation . Results : Of the 311 patients identified , 221 ( 71 % ) met the criteria for low mood and 151 ( 68 % ) agreed to take part . Hierarchical regression analyses were conducted to compare the two groups , correcting for baseline mood and disability . At 4 months , group allocation alone was a significant predictor of the primary outcome measure , the GHQ-12 . At 8 months , group allocation alone was no longer a significant predictor for GHQ-12 scores , but it was when baseline GHQ-12 and Guy ’s Neurological Disability Scale scores were controlled for . Comparison of the area under the curve revealed significant differences between the groups for GHQ-12 ( p = 0.003 ) , HAD Anxiety ( p = 0.013 ) , HAD Depression ( p = 0.004 ) , Beck Depression Inventory ( p = 0.001 ) , MS Self-efficacy ( p = 0.037 ) and MS Impact Scale Psychological ( p = 0.012 ) . Conclusion : Patients receiving treatment were less distressed and had less depression and anxiety . There was some evidence of improved self-efficacy and a reduction of the impact of MS on people ’s lives The purpose of the study was to evaluate the prevalence of insomnia in multiple sclerosis patients with comorbid depression , associations between psychological symptoms , multiple sclerosis symptoms and insomnia , and to test effects of a 16-week protocol -based psychotherapy intervention for depression on insomnia symptoms . Participants with multiple sclerosis and depression ( n = 127 ) were r and omized to telephone administered cognitive behavioral therapy and telephone administered supportive emotion-focused therapy . Multiple sclerosis functional limitation was measured at baseline . Depression , insomnia , anxiety and quality of life were evaluated at pre treatment , mid treatment ( 8 weeks ) , and post treatment ( 16 weeks ) . Prevalence of insomnia ≥3 times per week was 78 % at pre treatment and 43 % at post treatment . Insomnia at baseline was associated with depression , multiple sclerosis related mood symptoms and anxiety . Middle of the night awakenings were associated with swallowing and speech problems . Improvements in insomnia were associated with improvement in depression and anxiety . Participants with residual insomnia were more likely to have major depressive disorder , greater multiple sclerosis severity , elevated anxiety and lower mental components of quality of life . Results demonstrate rates of insomnia in patients with comorbid multiple sclerosis and depression are higher than those reported in the general multiple sclerosis population and additional insomnia treatment is indicated beyond the treatment of comorbid psychological disorders OBJECTIVE The objective of this study was to evaluate the efficacy of paroxetine in treating major depressive disorder ( MDD ) in persons with multiple sclerosis ( MS ) . METHOD In this double-blind trial , 42 participants with MS and MDD were r and omly assigned to one of two parallel 12-week treatment arms : paroxetine or placebo . The participants started at an initial dose of 10 mg/day paroxetine or placebo , titrated up to 40 mg daily based on symptoms response and side effects . The primary outcome measure was the Hamilton Rating Scale for Depression ( HAM-D ) . Secondary outcomes included fatigue , anxiety and self-reported quality of life . RESULTS Intent-to-treat analyses revealed that both groups improved from pretreatment to posttreatment . Although the treatment group improved more than the control group on most measures , few differences were statistically significant . For the primary outcome , 57.1 % of participants in the treatment arm had at least a 50 % reduction in HAM-D score , compared with 40 % in the control group ( nonsignificant ) . Treatment effects were greater among the participants who completed the study ; 78.6 % of completers had a treatment response compared with 42.1 % of controls ( P=.073 ) . CONCLUSION Although paroxetine may not be efficacious for all persons with MS and MDD , it appears to benefit some individuals The Sonya Slifka Longitudinal Multiple Sclerosis Study follows a population -based cohort of approximately 2000 people with multiple sclerosis ( MS ) to study demographic and clinical characteristics , course of illness , utilization and cost of health services , provider characteristics , use of MS specialists and disease modifying agents , and neurologic , economic and psychosocial outcomes . This report describes the study methodology , presents baseline demographic and clinical data , and evaluates the representativeness of the sample . A stratified r and om sample of persons with established and recently-diagnosed MS selected from the National Multiple Sclerosis Society ( NMSS ) mailing lists was supplemented with recently-diagnosed patients recruited through systematic nationwide outreach . Baseline data were collected by computer-assisted telephone interviews derived from st and ardized instruments ; data collection continues at six-month intervals . The cohort was comparable to population -based and clinical sample s with respect to demographics , course , relapse rate , symptoms , and severity of disability . Almost two-thirds of the cohort needed help with activities of daily living , three-quarters were limited in work or other activities , and half had emotional problems that compromised quality of life . The Slifka Study cohort is broadly representative of the MS population and the data base can be used to address questions not answered by natural history studies , clinical data bases , or population -based surveys Objective : The aim was to evaluate a group treatment for people with multiple sclerosis and low mood . Design : R and omized controlled trial . Setting : Community . Participants : Patients with multiple sclerosis and low mood , scoring > 7 on the Hospital Anxiety and Depression Scales or > 2 on the General Health Question naire 12 . Interventions : Participants either attended an adjustment group for six , 2-hour group treatment sessions or were on a waiting list to attend the group . Outcomes : Hospital Anxiety and Depression Scale , General Health Question naire 12 , Multiple Sclerosis Self Efficacy Scale , Multiple Sclerosis Impact Scale and Short Form 36 administered 3 and 6 months after r and om allocation . Results : Of the 219 patients identified , 100 ( 46 % ) reported depressive symptoms and 126 ( 58 % ) anxiety symptoms . Forty participants were recruited , aged 25—68 ( mean 47.7 SD 9.7 ) and eight were men . Patients allocated to the group intervention reported fewer depressive symptoms than those in the control group ( U 109.5 , P<0.05 ) but there were no significant differences in anxiety symptoms , self-efficacy or quality of life . Conclusion : Depressive symptoms were reduced following group intervention , which suggests this may be an effective psychological treatment and warrants further evaluation OBJECTIVE Previous analyses showed that a telephone-based intervention to increase physical activity in individuals with multiple sclerosis ( MS ) and depression result ed in significantly improved depressive symptoms compared to a wait-list control group . The aim of this study was to test positive affect and negative affect as mediators of the effect of the physical activity counseling on depressive symptoms . METHOD Ninety-two adults with MS , who met diagnostic criteria for either major depression or dysthymia and who reported low levels of physical activity , were r and omized 1:1 to a 12-week telephone-based motivational interviewing ( MI ) intervention to improve physical activity ( n = 44 ) or to a 12-week wait-list control group ( n = 48 ) . Self-reported positive and negative affect , physical activity , and depressive symptoms were gathered at baseline and postintervention . Path- analysis was used to test whether positive affect and negative affect mediated the positive effects of the intervention on depressive symptoms . RESULTS Both positive and negative affect were significant mediators of the effects of the intervention on depressive symptoms ; however , only positive affect mediated the association between changes in physical activity and improved depressive symptoms . CONCLUSIONS Findings support physical activity and positive affect as key mediators of the MI treatment effect on improved mood . Decreases in negative affect were also evident in the treatment group , but were not related to improved physical activity . Findings may suggest the use of exercise-based interventions in conjunction with treatments that specifically target negative affective mechanisms for depression The present study examined the relationship between therapeutic alliance and both depression and health outcomes in a r and omized clinical trial of 2 telephone-administered treatments with 97 clients with multiple sclerosis ( MS ) . The 16-week , manualized treatments compared were telephone-administered cognitive-behavioral therapy ( T-CBT ) and telephone-administered supportive emotion focused therapy ( T-SEFT ) , an experiential treatment . Alliance scores were significantly higher in T-CBT compared with T-SEFT , and treatment moderated the relationship between alliance and outcome on some of the measures . Specifically , alliance predicted subsequent improvements in depression within the T-CBT condition , but not in T-SEFT , controlling for early symptom change . The authors found a similar trend for alliance and MS-related disability in T-CBT only . This is one of the first studies to examine the role of alliance in outcome for the emerging modality of telephone therapy and one of the few to relate alliance to health outcomes . The findings suggest that the therapist-client relationship is important to improvement in telephone therapy and that the role of alliance in outcome may vary by treatment approach This study examined the effects of brain lesions and neuropsychological impairment on the efficacy of treatment for depression in patients with comorbid diagnoses of multiple sclerosis ( MS ) and major depressive disorder ( MDD ) . Thirty patients meeting criteria for MS and MDD received 1 of 3 16-week treatments for depression and were followed for 6 months following treatment cessation . T2-weighted magnetic resonance imaging and neuropsychological evaluations were also obtained . End-of-treatment Beck Depression Inventory ( BDI ; A. T. Beck , C. H. Ward , M. Mendelson , J. Mock , & J. Erbaugh , 1961 ) results residualized for baseline BDI were related to right temporal periventricular lesion volume ( R2=.32 , p=.002 ) and left temporal grey-white junction lesion volume ( R2=.19 , p=.02 ) but were not statistically related to lesion volume in any other brain region or to neuropsychological function . BDI results at 6-month follow-up , residualized for end-of-treatment BDI , were predicted by total lesion volume ( R2=.22 , p=.005 ) , lesion volume in many discrete areas , and neuropsychological functioning ( R2=.29 , p=.0009 ) . The effect of total lesion volume on 6-month follow-up BDI results was fully mediated by neuropsychological function OBJECTIVE To examine the relationship between depression , treatment of depression , and interferon gamma ( IFN-gamma ) production by peripheral blood mononuclear cells in patients with comorbid diagnoses of relapsing-remitting multiple sclerosis ( MS ) and major depressive disorder . DESIGN A r and omized comparative outcome trial of three 16-week treatments for depression . Assessment s were conducted at baseline , week 8 , and treatment cessation . SETTING An academic outpatient treatment and clinical research center . PATIENTS Fourteen patients who met the criteria for relapsing-remitting MS and major depressive disorder . INTERVENTIONS Individual cognitive behavioral therapy , group psychotherapy , or sertraline therapy . MAIN OUTCOME MEASURES Depression was assessed using the Beck Depression Inventory . Interferon gamma production by peripheral blood mononuclear cells was measured following stimulation with OKT3 or recombinant human myelin oligodendrocyte glycoprotein ( MOG ) . Variability in immune assays was controlled using 8 nondepressed healthy subjects who were enrolled at times corresponding with the enrollment of MS patients . RESULTS Results of the Beck Depression Inventory were significantly related to IFN-gamma production stimulated with OKT3 or MOG at baseline ( P < or = .03 for all ) . Level of depression , OKT3-stimulated IFN-gamma production , and MOG-stimulated IFN-gamma production all declined significantly over the 16-week treatment period ( P < or = .03 for all ) . Among controls , there were no significant changes over time in OKT3- or MOG-stimulated IFN-gamma , or in depression ( P > or = .25 for all ) . CONCLUSIONS These findings suggest that the production of the proinflammatory cytokine IFN-gamma by autoaggressive T cells in relapsing-remitting MS is related to depression and that treatment of depression may decrease IFN-gamma production . Thus , treatment of depression may provide a novel disease-modifying therapeutic strategy as well as a symptomatic treatment for patients with MS This study compared the efficacy of 3 16-week treatments for depression in 63 patients with multiple sclerosis ( MS ) and major depressive disorder ( MDD ) : individual cognitive-behavioral therapy ( CBT ) , supportive-expressive group therapy ( SEG ) . and the antidepressant sertraline . Significant reductions were seen from pre- to posttreatment in all measures of depression . Intent-to-treat and completers analyses using the Beck Depression Inventory ( BDI ; A. T. Beck , C. H. Ward . M. Medelson . J. Mock , & J. Erbaugh , 1961 ) and MDD diagnosis found that CBT and sertraline were more effective than SEG at reducing depression . These results were largely supported by the BDI-18 , which eliminates BDI items confounded with MS . However , the Hamilton Rating Scale for Depression ( M. Hamilton , 1960 ) did not show consistent differences between treatments . Reasons for this inconsistency are discussed . These findings suggest that CBT or sertraline is more likely to be effective in treating MDD in MS compared with supportive group treatments OBJECTIVE This study examined the buffering effects of social support on the relationship between depression and autoaggressive immune function in multiple sclerosis ( MS ) . METHODS Fourteen participants with comorbid diagnoses of MS and major depressive disorder received 16 weeks of psychotherapy or antidepressant medications . Depression and T-cell production of interferon-gamma ( IFN-gamma ) , a lynchpin in MS pathogenesis , were assessed at baseline and posttreatment . Social support was assessed at baseline . RESULTS Both depression and T-cell production of IFN-gamma were significantly reduced over the 16 weeks of treatment . There was a significant interaction between change in depression , change in IFN-gamma , and social support ( R(2)=.26 , P=.03 ) such that social support served as a buffer . CONCLUSION These results support the hypothesis that social support buffers the effects of change in depression on IFN-gamma production . However , these findings should be viewed as preliminary due to the small sample size and the absence of a control condition OBJECTIVE Physical activity represents a promising treatment for major depressive disorder ( MDD ) in people with multiple sclerosis ( MS ) . We conducted a single-blind , two-arm r and omized controlled trial comparing a 12-week physical activity counseling intervention delivered primarily by telephone ( n = 44 ) to a wait-list control group ( N = 48 ) . METHOD Ninety-two adults with MS and MDD or dysthymia ( M(age ) = 48 years ; 86 % female , 92 % White ) completed an in-person baseline assessment and were r and omized to wait-list control or an intervention involving motivational-interviewing-based promotion of physical activity . The treatment group received an initial in-person session ; 7 telephone counseling sessions ( Weeks 1 , 2 , 3 , 4 , 6 , 8 , and 10 ) , and an in-person session at Week 12 . The primary outcome , treatment response , was defined as those with 50 % or greater reduction in the Hamilton Depression Rating Scale ( HAM-D ) score . RESULTS Our primary hypothesis , that the proportion of responders in the treatment group would be significantly greater than in the control group , was not confirmed . However , compared with the control group , those in the treatment group evidence d significantly lower depression severity on the HAM-D , on self-reported depression , and on a measure of potential side effects and at 12 weeks were less likely to meet the criteria for MDD as set forth in the Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ) . Physical activity increased significantly more in the treatment condition , though it did not mediate improvement in depression severity . CONCLUSIONS Telephone-based physical activity promotion represents a promising approach to treating MDD in MS . Further research is warranted on ways to bolster the impact of the intervention and on mediators of the treatment effect Twenty depressed multiple sclerotic patients were r and omly allocated either to cognitive-behaviour therapy or to a waiting list control condition . Assessment of depressive symptoms was conducted at pre-treatment , post-treatment , and a four-week follow-up . In comparison to the waiting list condition , cognitive-behaviour therapy was found to result in clinical ly and statistically significant improvement on most measures . Although the mechanism by which such treatment achieves its effects is unclear , these results clearly support the use of cognitive-behavioural treatments for depression in this population IMPORTANCE Many medications have anticholinergic effects . In general , anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy . However , a few studies suggest that anticholinergics may be associated with an increased risk for dementia . OBJECTIVE To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve population -based cohort study using data from the Adult Changes in Thought study in Group Health , an integrated health care delivery system in Seattle , Washington . We included 3434 participants 65 years or older with no dementia at study entry . Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003 . Beginning in 2004 , continuous replacement for deaths occurred . All participants were followed up every 2 years . Data through September 30 , 2012 , were included in these analyses . EXPOSURES Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure , which was defined as the total st and ardized daily doses ( TSDDs ) dispensed in the past 10 years . The most recent 12 months of use was excluded to avoid use related to prodromal symptoms . Cumulative exposure was up date d as participants were followed up over time . MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer disease using st and ard diagnostic criteria . Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics , health behaviors , and health status , including comorbidities . RESULTS The most common anticholinergic classes used were tricyclic antidepressants , first-generation antihistamines , and bladder antimuscarinics . During a mean follow-up of 7.3 years , 797 participants ( 23.2 % ) developed dementia ( 637 of these [ 79.9 % ] developed Alzheimer disease ) . A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease ( test for trend , P < .001 ) . For dementia , adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 ( 95 % CI , 0.74 - 1.16 ) for TSDDs of 1 to 90 ; 1.19 ( 95 % CI , 0.94 - 1.51 ) for TSDDs of 91 to 365 ; 1.23 ( 95 % CI , 0.94 - 1.62 ) for TSDDs of 366 to 1095 ; and 1.54 ( 95 % CI , 1.21 - 1.96 ) for TSDDs greater than 1095 . A similar pattern of results was noted for Alzheimer disease . Results were robust in secondary , sensitivity , and post hoc analyses . CONCLUSIONS AND RELEVANCE Higher cumulative anticholinergic use is associated with an increased risk for dementia . Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time |
10,306 | 20,693,253 | EBUS is a safe and relatively accurate tool in the investigation of PPLs .
Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size . | Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions ( PPLs ) with the use of radial probe endobroncial ultrasound ( EBUS ) has been reported , although diagnostic performance varies considerably . | STUDY OBJECTIVE To evaluate the feasibility of lung cancer screening using low-dose spiral CT as a part of annual health examinations . DESIGN Nonr and omized , screening practice . METHODS From April 1998 to August 2000 , CT screening was performed as a part of annual health examinations on a total of 7,956 individuals who belonged to the Hitachi Employee 's Health Insurance Group . Of those participants , 5,568 were rescreened 1 year later . When a noncalcified solitary pulmonary nodule ( SPN ) > or= 8 mm was detected on CT screening , a detailed CT scan was carried out approximately 1 month later . RESULTS During the baseline screening , a total of 2,865 noncalcified SPNs were detected among the 7,956 participants . Primary lung cancer was histologically confirmed in 40 patients ( 41 lesions ) . The prevalence was 0.44 % of all participants from the baseline , and 0.07 % from the repeated screening . Thirty-five of 41 tumors were stage I. Current or former smokers represented only 17 of 40 cases . The detection rate was rather high in female participants . CONCLUSION Low-dose spiral CT seems to be a promising method for screening early lung cancer as a part of annual health examinations . Female and nonsmoking subjects should be included in the baseline screening . However , for yearly repeat screening , the participants may be selected on the basis of gender , smoking history , and results at the baseline screening STUDY OBJECTIVE To assess the ability of endobronchial ultrasonography ( EBUS ) using a guide sheath ( EBUS-GS ) to diagnose peripheral pulmonary lesions . METHOD We devised a technique for EBUS-GS covering a miniature probe , and 150 lesions were evaluated in a prospect i ve open study . In this procedure , the probe covered by a guide sheath is introduced into the lesion via the working channel of a bronchoscope . The probe is withdrawn , while the guide sheath is left in situ . A brush or biopsy forceps is introduced through the guide sheath into the lesion . RESULTS One hundred sixteen of 150 EBUS-GS procedures ( 77 % ) were diagnostic . Cases in which the probe was located within the lesion had a significantly higher diagnostic yield ( 105 of 121 cases , 87 % ) than when the probe was located adjacent to it ( 8 of 19 cases , 42 % ) [ p < 0.0001 , chi(2 ) ] . The diagnostic yield from EBUS-GS in lesions < /= 10 mm ( 16 of 21 lesions , 76 % ) , > 10 to < /= 15 mm ( 19 of 25 lesions , 76 % ; p = 0.99 , chi(2 ) ) , > 15 to < /= 20 mm ( 23 of 35 lesions , 66 % ; p = 0.41 , chi(2 ) ) , and > 20 to < /= 30 mm ( 33 of 43 lesions , 77 % ; p = 0.96 , chi(2 ) ) were similar , demonstrating the efficacy of EBUS-GS even in lesions < /= 10 mm in diameter . In 54 of 81 lesions < /= 20 mm , fluoroscopy was not able to confirm whether the forceps reached the lesion . However , the yield was the same with ( 67 % , 18 of 27 lesions ) and without ( 74 % , 40 of 54 lesions ) successful fluoroscopy ( p = 0.96 , chi(2 ) ) . Moderate bleeding occurred in two patients ( 1 % ) ; there were no other complications . CONCLUSIONS EBUS-GS is a useful method for collecting sample s from peripheral pulmonary lesions , even those too small to be visualized under fluoroscopy PURPOSE To report results of a 5-year prospect i ve low-dose helical chest computed tomographic ( CT ) study of a cohort at high risk for lung cancer . MATERIAL S AND METHODS After informed written consent was obtained , 1520 individuals were enrolled . Protocol was approved by institutional review board and National Cancer Institute and was compliant with Health Insurance Portability and Accountability Act , or HIPAA . Participants were aged 50 years and older and had smoked for more than 20 pack-years . Participants underwent five annual ( one initial and four subsequent ) CT examinations . A significant downward shift was evaluated in non-small cell lung cancers detected initially from advanced stage down to stage I by using a one-sided binomial test of proportions . Poisson regression and Fisher exact tests were used for comparisons with Mayo Lung Project . RESULTS In 788 ( 52 % ) men and 732 ( 48 % ) women , 61 % ( 927 of 1520 ) were current smokers , and 39 % were former smokers . After five annual CT examinations , 3356 uncalcified lung nodules were identified in 1118 ( 74 % ) participants . Sixty-eight lung cancers were diagnosed ( 31 initial , 34 subsequent , three interval cancers ) in 66 participants . Twenty-eight subsequent cases of non-small cell cancers were detected , of which 17 ( 61 % ; 95 % confidence interval : 41 % , 79 % ) were stage I tumors . Diameter of cancers detected subsequently was 5 - 50 mm ( mean , 14.4 mm ; median , 10.0 mm ) . Analysis for a more than 50 % shift in proportion of stage I non-small cell cancer detection did not show statistical significance . Forty-eight participants died of various causes since enrollment . Lung cancer mortality rate for incidence portion of trial was 1.6 per 1000 person-years . There was no significant difference in lung cancer mortality rates of cancers detected in subsequent examinations between this trial and Mayo Lung Project after separation of participants into subsets ( 2.8 vs 2.0 per 1000 person-years , P = .43 ) . CONCLUSION CT allows detection of early-stage lung cancers . Benign nodule detection rate is high . Results suggest no stage shift To evaluate the individual and additive diagnostic yield(s ) of several bronchoscopic sampling techniques for the diagnosis of lung lesions with no corresponding airway abnormalities , consecutive patients with lung nodules or masses were prospect ively evaluated between December 1989 and November 1994 . A CT of the chest was done in all patients before flexible bronchoscopy ( FB ) . Size , location , and character of the border of the lesion were determined . During FB , using biplane fluoroscopic guidance , the lesion was localized and following sampling techniques were done : brushing , transbronchial lung biopsy ( TBLB ) , and Sofcor transbronchial needle aspiration ( STBNA ) . Bronchial washings ( BWs ) were collected throughout the procedure . Problems associated with each sampling technique were noted . Forty-nine patients underwent 51 FB . A diagnosis was established by FB in 36 ( 73 % ) . After a nondiagnostic FB , histologic diagnosis was established in 9 of 13 patients by other methods . A benign or malignant nature of lesion was established in other four patients by clinical follow-up . FB was diagnostic in 32 of 40 ( 80 % ) patients with primary lung cancer , in 3 of 6 ( 50 % ) patients with benign disease , and in 1 of 3 ( 33 % ) patients with metastatic disease to lung . All sampling procedures could be done in 33 of 51 ( 65 % ) FBs . Overall diagnostic yields were as follows : BW , 18 of 51 ( 35 % ) ; brush , 25 of 48 ( 52 % ) ; TBLB , 23 of 40 ( 57 % ) ; and STBNA , 19 of 37 ( 51 % ) . In 12 of 51 ( 24 % ) FBs , only one sample was diagnostic . Lesions with sharp borders had a lower combined diagnostic yield , 13 of 24 ( 54 % ) compared to lesions with fuzzy borders , 20 of 24 ( 83 % ) ( p=0.03 ) . Yield of TBLB in lesions with fuzzy borders , 14 of 18 ( 78 % ) , was higher than the yield for lesions with sharp borders , 6 of 19 ( 32 % ) ( p=0.005 ) . Size of the lesion in centimeters in patients with a positive FB ( 4.55+/- 2.35 ; mean + /-SD ) was significantly larger than in patients with a nondiagnostic FB ( 3.14+/-1.31 ; mean+/-SD ) ( p=0.009 , t test ) . Diagnostic yield was directly related to the size of the lesion . For lesions less than 2 cm , yield was 6 of 11 ( 54 % ) ( p=0.19 ) ; for lesions less than 3 cm , yield was 12 of 21 ( 57 % ) ( p=0.07 ) ; and for lesions greater than 3 cm , yield was 24 of 30 ( 80 % ) . Yield from lesions located in the lower lobe basal segments or the apical segment of upper lobes was lower ( 11/19 , 58 % ) than that from lesions in other parts of the lung ( 25/30 , 83 % ) ( p=0.05 ) . FB was terminated prior to collecting all sample s because of severe bleeding after brushing ( n=3 ) or instability of the patient ( n=4 ) . None of the patients required intubation . There were no pneumothoraces . Diagnostic yield of FB depends on the location , size , character of the border of the lesion , and the ability to perform all sampling methods . Brushing , TBLB , and STBNA should be performed in all patients to give the best diagnostic yield . Routine cytologic examination of BW is unnecessary . Methods other than FB should be considered for lesions 2 cm or less in size , especially when they have a sharp border and /or are located in the basal segment of a lower lobe/apical segment of an upper lobe BACKGROUND Low-dose spiral CT of the chest effectively detects early-stage lung cancer in high-risk individuals . The high rate of benign nodules and issues of making a differential diagnosis are critical factors that currently hamper introduction of large-scale screening programmes . We investigated the efficacy of repeated yearly spiral CT and selective use of positron emission tomography ( PET ) in a large cohort of high-risk volunteers . METHODS We enrolled 1035 individuals aged 50 years or older who had smoked for 20 pack-years or more . All patients underwent annual low-dose CT , with or without PET , for 5 years . Lesions up to 5 mm were deemed non-suspicious and low-dose CT was repeated after 12 months ( year 2 ) . FINDINGS By year 2 , 22 cases of lung cancer had been diagnosed ( 11 at baseline , 11 at year 2 ) . 440 lung lesions were identified in 298 ( 29 % ) participants , and 95 were recalled for high-resolution contrast CT . PET scans were positive in 18 of 20 of the identified cancer cases . Six patients underwent surgical biopsy for benign disease because of false-positive results ( 6 % of recalls , 22 % of invasive procedures ) . Complete resection was achieved in 21 ( 95 % ) lung cancers , 17 ( 77 % ) were pathological stage I ( 100 % at year 2 ) , and the mean tumour size was 18 mm . There were no interval lung cancers in the 2.5 years of follow-up ( average time on study from r and omisation to last contact ) , although 19 individuals were diagnosed with another form of cancer ( two deaths and 17 non-fatal admissions ) . INTERPRETATION Combined use of low-dose spiral CT and selective PET effectively detects early lung cancer . Lesions up to 5 mm can be checked again at 12 months without major risks of progression STUDY OBJECTIVES We evaluated the feasibility and efficacy of transbronchial biopsy ( TBB ) and bronchial brushing by endobronchial ultrasonography ( EBUS ) with a guide sheath ( GS ) as a guide for diagnosing peripheral pulmonary lesions ( PPLs ) without radiographic fluoroscopy . PATIENTS One hundred twenty-one patients with 123 PPLs ( mean diameter , 31.0 mm ) whose bronchoscopic findings were normal . METHODS An EBUS-GS was inserted and advanced to the PPL without fluoroscopy . Once we obtained the EBUS image , the probe was withdrawn and the GS was left in place . TBB and /or bronchial brushing were performed via the GS . When an EBUS image could not be obtained , we changed to the bronchoscopic examination under fluoroscopy . RESULTS Seventy-six of 123 PPLs ( 61.8 % ) were diagnosed by EBUS-GS guidance without fluoroscopy . The diagnostic yield for PPLs > 20 mm in diameter ( 75.6 % ) was significantly higher than that for those < or= 20 mm in diameter ( 29.7 % ; p < 0.01 ) . The PPLs located in the middle lobe and the lingular segment had significantly higher diagnostic yields ( p < 0.05 ) . When the bronchus leading to the PPL was identified on the CT scan , the yield was 79.2 % . Moreover , the solid lesions had a higher diagnostic yield ( 67.0 % ) compared with nonsolid lesions ( 35.0 % ; p < 0.05 ) . Multivariate analysis revealed that the diameter and the location of the PPL were independent predictors of diagnostic sensitivity by EBUS-GS-guided bronchoscopy ( p < 0.05 ) . CONCLUSIONS EBUS-GS-guided bronchoscopy without the use of radiographic fluoroscopy is effective for diagnosing PPLs . The diameter , location , and CT scan appearance of the PPLs , and the identification of the bronchus leading to the PPLs were valuable as factors related to a higher diagnostic sensitivity with this procedure Endobronchial ultrasonography ( EBUS ) with a radial scanning probe provides cross-sectional images of peripheral pulmonary lesions . We devised a technique of EBUS for the diagnosis of peripheral pulmonary lesions . EBUS using a thick guide sheath ( GS ) [ 2.5 mm in diameter ] covering a miniature probe , and 150 lesions were evaluated in a prospect i ve open study . In the procedure of EBUS-GS , the probe covered by a GS is introduced into the lesion via the working channel of a bronchoscope . The probe is withdrawn , while the GS is left in situ . A brush or biopsy forceps is introduced through the GS into the lesion . EBUS visualized the image in 93 % of the peripheral pulmonary lesions . One hundred sixteen ( 77 % ) of 150 EBUS-GS procedures were diagnostic . Cases in which the probe was located within the lesion , had a significantly higher diagnostic yield ( 105/121 , 87 % ) than when the probe was located adjacent to it ( 8/19 , 42 % ) . Diagnostic yield from EBUS-GS in lesions < or = 10 mm ( 16/21 , 76 % ) , 10 < , < or = 15 mm ( 19/25 , 76 % , p=0.99 , chi2 ) , 15 < , < or = 20 mm ( 24/35 , 69 % , p=0.41 , chi2 ) , and 20 < , < or = 30 mm ( 33/43 , 77 % , p=0.96 , chi2 ) were similar , demonstrating the efficacy of EBUS-GS even in lesions < or = 20 mm in diameter Transbronchial biopsy ( TBBX ) for peripheral lung lesions is usually performed with the help of fluoroscopy , but the yield varies widely . This feasibility study aim ed to assess the ability of endobronchial ultrasound ( EBUS ) to provide imaging guidance for TBBX . In a prospect i ve study , 50 consecutive patients referred for TBBX for peripheral lesions underwent fluoroscopy-guided and EBUS-guided TBBX in r and om order . Diagnostic yields were compared for both modalities and feasibility was assessed for EBUS . Diagnostic material was obtained in 80 % of patients with EBUS and 76 % of patients with fluoroscopy . There was a nonsignificant trend for EBUS to be better than fluoroscopy for lesions <3 cm in diameter . Four lesions could not be visualised with EBUS . There were no significant complications associated with the use of EBUS . Endobronchial ultrasound-guided transbronchial biopsy is feasible . It appears to be at least equivalent to fluoroscopy without the accompanying radiation exposure . Further large-scale studies are indicated to assess the possible role of endobronchial ultrasound as a potential imaging method of choice for the biopsy of peripheral lung lesions BACKGROUND A clinical prediction model to identify malignant nodules based on clinical data and radiological characteristics of lung nodules was derived using logistic regression from a r and om sample of patients ( n = 419 ) and tested on data from a separate group of patients ( n = 210 ) . OBJECTIVE To use multivariate logistic regression to estimate the probability of malignancy in radiologically indeterminate solitary pulmonary nodules ( SPNs ) in a clinical ly relevant subset of patients with SPNs that measured between 4 and 30 mm in diameter . PATIENTS AND METHODS A retrospective cohort study at a multispecialty group practice included 629 patients ( 320 men , 309 women ) with newly discovered ( between January 1 , 1984 , and May 1 , 1986 ) 4- to 30-mm radiologically indeterminate SPNs on chest radiography . Patients with a diagnosis of cancer within 5 years prior to the discovery of the nodule were excluded . Clinical data included age , sex , cigarette-smoking status , and history of extrathoracic malignant neoplasm , asbestos exposure , and chronic interstitial or obstructive lung disease ; chest radiological data included the diameter , location , edge characteristics ( eg , lobulation , spiculation , and shagginess ) , and other characteristics ( eg , cavitation ) of the SPNs . Predictors were identified in a r and om sample of two thirds of the patients and tested in the remaining one third . RESULTS Sixty-five percent of the nodules were benign , 23 % were malignant , and 12 % were indeterminate . Three clinical characteristics ( age , cigarette-smoking status , and history of cancer [ diagnosis , > or = 5 years ago ] ) and 3 radiological characteristics ( diameter , spiculation , and upper lobe location of the SPNs ) were independent predictors of malignancy . The area ( + /-SE ) under the evaluated receiver operating characteristic curve was 0.8328 + /- 0.0226 . CONCLUSION Three clinical and 3 radiographic characteristics predicted the malignancy in radiologically indeterminate SPNs BACKGROUND We assessed the effectiveness of applying the distance from the orifice of the bronchus to visualized peripheral pulmonary lesion ( PPL ) under endobronchial ultrasonography ( EBUS ) to transbronchial biopsy ( TBB ) , as an alternative to EBUS with a guide sheath ( GS ) and fluoroscopy . PATIENTS AND METHODS From October 2004 to July 2005 , a total of 158 consecutive patients with solitary PPLs , which were not visualized under flexible video bronchoscopy , were received EBUS for advanced localization subsequently . One hundred and thirteen of 158 patients with solitary PPLs which were visualized on EBUS image were included in this prospect i ve study and r and omly divided into two groups for TBB using different methods . In group EBUS-D ( 57 patients ) the distance from the bronchial orifice to pulmonary lesion was measured , then the biopsy forceps were advanced to this measured distance and biopsy followed . In group EBUS ( 56 patients ) the biopsy forceps were advanced regardless of distance . The diagnostic yields were then compared . RESULTS TBBs in group EBUS-D patients had a significantly higher diagnostic yield ( 45/57 , 78.9 % ) than group EBUS patients ( 32/56 , 57.1 % ) [ P=0.013 ] . Size and location of lesion , duration of EBUS , diagnosis of malignancy , and whether the probe was located within the lesion on EBUS image did not differ between these two groups . Mild bleeding occurred in three patients in group EBUS-D and two in group EBUS . One group EBUS patient had a self-limited pneumothorax . CONCLUSIONS Measuring and applying the distance between the orifice of bronchus and the lesion could increase the diagnostic yield of EBUS-guided TBBs for PPLs Background and Objective : Conventional imaging procedures proved to be insufficient for staging of lung cancer , especially with respect to N-stage , infiltration of mediastinal structures , and early lung cancer . As also the view of the endoscopist is restricted , we developed the new method of endobronchial ultrasonography ( EBUS ) as an adjunct to conventional bronchoscopy . The initial technical problems were solved by development of a balloon catheter for application of miniaturized 20-MHz probes . Patients and Methods : Between January and December , 1999 all patients with an indication for bronchoscopy and additional EBUS were documented prospect ively . Results : In 648 patients we used additional EBUS . Of these , 242 ( 37 % ) were female and 406 ( 63 % ) were male . The mean age was 49.2 ( range 0–83 ) years . The mean procedure time for the bronchoscopies was 18.9 ( range 5.7–38.9 ) min , and the mean time for EBUS was 6.3 ( range 3.1–14.4 ) min . Side effects were comparatively rare . 34 patients ( 5 % ) needed supplementary oxygen during the examination , the others tolerated EBUS without any desaturation . Conclusion : EBUS is a new technology that can be easily applied and is well tolerated . It improves the results of bronchoscopy in addition to conventional diagnostic procedures . Further developments will be made in future to improve the application of ultrasound in chest medicine BACKGROUND Choice of biopsy method for peripheral lung lesions is usually between CT-guided fine-needle aspiration biopsy ( CT FNA ) and bronchoscopy . Endobronchial ultrasound guide-sheath biopsy ( EBUS GS ) is a new method to improve the yield of bronchoscopy . Guidance on which lesions would be appropriate for either method is needed . The aim of the study was to compare the diagnostic yields and pneumothorax rate of EBUS GS and CT FNA in terms of the location of the lesion needing biopsy , in particular , whether the lesion is touching the pleura . METHODS Prospect i ve series of EBUS GS were compared to retrospective review of CT FNA carried out simultaneously in a large teaching hospital . RESULTS For EBUS GS 140 cases were carried out with mean lesion size 29 mm . Overall diagnostic sensitivity was 66 % . For lesions not touching visceral pleura it was 74 % compared with 35 % where it was on the pleura ( P < 0.01 ) . For CT FNA 121 cases were carried out with mean lesion size 37 mm . The overall diagnostic sensitivity was 64 % . Rate of pneumothorax and ICC placement in EBUS GS was 1 and 0 % and in CTFNA was 28 and 6 % , with P < 0.001 for both . CONCLUSION Lesion location , in particular , connection to the visceral pleura , can improve decision-making in referral for either CT FNA or EBUS GS to maximize diagnostic yield and minimize pneumothorax rate RATIONALE Endobronchial ultrasound ( EBUS ) and electromagnetic navigation bronchoscopy ( ENB ) have increased the diagnostic yield of bronchoscopic diagnosis of peripheral lung lesions . However , the role of combining these modalities to overcome each individual technique 's limitations and , consequently , to further increase the diagnostic yield remains untested . OBJECTIVES A prospect i ve r and omized controlled trial involving three diagnostic arms : EBUS only , ENB only , and a combined procedure . METHODS All procedures were performed via flexible bronchoscopy and transbronchial forceps biopsies were obtained without fluoroscopic guidance . In the combined group , after electromagnetic navigation , the ultrasound probe was passed through an extended working channel to visualize the lesion . Biopsies were taken if ultrasound visualization showed that the extended working channel was within the target . Primary outcome was diagnostic yield . The reference " gold st and ard " was a surgical biopsy if bronchoscopic biopsy did not reveal a definite histological diagnosis compatible with the clinical presentation . Secondary outcomes were yields by size , lobar distribution , and lesion pathology . Complication rates were also documented . MEASUREMENTS AND MAIN RESULTS Of the 120 patients recruited , 118 had a definitive histological diagnosis and were included in the final analysis . The diagnostic yield of the combined procedure ( 88 % ) was greater than EBUS ( 69 % ) or ENB alone ( 59 % ; p = 0.02 ) . The combined procedure 's yield was independent of lesion size or lobar distribution . The pneumothorax rates ranged from 5 to 8 % , with no significant differences between the groups . CONCLUSIONS Combined EBUS and ENB improves the diagnostic yield of flexible bronchoscopy in peripheral lung lesions without compromising safety BACKGROUND Endobronchial ultrasound ( EBUS ) is an accurate and relatively less invasive procedure for the diagnosis of lung lesions and mediastinal lymph node staging for lung cancer . We aim ed to evaluate the clinical utility and safety of this new EBUS service established in our hospital . METHODS Consecutive patients who underwent EBUS-transbronchial lung biopsy ( EBUS-TBLB ) for biopsy of peripheral pulmonary lesions or for transbronchial needle aspiration ( TBNA ) of mediastinal lymph node enlargement were included in this audit . Demographic and clinical data were obtained prospect ively . Diagnostic yield from the results of EBUS was compared to other clinical information obtained . RESULTS Thirty-eight patients underwent EBUS over a 10-month period . The yield from EBUS-TBLB was 62 % . The average size of the lung lesions biopsied was 3.5 cm and 62 % were located in the upper lobes . Malignancy was diagnosed in 14 cases and a benign aetiology in four . The yield from EBUS-TBNA was 88 % and the average size of the lymph nodes was 2.3 cm . The lymph nodes were all located in the subcarinal station except for two that were in the lower paratracheal station . Malignancy was diagnosed in 10 cases on TBNA and 4 cases had benign pathology . There was one complication seen ( small pneumothorax ) . CONCLUSION EBUS is safe and an effective method for both , diagnosis of peripheral pulmonary lesions and staging for lung cancer BACKGROUND Prior case series have shown promising diagnostic sensitivity for CT scan-guided bronchoscopy . METHODS This was a prospect i ve r and omized trial comparing CT scan-guided bronchoscopy vs conventional bronchoscopy for the diagnosis of lung cancer in peripheral lesions and mediastinal lymph nodes . All procedures were performed using a protocol ized number of passes for forceps , transbronchial needles , and brushes . Cytologists and pathologists were blinded as to bronchoscopy type . Patients with negative results underwent open surgical biopsy ( for nodules or lymph nodes ) or were observed for > or = 2 years if they had a nodule < 1 cm in size . RESULTS Fifty patients were enrolled into the study ( CT scan-guided bronchoscopy , 26 patients ; conventional bronchoscopy , 24 patients ) . Two patients , one from each arm , dropped out of the study . Ultimately , 36 patients were proven to have cancer , and 27 of these patients ( 75 % ) had their diagnosis made by bronchoscopy . The sensitivity for malignancy of CT scan-guided bronchoscopy vs conventional bronchoscopy for peripheral lesions was similar ( 71 % vs 76 % , respectively ; p = 1.0 ) . The sensitivity for malignancy of CT guided bronchoscopy vs conventional bronchoscopy for mediastinal lymph nodes was higher ( 100 % vs 67 % , respectively ) but did not reach statistical significance ( p = 0.26 ) . On a per-lymph-node basis , there was a trend toward higher diagnostic accuracy with CT scan guidance ( p = 0.09 ) . The diagnostic yield was higher in larger lesions ( p = 0.004 ) and when CT scanning confirmed target entry ( p = 0.001 ) . CONCLUSION We failed to demonstrate a significant difference between CT scan-guided bronchoscopy and conventional bronchoscopy for the diagnosis of lung cancer in peripheral lesions and mediastinal lymph nodes . Further study of improved steering methods combined with CT scan guidance for the diagnosis of lung cancer in peripheral lesions is warranted STUDY OBJECTIVES The aim of our study was to compare the diagnostic yield of two bronchoscopic procedures : endobronchial ultrasound-driven transbronchial biopsy ( EBUS-TBB ) and transbronchial biopsy ( TBB ) in peripheral pulmonary lesions . DESIGN Prospect i ve , r and omized , blinded study . SETTING University Hospital of Rome , Italy . PATIENTS AND METHODS We examined 799 patients with peripheral lung lesions using bronchoscopy . Patients who could undergo a complete clinical diagnostic follow-up ( n = 293 ) were enrolled in the study and r and omly assigned to EBUS-TBB or TBB . We performed these two procedures on 221 patients ( 97 EBUS-TBB and 124 TBB ) . Patients in whom biopsies were not diagnostic underwent more invasive procedures to obtain a final diagnosis , and a complete follow-up was possible in 206 patients ( 87 EBUS-TBB and 119 TBB ) . RESULTS Lung cancer was diagnosed in 61 patients in the EBUS-TBB group and in 83 patients in the TBB group . Pulmonary diseases other than cancer were diagnosed in 26 patients and 36 patients , respectively . For patients with lung cancer , sensitivity was 0.79 in the EBUS group and 0.55 in the TBB group ( p = 0.004 ) , and accuracy was 0.85 and 0.69 , respectively ( p = 0.007 ) . The analysis of a subset of patients with lesions > 3 cm showed no significant difference in diagnostic ability between the two procedures . In lesions < 3 cm , we found a considerable decline in TBB sensitivity and accuracy ( 0.31 and 0.50 ) while EBUS-TBB maintained their diagnostic yield ( 0.75 and 0.83 ) [ p = 0.0002 and p = 0.001 , respectively ] . A similar difference was observed when we compared the sensitivity of the two procedures in lesions < 2 cm ( 0.23 vs 0.71 , p < 0.001 ) . CONCLUSIONS EBUS-TBB can be an important option in the early diagnosis of peripheral lung cancer , especially in small-sized lesions and in patients who are not eligible for surgery STUDY OBJECTIVES Transbronchial biopsy ( TBBX ) for solitary pulmonary nodules ( SPNs ) is usually performed under fluoroscopic guidance , but the diagnostic yield depends on lesion size and varies widely . Nodules < 3 cm frequently can not be visualized fluoroscopically . An alternative guidance technique , endobronchial ultrasound ( EBUS ) , also allows visualization of pulmonary nodules . This study assessed the diagnostic yield of EBUS-guided TBBX in fluoroscopically invisible SPNs . DESIGN The study was a prospect i ve trial using a crossover design . PATIENTS AND METHODS All patients with SPNs and indications for bronchoscopy were included in the study . An EBUS-guided examination was performed in patients with fluoroscopically invisible nodules . The EBUS probe was introduced through a guide catheter into the presumed segment . If a typical ultrasonic picture of solid tissue could be seen , the probe was removed and the catheter left in place . The biopsy forceps were introduced and specimens taken . RESULTS One hundred thirty-eight consecutive patients with SPNs were examined . Of those , 54 patients presented with SPNs that could not be visualized with fluoroscopy . The mean diameter of the nodules was 2.2 cm . In 48 patients ( 89 % ) , the lesion was localized with EBUS , and in 38 patients ( 70 % ) the biopsy established the diagnosis . The 16 patients with undiagnosed SPNs were referred for surgical biopsy ; 10 of those lesions were malignant and 6 were benign . The diagnosis in nine patients ( 17 % ) saved the patients from having to undergo a surgical procedure . The only complication was a pneumothorax in one patient . CONCLUSIONS EBUS-guided TBBX is a safe and very effective method for SPNs that can not be visualized by fluoroscopy . The procedure may increase the yield of endoscopic biopsy in patients with these nodules and avert the need for surgical procedures PURPOSE We present our 7-year experience with coaxial computed tomography (CT)-guided cutting needle lung biopsy and evaluate the factors affecting risk of complications . MATERIAL AND METHOD Between June 2000 and March 2007 , we performed 225 CT-guided coaxial lung biopsies in 213 consecutive patients ( 161 men , 52 women ) . Lesion size , lesion depth , lesion location , needle-pleural angle , presence of pleural effusion , patient 's position , and complications secondary to biopsy procedure ( pneumothorax and bleeding ) were noted . Pneumothorax was grade d as mild , moderate , and severe . Bleeding complications were grade d as mild , moderate , and severe . RESULTS Two hundred twenty-five biopsy procedures were performed in 213 patients . The mean diameter of the lung lesion was 41.3+/-20.1 mm . The mean distance from the peripheral margin of the lesion to the pleura was 17.3+/-19.2 mm . After 225 procedures , there were 42 mild ( 18.6 % ) , 13 moderate ( 5.7 % ) , and 4 severe ( 1.7 % ) pneumothoraxes . Small hemoptysis occurred in 27 patients ( 12 % ) , and mild parenchymal hemorrhage occurred in 2 patients ( 0.8 % ) . The overall complication rate was 39.1 % . Although , a statistically significant correlation was found between female sex , presence of emphysema , lesion depth , and pneumothorax , none of these factors had a predictive value for pneumothorax . Although , statistically significant correlations were found between female sex , lesion size , and bleeding , only lesion size had a predictive value for bleeding . CONCLUSION The most frequent and important complications of this procedure are pneumothorax and bleeding . But any factor is the predictor of pneumothorax and lesion depth is a poor predictor of bleeding complication Studies suggest that screening with spiral computed tomography can detect lung cancers at a smaller size and earlier stage than chest radiography can . To evaluate low-radiation-dose spiral computed tomography and sputum cytology in screening for lung cancer , we enrolled 1,520 individuals aged 50 yr or older who had smoked 20 pack-years or more in a prospect i ve cohort study . One year after baseline scanning , 2,244 uncalcified lung nodules were identified in 1,000 participants ( 66 % ) . Twenty-five cases of lung cancer were diagnosed ( 22 prevalence , 3 incidence ) . Computed tomography alone detected 23 cases ; sputum cytology alone detected 2 cases . Cell types were : squamous cell , 6 ; adenocarcinoma or bronchioalveolar , 15 ; large cell , 1 ; small cell , 3 . Twenty-two patients underwent curative surgical resection . Seven benign nodules were resected . The mean size of the non-small cell cancers detected by computed tomography was 17 mm ( median , 13 mm ) . The postsurgical stage was IA , 13 ; IB , 1 ; IIA , 5 ; IIB , 1 ; IIIA , 2 ; limited , 3 . Twelve ( 57 % ) of the 21 non-small cell cancers detected by computed tomography were stage IA at diagnosis . Computed tomography can detect early-stage lung cancers . The rate of benign nodule detection is high Background : Peripheral lung lesions are increasing in numbers . Endoscopic diagnosis is essential for the prevention of unnecessary operations . Conventional diagnostic procedures have limitations in availability and results . Objectives : Endobronchial ultrasonography ( EBUS ) was investigated as a means to guide transbronchial lung biopsy , to reduce the discomfort during the procedure and to improve diagnostic accuracy . Methods : In 50 cases , we performed transbronchial lung biopsy combined with EBUS and fluoroscopic guidance . The results were compared to 42 controls assessed by fluoroscopy only . Results : In 38 cases ( 76 % ) , EBUS could describe the peripheral lesion ( 33 from inside , including 9 cases with difficulties in fluoroscopic observation , and 5 from an adjacent bronchus , indicating the correct location of the lesion ) . If successfully placed inside , a change in the patient ’s position was not required , which helped to reduce patient discomfort . Lung cancer was diagnosed in 24 patients and benign disease in 25 patients ; in 1 case diagnosis remained unknown . When the EBUS probe could be introduced inside the lesion , the sensitivity for cancer diagnosis and specificity for cancer exclusion were 100 % , respectively ( 15/15 , 18/18 ) . Compared to the controls in whom the biopsy site was determined by fluoroscopy only , the sensitivity tended to be superior by EBUS , although it did not reach statistical significance ( p = 0.06 ) . However , specificity and accuracy were statistically significant ( both p = 0.02 ) . Conclusions : When the lesion can be correctly described by EBUS from inside the lesion , EBUS is useful to guide transbronchial lung biopsy , can contribute to a reduction in patient discomfort and improves the accuracy of diagnosis . Additional navigation tools to increase correct positioning of the EBUS probe are desirable CT bronchus sign ( BS ) design ates a bronchus leading directly to a peripheral pulmonary lesion . The objective of this investigation is to determine the contribution of BS-guided bronchoscopic multiple diagnostic procedures ( BMDPs ) to the diagnostic yield of solitary nodules or masses ( SPNMs ) suspected of pulmonary carcinoma ( PC ) . A prospect i ve study was carried out in 92 patients with a 2–5 cm diameter SPNM at the level of third to fifth bronchial branching and without endobronchial tumors . Within 10 days after 2-mm CT scans were done , in each of 92 , bronchial washing ( BW ) , brushing ( BR ) , transbronchial needle aspiration ( TBNA ) and transbronchial lung biopsy ( TBB ) were performed respectively , via fiberoptic bronchoscopy ( FB ) under fluoroscopic guidance . In 40 ( 82 % ) of 49 with BS and in 19 ( 44 % ) of 43 without BS , FB established the diagnosis ( p < 0.01 ) . In 84 cases of PC , BW , BR , TBNA and TBB provided the diagnostic yields of 4 % ( 3 ) , 26 % ( 22 ) , 57 % ( 48 ) and 49 % ( 41 ) , respectively ; the combined yield reached 68 % ( 57 ) . A metastasis and a tuberculoma were diagnosed exclusively by TBB , and TBNA , respectively . All differences of diagnostic yield except that between TBNA and TBB ( p > 0.05 ) were determined to be significant ( p < 0.05 ) . Thoracotomy verified diagnosis in 48 of 59 cases diagnosed and 19 of 33 undiagnosed by FB , and various tissue biopsies or clinical follow-up in 11 diagnosed and 14 undiagnosed by FB . The above data suggest that in the diagnosis of PC as a SPNM at the level of third – fifth bronchial branching , combining the guidance of CT BS , and BMDPs under fluoroscopic guidance can increase the yield considerably |
10,307 | 18,219,828 | There is encouraging evidence suggesting that P hybridus may be an effective herbal treatment for seasonal ( intermittent ) AR .
There are also promising results generated for other herbal products , particularly Aller-7 , Tinospora cordifolia , Perilla frutescens , and several Chinese herbal medicines . | OBJECTIVE To evaluate the efficacy of herbal medicines for the treatment of allergic rhinitis ( AR ) . | Soy sauce ( Shoyu ) is a traditional fermented seasoning of East Asian countries and is available throughout the world . We obtained polysaccharides from raw soy sauce , and showed the anti-allergic activities of these Shoyu polysaccharides ( SPS ) in vitro and in vivo . The present study determined whether oral supplementation of SPS is an effective intervention for patients with seasonal allergic rhinitis . In an 8-week r and omized , double-blind , placebo-controlled parallel group study , patients with mild seasonal allergic rhinitis were treated with 600 mg of SPS ( n=25 ) or placebo ( n=26 ) each day . After 4 weeks of treatment with SPS , symptom scores such as sneezing , nasal stuffiness , and hindrance of daily life were significantly different ( P<0.05 ) from those in placebo-treated groups . The total symptom score , calculated from the sum of individual scores , showed a significant difference ( P<0.05 ) between the 2 groups after 4 - 8 weeks . On nasal examination by the investigator , the color of the inferior turbinate in SPS-treated patients was significantly different ( P<0.05 ) from that in placebo-treated patients between weeks 4 and 8 , and the nasal symptom scores for color of inferior turbinate , watery discharge , and state of sniffles were also significantly different ( P<0.05 ) from those in the placebo-treated group after 8 weeks . In conclusion , SPS of soy sauce improved the quality of life of patients with seasonal allergic rhinitis , and soy sauce would be useful in an anti-allergic therapy utilizing daily foods Abstract Objectives : To compare the efficacy and tolerability of butterbur ( Petasites hybridus ) with cetirizine in patients with seasonal allergic rhinitis ( hay fever ) . Design : R and omised , double blind , parallel group comparison . Setting : Four outpatient general medicine and allergy clinics in Switzerl and and Germany . Participants : 131 patients were screened for seasonal allergic rhinitis and 125 patients were r and omised ( butterbur 61 ; cetirizine 64 ) . Interventions : Butterbur ( carbon dioxide extract tablets , ZE 339 ) one tablet , four times daily , or cetirizine , one tablet in the evening , both given for two consecutive weeks . Main outcome measures : Scores on SF-36 question naire and clinical global impression scale . Results : Improvement in SF-36 score was similar in the two treatment groups for all items tested hierarchically . Butterbur and cetirizine were also similarly effective with regard to global improvement scores on the clinical global impression scale ( median score 3 in both groups ) . Both treatments were well tolerated . In the cetirizine group , two thirds ( 8/12 ) of reported adverse events were associated with sedative effects ( drowsiness and fatigue ) despite the drug being considered a non-sedating antihistamine . Conclusions : The effects of butterbur are similar to those of cetirizine in patients with seasonal allergic rhinitis when evaluated blindly by patients and doctors . Butterbur should be considered for treating seasonal allergic rhinitis when the sedative effects of antihistamines need to be avoided . What is already known on this topic Seasonal allergic rhinitis ( hay fever ) is common in countries with temperate climates . Most patients have their symptoms treated for short periods , particularly during peaks in atmospheric pollen count What this study adds After two weeks , the effects of butterbur and cetirizine were comparable in patients with hay fever Butterbur produced fewer sedating effects than cetirizine Butterbur should be considered when the sedating effects of antihistamines must be 1 The seed of Butyrospermum parkii yields shea butter which according to local traditional healers relieves inflammation of the nostrils . 2 Since there is as yet no absolutely satisfactory nasal decongestant in clinical use , it was decided to investigate the effects of shea butter in nasal congestion . The substance was prepared in the laboratory . 3 The human subjects used were those suffering from rhinitis with moderate to severe nasal congestion . They were divided into the test group which received shea butter , the control group which was treated with xylometazoline and the ' placebo ' group which received white petroleum jelly B.P. 4 The results showed that nasal congestion was relieved more satisfactorily in the test group than in the other two groups . 5 It is concluded that shea butter may prove more efficacious in nasal congestion than conventional nasal drops The present study was undertaken to determine whether oral supplementation with rosmarinic acid ( RA ) is an effective intervention for patients with SAR . In addition , the anti‐inflammatory mechanism of RA also estimated in the ear edema models . Clinical trial : Patients were treated daily with RA ( 200 mg or 50 mg ) or placebo for 21 days . Patients recorded symptoms daily and profiles of infiltrating cells and concentration of cytokines were measured in nasal lavage fluid . Compared to placebo , supplementation with RA result ed in a significant decrease in responder rates for each symptom . RA also significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid . Animal Study : Topical application RA showed anti‐inflammatory activity 5‐hours after 12‐tetradecanoylphorbol 13‐acetate ( TPA ) treatment with marked inhibition of neutrophil infiltration . Up regulation of ICAM‐1 , VCAM‐1 cyclooxygenase‐2 ( COX‐2 ) , KC and MIP‐2 by TPA were markedly reduced by pre‐treatment with extract of perilla ( PE ) or RA . Reactive oxygen radical production detected as thiobarbituric acid reactive substance ( TBARS ) , lipid peroxide ( LPO ) and 8‐hydroxy‐2'deoxyguanosine ( 8OH‐dG ) , by double treatment of TPA was reduced by pretreatment with PE or RA . RA is an effective intervention for SAR that is mediated by inhibition of PMNL infiltration . This effect of RA is due to two independent mechanisms : inhibition of the inflammatory response and scavenging of ROS OBJECTIVES To investigate whether the efficacy and safety of Butterbur extract Ze339 are related to dosage when administered to patients with intermittent allergic rhinitis . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled , parallel-group comparison . SETTING Multicenter , including 6 outpatient general medicine and allergy clinics . PATIENTS One hundred eighty-six patients were r and omized ( Butterbur Ze339 high dose , 60 ; low dose , 65 ; and placebo , 61 patients ) . Established diagnostic criteria for intermittent allergic rhinitis were confirmed by skin allergy tests in all patients . INTERVENTIONS High-dose group , 1 tablet 3 times daily ; low-dose group , 1 tablet twice daily ; or matching placebo . All groups were treated for 2 consecutive weeks . MAIN OUTCOME MEASURES The main efficacy variable was change in symptoms from baseline to end point during the daytime . The secondary efficacy variables were Clinical Global Impression score , change in symptoms from baseline to treatment day 7 , and responder rates . Statistical analysis was prospect i ve , on an intention-to-treat basis . RESULTS Improvement in the main efficacy variable was significantly superior in the Butterbur Ze339 groups , relative to placebo , and a significant dose relationship was observed between the 2 Butterbur doses . The clinicians ' assessment of efficacy and the overall responder rates were significantly superior for the active groups compared with placebo . The incidence and type of adverse events were indistinguishable across the herbal treatment and placebo groups . CONCLUSIONS Butterbur Ze339 is an effective treatment for intermittent allergic rhinitis symptoms and is well tolerated . The effects of this herbal medicine are clear to patients and physicians in a double-blind evaluation against placebo Background There are presently no placebo‐controlled data regarding the effects of butterbur ( BB ) on subjective and objective outcomes in patients with perennial allergic rhinitis OBJECTIVE To observe the therapeutic effect of Kebimin decoction ( KD ) on allergic rhinitis ( AR ) and its effect on blood levels of nitric oxide ( NO ) and superoxide dismutase ( SOD ) activity . METHODS Eighty-two AR patients were r and omly divided into two groups , the treated group and the control group , 41 in each group . To the treated group , KD was given one dose per day for 10 days as one therapeutic course and 1 - 3 courses were given successively . The control group was treated with Xinfang Rhinitis capsule for 30 days . Blood levels were determined and compared before and after treatment . RESULTS The total effective rate in the treated group was 93 % , which was better than that in the control group ( 51 % ) , the difference was significant ( chi 2 = 17.704 , P < 0.01 ) . Serum level of NO was higher and that of SOD activity was lower in the AR patients than that in healthy persons ( P < 0.01 ) , KD could significantly lower the former and increase the latter ( P < 0.01 ) . CONCLUSION The therapeutic effect of KD in treating AR was significant , its mechanism might be related with the lowering of NO and increasing of SOD activity in serum , as well as the scavenging of oxygen free radical BACKGROUND Butterbur ( Petasites hybridus ) contains the active ingredient petasin , which exhibits antileukotriene and antihistamine activity . Previous studies of intermittent allergic rhinitis ( IAR ) have demonstrated a comparable response to butterbur compared with a histamine H1-receptor antagonist on the 36-Item Short-Form Health Survey quality -of-life score . However , there has been no placebo-controlled study of the effects of butterbur use on objective and subjective outcomes in IAR . OBJECTIVE To evaluate the effects of treatment with butterbur vs placebo on objective and subjective outcomes in IAR . METHODS A double-blind , placebo-controlled , crossover study was carried out during the grass pollen season in Tayside , Scotl and . Thirty-five patients ( 14 men and 21 women ) with IAR received butterbur , 50 mg twice daily , or placebo for 2 weeks . Domiciliary measurements were taken in the morning and evening for peak nasal inspiratory flow ( PNIF ) ( the primary outcome variable ) , nasal and eye symptoms , and rhinoconjunctivitis-specific quality -of-life score . RESULTS Butterbur treatment had no significant effect on PNIF , total nasal symptom score , eye symptom score , or quality of life compared with placebo use . Mean ( SEM ) morning and evening PNIF values were 107 ( 6 ) and 114 ( 6 ) L/min , respectively , for butterbur vs 105 ( 6 ) and 117 ( 6 ) L/min for placebo . Mean ( SEM ) morning and evening total nasal symptom scores ( maximum total score , 12 ) were 3.4 ( 0.4 ) and 3.5 ( 0.4 ) , respectively , for butterbur vs 3.7 ( 0.3 ) and 3.8 ( 0.4 ) for placebo . CONCLUSIONS There was no significant clinical efficacy of butterbur use vs placebo use on objective and subjective outcomes in IAR . Further studies are now indicated to investigate the use of butterbur in persistent allergic rhinitis BACKGROUND Butterbur or Petasites hybridus is an herbal remedy that exhibits antihistamine and antileukotriene activity and has been shown to attenuate the response to adenosine monophosphate challenge in patients with allergic rhinitis and asthma . However , no data are available regarding its effects on the histamine and allergen cutaneous response . OBJECTIVE To evaluate the effects of butterbur compared with fexofenadine and montelukast on the histamine and allergen wheal and flare cutaneous responses . METHODS Atopic patients were r and omized into a double-blind , double-dummy , crossover study to receive for 1 week butterbur , 50 mg twice daily ( 8 AM and 10 PM ) ; fexofenadine , 180 mg once daily ( 10 PM ) , and placebo once daily ( 8 AM ) ; montelukast , 10 mg once daily ( 10 PM ) , and placebo once daily ( 8 AM ) ; or placebo twice daily ( 8 AM and 10 PM ) . Patients attended the department at 10 AM and had measurements of the cutaneous wheal and flare responses to histamine , allergen , and saline control at 10-minute intervals for 60 minutes . RESULTS Twenty patients completed the study . The mean + /- SE histamine wheal and flare responses , respectively , were significantly attenuated ( P < .05 ) by fexofenadine ( 9.4 + /- 1.8 mm2 and 13.5 + /- 3.2 mm2 ) compared with placebo ( 15.5 + /- 3.3 mm2 and 179.8 + /- 74.3 mm2 ) but not by butterbur ( 16.4 + /- 2.1 mm2 and 297.7 + /- 121.2 mm2 ) or montelukast ( 19 + /- 1.9 mm2 and 240.2 + /- 66.6 mm2 ) . The allergen wheal and flare responses , respectively , were also significantly attenuated ( P < .05 ) by fexofenadine ( 31.1 + /- 6.3 mm2 and 256.9 + /- 86.5 mm2 ) compared with placebo ( 65.4 + /- 15.2 mm2 and 1,014.5 + /- 250.0 mm2 ) but not by butterbur ( 50.4 + /- 9.2 mm2 and 1,110.3 + /- 256.1 mm2 ) or montelukast ( 58.8 + /- 9.1 mm2 and 1,463.6 + /- 295.6 mm2 ) . CONCLUSIONS Butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared with placebo , whereas mediator antagonism with fexofenadine but not montelukast produced significant attenuation . This finding would suggest that butterbur may not be effective in allergic skin disease BACKGROUND Allergic rhinitis ( AR ) is a frequent disease affecting up to 20 % of the population . AR causes a hypersensitivity reaction , which results in inflamed nasal mucosa and nasal congestion . Negative pressure generated during inspiration in the nasal airway secondary to nasal congestion may lead to nasal collapse , airway obstruction , and an increased number of sleep microarousals . Sleep disturbances and microarousals can detrimentally affect daytime energy levels , mood , and daytime function . It is unknown whether treatment directed to reduce congestion may reduce these microarousals , sleep problems , and , consequently , associated daytime fatigue . OBJECTIVE We sought to determine whether reducing nasal congestion with nasal steroids will reduce sleep complaints and daytime sleepiness . METHOD We enrolled 20 subjects in a double-blind , placebo-controlled study using Balaam 's Design . Patients were treated with topical nasal corticosteroids or placebo . Subjective data were collected by use of a daily diary , which focused on nasal symptoms , sleep , and daytime sleepiness . RESULTS The results demonstrated that nasal congestion and subjective sleep improved significantly in the topical corticosteroid-treated subjects but not in the placebo group . Sleepiness improved , but not significantly ( p = 0.08 ) . CONCLUSION Often , people with perennial allergies may attribute their daytime fatigue to causes such as the side effects of medications , when in fact , the fatigue may be a result of nasal congestion and associated sleep fragmentation . Decreasing nasal congestion with nasal steroids may improve sleep , daytime fatigue , and the quality of life of patients with AR Abstract Results of a crossover double-blind trial on 110 bronchial asthma patients with leaves of Tylophora indica and of spinach ( placebo ) are presented . The dose was one leaf daily for 6 days to be chewed and swallowed early in the morning . A 12 week follow-up was done . At the end of one week , 62 per cent of the Tylophora group had complete to moderate relief in symptoms , as compared with 28 per cent of the placebo group . At 4 weeks , the respective figures were 37 per cent and 11 per cent ; at 8 weeks , 30 per cent and 7.4 per cent ; and at 12 weeks , 16 per cent and zero per cent . The incidence of side effects , such as sore mouth , loss of taste for salt , and /or morning nausea and vomiting was 53 per cent in the Tylophora group and 9 per cent in the placebo group . There appeared to be a correlation between the incidence of side effects and degree of improvement . After crossover at the end of one week , 50 per cent of the Tylophora group had complete to moderate relief as compared with 11 per cent of the placebo group . The authors are not aware of any other drug which , when administered in a small dose once a day for 6 days only , will suppress the symptoms of allergic rhinitis and /or asthma for 8 to 12 weeks in a significant number of patients . It is postulated that irritative effects of the juice of the Tylophora leaf on the mucous membranes of the mouth , tongue , and stomach somehow suppress or diminish the response of the nasobronchial tissue to an inhalant allergen through some reflex mechanism Allergic rhinitis is the most frequently occurring immunological disorder . It affects men , women and children and represents significant cost in terms of suffering and loss of productivity . Allergy is termed as an excessive reaction to an environmental allergen . Pollen , mold , dust , mite and animal allergens that contact the nasal or eye lining cause sneezing , nasal congestion and itchy , watery , swollen , red eyes . Although a broad spectrum of therapeutic options is available , the treatment of allergic rhinitis appears to be far from satisfactory . A novel polyherbal formulation ( PF ; Aller-7/NR-A2 ) comprising seven medicinal herbal extracts was assessed in a multicenter clinical trial involving 545 patients ( 321 males and 224 females ) aged 18 - 59 years for 12 weeks to evaluate its clinical efficacy in patients suffering from allergic rhinitis . A total of 171 patients participated in double-blind , r and omized , placebo-controlled studies in three centers , while 374 patients were included in the open-label studies in 11 centers . The three major symptoms ( sneezing , rhinorrhea and nasal congestion ) of allergic rhinitis were significantly reduced . Significant improvement was also observed in absolute eosinophil count , mucociliary clearance time , peak expiratory flow rate and peak nasal flow rate . No serious adverse events that warranted cessation of treatment were observed . Minor adverse effects were noted in both the treatment and placebo groups . Thus , this study demonstrates that Aller-7/NR-A2 is well tolerated and efficacious in patients with allergic rhinitis BACKGROUND Herbal therapies have been widely used in allergic rhinitis ( AR ) , but none have been shown to be effective in controlled scientific clinical trials . OBJECTIVE The aim of this study was to test the effects of the Chinese herbal formulation Biminne in patients with moderate to severe perennial AR . METHODS In a r and omized , double-blind , placebo-controlled clinical trial , 58 patients were r and omized to receive either Biminne capsules ( n = 26 ) or placebo ( n = 32 ) in doses of five capsules twice a day for 12 weeks . Main outcomes were measured by changes in symptom diaries , quality of life scores , patients ' evaluations of improvement on visual analog scores , and physicians ' overall evaluation . Total serum immunoglobulin E was measured in all patients without knowledge of which group they were in . After 1 year we performed a r and omized , double-blind , dose-response study in 22 patients who had previously received placebo . RESULTS The trial outcomes evaluated by four instruments showed a statistically significant improvement in some of the symptoms of AR , whereas others exhibited a positive trend that did not reach statistical significance . Followup 1 year after completion of the trial suggested that benefit of the treatment persisted . A pilot dose-response study showed both half and full strengths were effective . Total serum immunoglobulin E was reduced after the herbal treatment . CONCLUSIONS Our results suggest the Biminne formulation is effective in treatment of perennial AR . Its mode of action is unknown Ninety-eight individuals took part in a double-blind r and omized study comparing the effects of a freeze-dried preparation of Urtica dioica ( stinging nettles ) with placebo on allergic rhinitis . Sixty-nine individuals completed the study . Assessment was based on daily symptom diaries , and global response recorded at the follow-up visit after one week of therapy . Urtica dioica was rated higher than placebo in the global assessment s. Comparing the diary data Urtica dioica was rated only slightly higher CONTEXT Chinese herbal medicine ( CHM ) is widely used to treat seasonal allergic rhinitis ( SAR ) , however , evidence of efficacy is lacking . OBJECTIVE To evaluate the efficacy of a Chinese herbal formulation for the treatment of SAR . DESIGN R and omized , double blind , placebo controlled trial . SETTING RMIT Chinese Medicine Clinic . PATIENTS 55 patients with seasonal allergic rhinitis ( active 28 , placebo 27 ) . INTERVENTIONS CHM extract capsule ( containing 18 herbs ) or placebo , given daily for 8 weeks . MAIN OUTCOME MEASURES The primary measure of efficacy were changes in severity of nasal and non-nasal symptoms using a Five Point Scale ( FPS ) measured by both patients and the practitioner . The secondary measure was the change in score for the domains measured in the Rhinoconjunctivitis and Rhinitis Quality of Life Question naire ( RQLQ ) assessed by patients . RESULTS Forty-nine patients completed the study ( active 24 , placebo 25 ) . After eight weeks , the severity of nasal symptoms and non-nasal symptoms were significantly less in the active treatment group than in the control group , both for measurements made by patients and those by the practitioner . Comparison of active and placebo treatment groups RQLQ scores also indicated significant beneficial effects of treatment ( end point Section 1 : P < 0.05 ; Section 2 : P < 0.01 ) . Intention-to-treat analyses of categorical items showed moderate to marked improvement rates were 60.7 % and 29.6 % for active and placebo respectively . Eleven patients reported mild adverse events including 1 withdrawn from the trial . CONCLUSIONS This CHM formulation appears to offer symptomatic relief and improvement of quality of life for some patients with seasonal allergic rhinitis BACKGROUND Intermittent allergic rhinitis ( IAR ) causes patients distress and impairs their work performance and quality of life . A variety of medicines are used by sufferers whose anguish frequently leads to trying new treatments , increasingly from herbal sources . METHODS Prospect i ve , r and omized , double-blind , parallel group comparison study of Butterbur extract ( Ze 339 ; 8 mg total petasine ; one tablet thrice-daily ) , fexofenadine ( Telfast 180 , one tablet once-daily ) and placebo in 330 patients . Protocol and analysis were according to the latest guidelines on new treatments for allergic rhinitis . The primary efficacy variable was a change in symptoms from baseline to endpoint during daytime . The secondary efficacy variables were : ( a ) as per primary variable ( evening/night ) ; ( b ) Physician 's global assessment ; ( c ) Responder rates . Safety was closely monitored . FINDINGS Both active treatments were individually significantly superior to placebo ( p<0.001 ) in improving symptoms of IAR , while there were no differences between the two active treatments ( p=0.37 ) . Superiority to placebo was similarly shown during the evening/night ( p<0.001 ) , by physicians ' own assessment and by responder rates . Both treatments were well tolerated . INTERPRETATION Butterbur Ze 339 and Fexofenadine are comparably efficacious relative to placebo . Despite being a herbal drug , Butterbur Ze 339 has now been subject to a series of well controlled trials and should be considered as an alternative treatment for IAR Extract of Perilla frutescens enriched for rosmarinic acid , a polyphenolic phytochemical , suppresses allergic immunoglobulin responses and inflammation caused by polymorphonuclear leukocytes ( PMNL ) in mice . However , few placebo-controlled clinical trials have examined the efficacy and safety of polyphenolic phytochemicals for treatment of allergic inflammatory diseases in humans . The present study determined whether oral supplementation with rosmarinic acid is an effective intervention for patients with seasonal allergic rhinoconjunctivitis ( SAR ) . In this 21-day , r and omized , double-blind , age-matched , placebo-controlled parallel group study , patients with mild SAR were treated daily with extract of Perilla frutescens enriched for rosmarinic acid ( 200 mg [ n = 10 ] or 50 mg [ n = 9 ] ) or placebo ( n = 10 ) . Patients recorded symptoms daily in a diary . Profiles of infiltrating cells and concentrations of eotaxin , IL-1β , IL-8 , and histamine were measured in nasal lavage fluid . Serum IgE concentrations and routine blood tests were also examined . As compared with placebo supplementation , supplementation with extract of Perilla frutescens enriched for rosmarinic acid result ed in a significant increase in responder rates for itchy nose , watery eyes , itchy eyes , and total symptoms ( P < 0.05 ) . Active treatment significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid ( P < 0.05 vs. placebo ) . Patients reported no adverse events , and no significant abnormalities were detected in routine blood tests . In conclusion , extract of Perilla frutescens enriched for rosmarinic acid can be an effective intervention for mild SAR at least partly through inhibition of PMNL infiltration into the nostrils . Use of this alternative treatment for SAR might reduce treatment costs for allergic diseases The efficacy of Tinospora cordifolia ( TC ) extract in patients of allergic rhinitis was assessed in a r and omized double blind placebo controlled trial . Seventy-five patients were r and omly given either TC or placebo for 8 weeks . They were clinical ly examined and Hb % , TLC , DLC and nasal smear was done . At the end of trial baseline investigations were repeated , drug decoded and results analyzed . With TC treatment 100 % relief was reported from sneezing in 83 % patients , in 69 % from nasal discharge , in 61 % from nasal obstruction and in 71 % from nasal pruritus . In placebo group , there was no relief in 79 % from sneezing , in 84.8 % from nasal discharge , in 83 % from nasal obstruction , and in 88 % from nasal pruritus . The difference between TC and placebo groups was highly significant . TLC increased in 69 % patients in drug treated group and in only 11 % with placebo . After TC , eosinophil and neutrophil count decreased and goblet cells were absent in nasal smear . After placebo , decrease in eosinophil and neutrophil count was marginal and goblet cells were present . TC significantly decreased all symptoms of allergic rhinitis . Nasal smear cytology and leukocyte count correlated with clinical findings . TC was well tolerated Previous studies have suggested that histamine and leukotrienes ( LTs ) play an important pathobiological role in IgE-mediated allergic diseases . In vitro studies suggested that an extract of Petasites hybridus ( Ze339 ) blocks LT synthesis in monocytes and granulocytes . Petasins are considered to be the pharmacologically active fraction within Ze339 . Patients suffering from allergic rhinitis received three times a day two tablets of Ze339 st and ardized to 8 mg petasins within a time period of 1 week . After 5 days of treatment , Ze339 significantly improved primary end points , which were day- and nighttime nasal symptoms . Nasal resistance , which was measured by rhinomanometry , gradually decreased as a consequence of Ze339 treatment reaching normal levels after 5 days ( rhinomanometry : from 403.5+/-62.0 to 844.8+/-38.8 ml ) . Levels of inflammatory mediators in nasal fluids and serum were measured 90 min after drug administration every day in the morning . After 5 days of treatment , a significant reduction of histamine ( from 153.7+/-32.1 to 53.0+/-8.4 pg/ml ) and LT levels ( LTB4 : from 313.1+/-46.5 to 180.6+/-32.2 pg/ml ; cysteinyl-LT : from 137.0+/-42.2 to 70.1+/-16.5 pg/ml ) could be observed . Moreover , quality -of-life scores significantly improved . The drug had no effect on the distribution of lymphocyte sub population s in the blood as well as on the capacity of blood leukocytes to generate cytokines and lipid mediators . These results suggest that Ze339 is effective in treating allergic rhinitis patients by decreasing levels of nasal inflammatory mediators Soy sauce ( Shoyu ) is a traditional fermented seasoning of East Asian countries and available throughout the world . We obtained polysaccharides from raw soy sauce , and showed the anti-allergic activities of these Shoyu polysaccharides ( SPS ) in vitro and in vivo . The present study determined whether oral supplementation of SPS is an effective intervention for patients with perennial allergic rhinitis . In a 4-week r and omized , double-blind , placebo-controlled parallel group study , patients with mild perennial allergic rhinitis were treated with 600 mg of SPS ( n=11 ) or placebo ( n=10 ) each day . After 4 weeks of treatment with SPS , a reduction in symptom scores for runny nose , sore throat , and itchy eyes were significantly changed from the baseline within the group ( p<0.05 ) , but no change in these scores was observed over 4 weeks of treatment in the placebo group . However , differences in the symptom scores during the study period were not significantly different between the groups . The total symptom score , calculated from the sum of individual scores , showed a significant difference between the 2 groups after 4 weeks of treatment ( p<0.05 ) . The efficacy of global symptoms score , which was defined as the adjusted mean change from baseline during 4 weeks of treatment , also showed a significant improvement in the SPS group ( p<0.05 ) . An overall evaluation of the medication 's effectiveness after 4 weeks treatment showed significant differences between the SPS- and placebo-treated groups ( p<0.05 ) . In conclusion , SPS of soy sauce improved the quality of life for patients with perennial allergic rhinitis , and soy sauce would be useful in an anti-allergic therapy utilizing everyday foods Background Butterbur ( BB ) or Petasites hybridus , a herbal remedy , exhibits in vitro inhibition of cysteinyl leukotriene bio synthesis . However , no placebo‐controlled studies have been performed to evaluate the effectiveness of BB on objective outcomes such as nasal provocation testing in seasonal allergic rhinitis ( SAR ) BACKGROUND Herbal products are widely used by consumers as alternatives to prescription drugs in treating symptoms of allergic rhinitis . However , there have been few placebo-controlled clinical trials that have examined the efficacy or safety of these products . Although grapeseed extract ( GSE ) is an herbal that is marketed for treating allergic rhinitis , its efficacy is unproven . OBJECTIVE The aim of this study was to compare the efficacy and safety of GSE with placebo in the treatment of seasonal allergic rhinitis ( SAR ) . METHODS This was a r and omized , double-blind , placebo-controlled study of GSE 100 mg , twice daily , versus placebo . Patients with SAR and skin prick test sensitivity to ragweed were r and omized to 8 weeks of active treatment or placebo which was begun before the ragweed pollen season . Outcomes included : daily symptom diary scores recorded by patients , rhinitis quality of life scores at baseline and after 4 and 8 weeks of treatment ; and requirements for rescue chlorpheniramine . Safety was monitored with routine laboratory studies . RESULTS Over 8 weeks of treatment , no significant differences were observed between active and placebo groups in rhinitis quality of life assessment s , symptom diary scores , or requirements for rescue antihistamine . No significant laboratory abnormalities were detected . CONCLUSIONS This study did not show trends supporting the efficacy of GSE in the treatment of SAR |
10,308 | 22,882,130 | Maternal infection as well as respiratory distress syndrome ( RDS ) & neonatal sepsis ( NS ) were not different between the two groups .
Based on the available evidence , ID in pregnancies complicated with PPROM between 28 and 34 weeks carries some maternal and neonatal risks with no added benefits . | OBJECTIVE To assess the effects of intentional delivery ( ID ) over expectant management ( EM ) in pregnancies complicated by preterm prelabour rupture of membranes ( PPROM ) between 28 and 34 weeks of gestation on maternal and neonatal outcomes . | CONTEXT Half of all cases of cerebral palsy ( CP ) occur in term infants , for whom risk factors have not been clearly defined . Recent studies suggest a possible role of chorioamnionitis . OBJECTIVE To determine whether clinical chorioamnionitis increases the risk of CP in term and near-term infants . DESIGN , SETTING , AND PATIENTS Case-control study nested within a cohort of 231 582 singleton infants born at 36 or more weeks ' gestation between January 1 , 1991 , and December 31 , 1998 , in the Kaiser Permanente Medical Care Program , a managed care organization providing care for more than 3 million residents of northern California . Case patients were identified from electronic records and confirmed by chart review by a child neurologist , and comprised all children with moderate to severe spastic or dyskinetic CP not due to postnatal brain injury or developmental abnormalities ( n = 109 ) . Controls ( n = 218 ) were r and omly selected from the study population . MAIN OUTCOME MEASURE Association between clinical chorioamnionitis and increased risk of CP in term and near-term infants . RESULTS Most CP cases had hemiparesis ( 40 % ) or quadriparesis ( 38 % ) ; 87 % had been diagnosed by a neurologist and 83 % had undergone neuroimaging . Chorioamnionitis , considered present if a treating physician made a diagnosis of chorioamnionitis or endometritis clinical ly , was noted in 14 % of cases and 4 % of controls ( odds ratio [ OR ] , 3.8 ; 95 % confidence interval [ CI ] , 1.5 - 10.1 ; P = .001 ) . Independent risk factors identified in multiple logistic regression included chorioamnionitis ( OR , 4.1 ; 95 % CI , 1.6 - 10.1 ) , intrauterine growth restriction ( OR , 4.0 ; 95 % CI , 1.3 - 12.0 ) , maternal black ethnicity ( OR , 3.6 ; 95 % CI , 1.4 - 9.3 ) , maternal age older than 25 years ( OR , 2.6 ; 95 % CI , 1.3 - 5.2 ) , and nulliparity ( OR , 1.8 ; 95 % CI , 1.0 - 3.0 ) . The population -attributable fraction of chorioamnionitis for CP is 11 % . CONCLUSION Our data suggest that chorioamnionitis is an independent risk factor for CP among term and near-term infants BACKGROUND As the interval between rupture of the fetal membranes at term and delivery increases , so may the risk of fetal and maternal infection . It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another . METHODS We studied 5041 women with prelabor rupture of the membranes at term . The women were r and omly assigned to induction of labor with intravenous oxytocin ; induction of labor with vaginal prostagl and in E2 gel ; or expectant management for up to four days , with labor induced with either intravenous oxytocin or vaginal prostagl and in E2 gel if complications developed . The primary outcome was neonatal infection . Secondary outcomes were the need for cesarean section and women 's evaluations of their treatment . RESULTS The rates of neonatal infection and cesarean section were not significantly different among the study groups . The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group , 3.0 percent for the induction-with-prostagl and in group , 2.8 percent for the expectant-management ( oxytocin ) group , and 2.7 percent for the expectant-management ( prostagl and in ) group . The rates of cesarean section ranged from 9.6 to 10.9 percent . Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management ( oxytocin ) group ( 4.0 percent vs. 8.6 percent , P<0.001 ) , as was postpartum fever ( 1.9 percent vs. 3.6 percent , P=0.008 ) . Women in the induction groups were less likely to say they liked " nothing " about their treatment than those in the expectant-management groups . CONCLUSIONS In women with prelabor rupture of the membranes at term , induction of labor with oxytocin or prostagl and in E2 and expectant management result in similar rates of neonatal infection and cesarean section . Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management . Women view induction of labor more positively than expectant management We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 Objective To compare 12-hour and 72-hour expectant management of premature rupture of membranes ( PROM ) in singleton term pregnancies . Methods In a prospect i ve , nonr and omized study , 566 low-risk women with singleton term pregnancies presenting with PROM were assigned to either 12-hour or 72-hour expectant management . Patients who had not entered labor at the end of the assigned period were induced with oxytocin . The pregnancy outcome of both methods was compared with regard to infectious complications and method of delivery . Results There was no statistical difference in the rate of chorioamnionitis between the 12-hour and 72-hour expectant management groups ( 11.7 versus 12.7 % ; relative risk [ RR ] 0.9 , 95 % confidence interval [ CI ] 0.6 - 1.5 ; P = .83 ) . Cesareans were performed to a similar degree in both groups ( 4.7 versus 6.7 % ; RR 0.7 , 95 % CI 0.3 - 1.4 ; P = .39 ) . Fifty-five percent of the 12-hour group underwent oxytocin induction , compared with 17.5 % of those in the 72-hour group ( RR 5.8 , 95 % CI 3.9 - 8.5 ; P < .001 ) . Women undergoing induction after 72-hour expectant management had an increased risk of cesarean delivery compared with those after a 12-hour wait ( RR 5.9 , 95 % CI 2.3 - 15.1 ; P < .001 ) . Overall , women in the 12-hour group had shorter admission-to-discharge times than the 72-hour group ( 5 versus 6 days , 95 % CI of the difference 0.6 - 1.3 ; P < .01 ) . Conclusion Regimens of 12-hour and 72-hour expectant management of PROM are comparable regarding infectious complications and pregnancy outcome . However , the longer wait prolongs the interval to delivery and increases hospitalization costs OBJECTIVE We hypothesize that expectant management in the presence of premature rupture of membranes at term would result in a lower cesarean birth rate with no increase in maternal , fetal , or neonatal infection . STUDY DESIGN Term patients who consented to the study were r and omly allocated either to expectant management for 48 hours or to induction of labor 8 hours after premature rupture of membranes . Premature rupture of membranes was confirmed by sterile speculum examination of the vagina . Patients r and omized to expectant management were transferred to antenatal care and were not examined vaginally until they went into labor . Patients r and omized to induction of labor had induction with oxytocin 8 hours after premature rupture of membranes . RESULTS Two hundred sixty-two patients were r and omized to the expectant management and induction of labor groups . The cesarean birth rate and the clinical diagnosis of postpartum endometritis was not significantly different in the two groups . Pathologic diagnosis of chorioamnionitis and funisitis , however , was significantly greater in the expectant management group ( p < 0.05 ) . Eight of the 15 babies with funisitis were admitted to the neonatal intensive care unit for therapy ( two in the induction of labor group and six in the expectant management group , p < 0.05 ) . CONCLUSION Expectant management did not reduce the incidence of cesarean birth and increased the pathologic diagnosis of funisitis and newborn requirements for neonatal intensive care A prospect i ve , r and omized study was conducted comparing the use of betamethasone and early delivery , early delivery alone , and expectant management in patients in the 28th to 34th week of pregnancy with premature rupture of the membranes ( PROM ) . Tocolytic drugs were used to delay delivery until 24 hours had elapsed after the first dose of steroid or 24 to 48 hours of latent period had elapsed in the second group . There were ho significant differences in maternal age , gestation at PROM , maximum maternal temperature , birth weights , maternal hospital days , respiratory distress , maternal sepsis , or delivery routes in the three groups . Comparisons with one other similar prospect i ve , r and omized study support the concept that expectant management offers less risk from tocolytic side effects OBJECTIVE Our purpose was to compare induction of labor with preterm rupture of membranes between 34 and 37 weeks ' gestation with expectant management . STUDY DESIGN In this prospect i ve investigation 120 gravid women at > or = 34 weeks 0 days and < 36 weeks 6 days of gestation were r and omized to receive oxytocin induction ( n = 57 ) or observation ( n = 63 ) . RESULTS Estimated gestational age at rupture of membranes ( 34.3 + /- 1.4 weeks vs 34.5 + /- 1.4 weeks ) and ultrasonographically estimated fetal weight ( 2230 + /- 321 gm vs 2297 + /- 365 gm ) were equivalent between groups ( not significant ) . Chorioamnionitis occurred more often ( 16 % vs 2 % , p = 0.007 ) , and maternal hospital stay ( 5.2 + /- 6.8 days vs 2.6 + /- 1.6 days , p = 0.006 ) was significantly longer in the control group . Neonatal sepsis was also more common in the observation group ( n = 3 ) than among induction patients ( n = 0 ) , but the difference was not statistically significant . CONCLUSION Aggressive management of preterm premature rupture of the membranes at > or = 34 weeks 0 days of gestation by induction of labor is safe for the infant in our population and avoids maternal-neonatal infectious complications OBJECTIVE This study was undertaken to determine the effect of antenatal betamethasone administration on the incidences of respiratory distress syndrome , intraventricular hemorrhage , and perinatal infectious morbidity in the setting of preterm premature rupture of membranes . STUDY DESIGN We performed a nonconcurrent prospect i ve analysis of women with singleton pregnancies who were delivered between 24 and 32 weeks ' gestation after preterm premature rupture of membranes . Patients were subdivided into 2 groups according to betamethasone exposure : ( 1 ) none ( control group ) and ( 2 ) two 12-mg doses in a 24-hour interval on admission ( single-course group ) . Patients who received > 2 doses of betamethasone were excluded . All patients received broad-spectrum prophylactic antibiotics . Data were analyzed with the Student t test , the chi(2 ) test , and the Fisher exact test . Multiple logistic regression analyses incorporated multiple variables considered risk factors for respiratory distress syndrome and intraventricular hemorrhage . P < .05 for all 2-tailed tests was considered significant . RESULTS A total of 362 patients were included , with 203 in the control group and 159 in the single-course group . Patients in these groups were delivered at 31.0 + /- 3.0 and 30.2 + /- 2.7 ( mean + /- SD ) weeks ' gestation , respectively . The groups were similar with respect to selected demographic characteristics , latency until delivery , mode of delivery , birth weight , and maternal group B streptococcal colonization status . Univariate analysis demonstrated significant decreases in the frequencies of both respiratory distress syndrome ( odds ratio , 0.31 ; 95 % confidence interval , 0.2 - 0.5 ) and grade III/IV intraventricular hemorrhage ( odds ratio , 0.14 ; 95 % confidence interval , 0.1 - 0.6 ) in the single-course group . The frequencies of early neonatal sepsis , chorioamnionitis , endometritis , and neonatal death were similar between groups . Multiple logistic regression analyses determined that a single course of betamethasone was independently associated with reductions in the frequencies of both respiratory distress syndrome ( odds ratio , 0.16 ; 95 % confidence interval , 0.1 - 0.4 ) and grade III/IV intraventricular hemorrhage ( odds ratio , 0.18 ; 95 % confidence interval , 0.1 - 0.4 ) . CONCLUSIONS A single course of betamethasone administered antenatally to patients with preterm premature rupture of membranes was associated with decreases in the frequencies of both respiratory distress syndrome and advanced grade s of intraventricular hemorrhage without any increase in perinatal infectious morbidity A r and om clinical trial to compare two managements : a conservative one ( experimental group ) and an interventionist one ( control group ) in patients with PROM in pregnancy between 28 and 34 weeks , was carried out . A group of women with complicate pregnancies with PROM , with amniotic fluid index of 5 cm in four quadrants , and a negative amniotic fluid culture , by amniocenthesis ; no antibiotics , were studied at Perinatology Department , Centro Médico Nacional , IMSS , Torreón , Coah . México , from November 1 , 1992 to October 31 , 1993 . The latency period was longer in the experimental group , than the control group ( 7.9 and 3 days , p < 0.001 ) . There were no difference in chorioamnioitis or endometritis in both groups ( p > 0.1 ) . There were five cases of mid RDS in the experimental group , and seven cases in the control group , and nine of severe RDS , all of them died ; there was a highly significant difference in perinatal mortality , ( p = 0.005 ) . There were no differences in neonatal sepsis ( p > 0.05 ) . Adequate selection of patients for conservative management is safe for both , mother and newborn . Complications and death by sepsis were uncommon A prospect i ve r and omized study involving patients with premature rupture of the membranes between the twenty-eighth week and the thirty-fourth week of pregnancy was conducted . Patients with chorioamnionitis , advanced labor , and fetal distress , as well as those with mature lecithin/sphingomyelin ratios and /or Gram stains positive for bacteria , were delivered immediately . The remaining patients were r and omized . One group received betamethasone . Tocolytic agents were used in this group when necessary . After 48 hours all patients given corticosteroids ( CS group ) were delivered ) . The second group was managed expectantly ( EM group ) and were delivered only when spontaneous labor or infection occurred . A total of 160 patients were r and omized , 80 in each group . Maternal outcome , including chorioamnionitis and cesarean section rates , was not different ; however , the endometritis rate was significantly higher in the CS group ( p less than 0.05 ) . Neonatal outcome did not differ in mean birth weights , perinatal death rates , neonatal infections , or incidences of respiratory distress . The frequency of prolonged hospital stay ( greater than 4 weeks ) was higher in the neonates in the CS group ( p less than 0.01 ) . The conclusion is that corticosteroids and active management in patients with premature rupture of the membranes and premature gestations do not decrease the incidence of respiratory distress syndrome or perinatal mortality and may aggravate certain infectious complications OBJECTIVE To assess whether administration of dexamethasone in women with preterm premature rupture of membranes ( PPROM ) has an effect on the prevalence of maternal sepsis , neonatal respiratory distress syndrome ( RDS ) , perinatal mortality and neonatal sepsis in a developing country . SETTING Six public hospitals in South Africa that deal mainly with indigent women . METHOD A multicentre , double-blind , placebo-controlled , r and omised trial was performed on women with PPROM and fetuses of 28 - 34 weeks ' gestation or clinical ly estimated fetal weight between 1,000 and 2,000 g if the gestational age was unknown . Women were r and omised to receive either dexamethasone 24 mg intramuscularly or placebo in two divided doses 24 hours apart . All women received amoxycillin and metronidazole and were managed expectantly . Hexoprenaline was administered if contractions occurred within the first 24 hours after admission to the trial . OUTCOME MEASURES The maternal outcome measures were clinical chorio-amnionitis and postpartum sepsis . The outcome measures for infants were perinatal death , RDS , mechanical ventilation , necrotising enterocolitis , and neonatal infection within 72 hours . RESULTS One hundred and two women who delivered 105 babies were r and omised to the dexamethasone group and 102 women who delivered 103 babies , to the placebo group . The groups were well balanced with regard to clinical features . There was a trend towards fewer perinatal deaths in the dexamethasone group : 4 compared with 10 ( P = 0.16 , odds ratio 0.37 , 95 % confidence intervals 0.09 - 1.34 ) . A sub analysis of mothers who delivered more than 24 hours after admission to the study and their infants revealed a significant reduction in perinatal deaths ; 1 death in the dexamethasone group and 7 in the placebo group , P = 0.047 ( Fisher 's exact test ) . No woman in either group developed severe sepsis , and the incidence of sepsis in the women did not differ significantly . Eleven infants in each group developed sepsis . CONCLUSION This is the first r and omised trial in women with PPROM to compare the effects of the use of corticosteroids with placebo , where all women received prophylactic antibiotics concomitantly with the corticosteroids . A trend towards an improved perinatal outcome was demonstrated in the women who received dexamethasone . There was no increased risk of infection in the women or their infants where dexamethasone was administered . Administration of corticosteroids to women with PPROM has more advantages than disadvantages in developing countries The use of hydrocortisone and timed delivery was compared to expectant management of pregnancies complicated by preterm prematurely ruptured membranes in a prospect i ve r and omized trial of 73 patients . The incidence of maternal and neonatal complications was compared . There was no significant difference in the incidence of respiratory distress syndrome . Steroid-treated mothers had an increased incidence of postpartum febrile morbidity . We conclude that treatment of women with preterm prematurely ruptured membranes with hydrocortisone and timed delivery offers no advantage over expectant management Objective To determine maternal and neonatal outcomes in pregnancies complicated by preterm rupture of membranes ( PROM ) at 30–34 weeks ' gestation . Methods A r and omized controlled trial was conducted to study the benefits of expectant management in women hospitalized for PROM at 30–34 weeks ' gestation . During this investigation , no tocolytics , corticosteroids , or prophylactic antibiotics were used . Results Sixty-eight women with PROM were managed expectantly and 61 were delivered intentionally . The mean gestational age at study entry was 31.7 weeks in both the expectant management and intentional delivery groups ( P > .05 ) . The mean gestational ages at delivery were similar ( 32.0 and 31.7 weeks , respectively ) . Other indices of pregnancy outcome ( ie , birth weight , intraventricular hemorrhage , necrotizing enterocolitis , sepsis , respiratory distress syndrome , and perinatal death ) were not significantly improved by expectant management . However , there was a significant increase in the incidence of chorioamnionitis and antepartum hospitalization in the women managed expectantly . Conclusion There were no clinical ly significant neonatal advantages to expectant management of ruptured membranes at 30–34 weeks . Antepartum hospitalization was decreased by 2.5 days in those women r and omized to intentional delivery Background Preterm prelabour rupture of the membranes ( PPROM ) is an important clinical problem and a dilemma for the gynaecologist . On the one h and , awaiting spontaneous labour increases the probability of infectious disease for both mother and child , whereas on the other h and induction of labour leads to preterm birth with an increase in neonatal morbidity ( e.g. , respiratory distress syndrome ( RDS ) ) and a possible rise in the number of instrumental deliveries . Methods / Design We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management . Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34 + 0 weeks until 37 + 0 weeks will be included in a multicentre prospect i ve r and omised controlled trial . We will compare early delivery with expectant monitoring . The primary outcome of this study is neonatal sepsis . Secondary outcome measures are maternal morbidity ( chorioamnionitis , puerperal sepsis ) and neonatal disease , instrumental delivery rate , maternal quality of life , maternal preferences and costs . We anticipate that a reduction of neonatal infection from 7.5 % to 2.5 % after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity . Under these assumptions , we aim to r and omly allocate 520 women to two groups of 260 women each . Analysis will be by intention to treat . Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management . Long term outcomes will be evaluated using modelling . Discussion This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis . Controlled clinical trial registerIS RCT |
10,309 | 30,067,939 | Meta‐ analysis of 24 neuroimaging studies revealed consistently reported regions .
Some regions were specific to study design and task .
Patterns of regions resembled intrinsic brain networks and corticostriatal loops .
Co‐activated regions formed prefrontal‐brainstem and insula‐brainstem ensembles .
Multilevel kernel density analysis of 24 studies ( 37 statistical maps ; 264 coordinates ; 457 participants ) revealed consistent effects in the amygdala , hippocampus , hypothalamus , striatum , insula , midbrain , and brainstem , as well as prefrontal and temporal cortices .
Effects in some regions were specific to particular study design s and tasks .
Spatial pattern analysis revealed significant overlap of reported effects with limbic , default mode , ventral attention , and corticostriatal networks , and co‐activation analyses revealed functional ensembles encompassing the prefrontal cortex , insula , and midbrain/brainstem . | Abstract Communication between the brain and peripheral mediators of systemic inflammation is implicated in numerous psychological , behavioral , and physiological processes .
Functional neuroimaging studies have identified brain regions that associate with peripheral inflammation in humans , yet there are open questions about the consistency , specificity , and network characteristics of these findings .
The present systematic review provides a meta‐ analysis to address these questions . | BACKGROUND Although inflammatory activity is known to play a role in depression , no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia , a key diagnostic symptom of depression . To investigate this , we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely , reduced ventral striatum ( VS ) activity to reward cues . We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood . METHODS Participants ( n = 39 ) were r and omly assigned to receive either placebo or low-dose endotoxin , which increases proinflammatory cytokine levels in a safe manner . Cytokine levels were repeatedly assessed through hourly blood draws ; self-reported and observer-rated depressed mood were assessed regularly as well . Two hours after drug administration , neural activity was recorded as participants completed a task in which they anticipated monetary rewards . RESULTS Results demonstrated that subjects exposed to endotoxin , compared with placebo , showed greater increases in self-reported and observer-rated depressed mood over time , as well as significant reductions in VS activity to monetary reward cues . Moreover , the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward . CONCLUSIONS The data reported here show , for the first time , that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood . As such , these findings have implication s for underst and ing risk of depression in persons with underlying inflammation Although social withdrawal is a prominent symptom of sickness , the mechanisms associated with this behavioral change remain unclear . In animals , the amygdala is a key neural region involved in sickness-induced social withdrawal . Consistent with this , in humans , heightened amygdala activity to negative social cues is associated with social avoidance tendencies . Based on these findings , we investigated whether an experimental inflammatory challenge selectively increased amygdala activity to socially threatening images as well as whether this activity related to feelings of social disconnection . Thirty-nine participants were r and omly assigned to receive either placebo or low-dose endotoxin , which increases inflammatory activity . Pro-inflammatory cytokines were assessed at 7 hourly time points via blood draws ; self-reported feelings of social disconnection and physical sickness symptoms were assessed hourly as well . Two hours post-injection , participants underwent an fMRI procedure to assess amygdala reactivity during the presentation of socially threatening images ( fear faces ) as well as non-socially threatening images ( guns ) , socially non-threatening images ( happy faces ) , and non-social , non-threatening images ( household objects ) . Endotoxin led to greater amygdala activity in response to socially threatening vs. all other types of images . No such differences were found for placebo participants . Additionally , increased amygdala activity in endotoxin participants during the viewing of socially vs. non-socially threatening images was associated with increased feelings of social disconnection . These findings highlight the amygdala as a neural region that may be important for sickness-induced social withdrawal . The implication s of amygdalar involvement in sickness-induced social withdrawal are discussed Background We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation . Methods and Results Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers . In 12 subjects , dilatation of the brachial artery to flow and to sublingual nitroglycerin ( NTG ) was recorded ( conduit vessel response ) , and in 6 subjects , venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine ( ACh ) and bradykinin ( BK ) and the endothelium-independent dilators NTG and verapamil ( resistance vessel response ) . Responses were assessed 16 hours before and 8 and 32 hours after vaccination . Vaccination result ed in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist . Eight hours after vaccination , resistance vessel responses to BK ( P = 0.0099 ) and ACh ( P = 0.0414 ) were markedly attenuated , and brachial artery flow-mediated dilatation was depressed . Resistance vessel responses to verapamil and NTG were unchanged , as was the conduit vessel response to NTG . Thirty-two hours after vaccination , resistance vessel responses to BK and ACh had returned to normal . Conclusions S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli . This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event Significance Functional MRI ( fMRI ) is 25 years old , yet surprisingly its most common statistical methods have not been vali date d using real data . Here , we used resting-state fMRI data from 499 healthy controls to conduct 3 million task group analyses . Using this null data with different experimental design s , we estimate the incidence of significant results . In theory , we should find 5 % false positives ( for a significance threshold of 5 % ) , but instead we found that the most common software packages for fMRI analysis ( SPM , FSL , AFNI ) can result in false-positive rates of up to 70 % . These results question the validity of a number of fMRI studies and may have a large impact on the interpretation of weakly significant neuroimaging results . The most widely used task functional magnetic resonance imaging ( fMRI ) analyses use parametric statistical methods that depend on a variety of assumptions . In this work , we use real resting-state data and a total of 3 million r and om task group analyses to compute empirical familywise error rates for the fMRI software packages SPM , FSL , and AFNI , as well as a nonparametric permutation method . For a nominal familywise error rate of 5 % , the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference . Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape . By comparison , the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference . These findings speak to the need of validating the statistical methods being used in the field of neuroimaging Background Systemic infections commonly cause sickness symptoms including psychomotor retardation . Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain . Methods We used functional magnetic resonance brain imaging ( fMRI ) to investigate neural effects of peripheral inflammation following typhoid vaccination in 16 healthy men , using a double-blind , r and omized , crossover-controlled design . Results Vaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation . During a cognitive task , individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses . Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra . Conclusions Our findings provide mechanistic insights into the interaction between inflammation and neurocognitive performance , specifically implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection BACKGROUND Infectious , autoimmune , and neurodegenerative diseases are associated with profound psychological disturbances . Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes . However , the mechanisms underlying the respective psychological alterations in humans have not been established yet . Therefore , we investigated the effects of low-dose endotoxemia , a well-established and safe model of host-defense activation , on emotional , cognitive , immunological , and endocrine parameters . METHODS In a double-blind , crossover study , 20 healthy male volunteers completed psychological question naires and neuropsychological tests 1 , 3 , and 9 hours after intravenous injection of Salmonella abortus equi endotoxin ( 0.8 ng/kg ) or saline in 2 experimental sessions . Blood sample s were collected hourly , and rectal temperature and heart rate were monitored continuously . RESULTS Endotoxin had no effects on physical sickness symptoms , blood pressure , or heart rate . Endotoxin caused a mild increase in rectal temperature ( 0.5 degrees C ) , and increased the circulating levels of tumor necrosis factor alpha ( TNF-alpha ) , soluble TNF receptors , interleukin (IL)-6 , IL-1 receptor antagonist , and cortisol . After endotoxin administration , the subjects showed a transient significant increase in the levels of anxiety ( effect size [ ES ] = 0.55 ) and depressed mood ( ES = 0.66 ) . Verbal and nonverbal memory functions were significantly decreased ( ES = 0.55 to 0.64 ) . Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety ( r = 0.49 to r = 0.60 ) , depressed mood ( r = 0.40 to r = 0.75 ) , and decreases in memory performance ( r = 0.46 to r = 0.68 ) . CONCLUSIONS In humans , a mild stimulation of the primary host defense has negative effects on emotional and memory functions , which are probably caused by cytokine release . Hence , cytokines represent a novel target for neuropsychopharmacological research Increases in peripheral cytokines during acute inflammation may affect various neuropsychological functions . The aim of this functional magnetic resonance imaging ( fMRI ) study was to investigate the effects of acute endotoxemia on mood and the neural response to emotionally aversive visual stimuli in healthy human subjects . In a double-blind , r and omized crossover study , 18 healthy males received a bolus injection of bacterial lipopolysaccharide ( LPS ; 0.4 ng/kg ) or saline . Plasma levels of pro- and anti-inflammatory cytokines and cortisol as well as mood ratings were analyzed together with the blood-oxygen-level dependent ( BOLD ) response during the presentation of aversive versus neutral pictures . Endotoxin administration induced pronounced transient increases in plasma levels of TNF-α , IL-1ra , IL-6 , IL-10 , and cortisol . Positive mood was decreased and state anxiety increased . In addition , activation of right inferior orbitofrontal cortex ( OFC ) in response to emotional visual stimuli was significantly increased in the LPS condition . Increased prefrontal activation during the presentation of emotional material may reflect enhanced cognitive regulation of emotions as an adaptive response during an acute inflammation . These findings may have implication s for the putative role of inflammatory processes in the pathophysiology of depression Significance The periaqueductal gray is a brainstem region that is critical for autonomic regulation and for defensive responses ( e.g. , “ fight , ” “ flight , ” “ freeze ” ) . It has been studied extensively in rodents and cats , but less is known about the human periaqueductal gray . The small size and shape of the periaqueductal gray makes it challenging to study using st and ard noninvasive MRI techniques . We used a high-field strength magnet to examine this region at high resolution while participants viewed emotionally aversive or neutral images . Emotion-related functional activity was concentrated in particular subregions and in ways that are consistent with neurobiological observations in nonhuman animals . This study establishes a technique to uncover the functional architecture of the periaqueductal gray in humans . The midbrain periaqueductal gray ( PAG ) region is organized into distinct subregions that coordinate survival-related responses during threat and stress [ B and ler R , Keay KA , Floyd N , Price J ( 2000 ) Brain Res 53 (1):95–104 ] . To examine PAG function in humans , research ers have relied primarily on functional MRI ( fMRI ) , but technological and method ological limitations have prevented research ers from localizing responses to different PAG subregions . We used high-field strength ( 7-T ) fMRI techniques to image the PAG at high resolution ( 0.75 mm isotropic ) , which was critical for dissociating the PAG from the greater signal variability in the aqueduct . Activation while participants were exposed to emotionally aversive images segregated into subregions of the PAG along both dorsal/ventral and rostral/caudal axes . In the rostral PAG , activity was localized to lateral and dorsomedial subregions . In caudal PAG , activity was localized to the ventrolateral region . This shifting pattern of activity from dorsal to ventral PAG along the rostrocaudal axis mirrors structural and functional neurobiological observations in nonhuman animals . Activity in lateral and ventrolateral subregions also grouped with distinct emotional experiences ( e.g. , anger and sadness ) in a factor analysis , suggesting that each subregion participates in distinct functional circuitry . This study establishes the use of high-field strength fMRI as a promising technique for revealing the functional architecture of the PAG . The techniques developed here also may be extended to investigate the functional roles of other brainstem nuclei 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 Interferon-alpha ( IFN-α ) is a key mediator of antiviral immune responses used clinical ly for hepatitis C treatment . Though effective , IFN-α induces marked behavioral changes that , when severe , can appear indistinguishable from major depression . Curiously , fatigue and motivational impairment evolve rapidly , suggesting acute engagement of immune-brain communicatory pathways , yet mood impairments typically emerge later , after weeks of treatment . Whether this reflects prolonged modulation of motivational processes underpinning fatigue or separate neurobiological mechanisms is currently unclear . Methods Here , we used quantitative magnetization transfer ( qMT ) imaging , an advanced microstructural neuroimaging technique sensitive to effects of inflammation , in a prospect i ve study design to measure acute brain changes to IFN-α and relate these to later development of discrete behavioral changes . Twenty-three patients initiating IFN-α treatment for hepatitis C underwent qMT imaging and blood sampling at baseline and 4 hours after their first IFN-α injection . Comprehensive behavioral and psychological assessment s were completed at both scanning sessions and at treatment weeks 4 , 8 , 12 , and 24 . Results IFN-α injection stimulated an acute inflammatory cytokine response and evoked fatigue that peaked between 4 and 12 weeks , preceding mood change by 4 weeks . In the brain , IFN-α induced an acute change in striatal microstructure that additionally predicted development of fatigue but not mood symptoms . Conclusions Our findings highlight qMT as an in vivo biomarker of central effects of peripheral inflammation . We demonstrate exquisite sensitivity of the striatum to IFN-α , implicate striatal perturbation in IFN-α-induced fatigue , and dissociate this from mechanisms underlying IFN-α-induced mood symptoms , providing empirical support for distinct neural substrates mediating actions on motivation and mood Background Inflammatory cytokines are implicated in the pathophysiology of depression . In rodents , systemically administered inflammatory cytokines induce depression-like behavior . Similarly in humans , therapeutic interferon-α induces clinical depression in a third of patients . Conversely , patients with depression also show elevated pro-inflammatory cytokines . Objectives To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing . Methods In a double-blind , r and omized crossover study , 16 healthy male volunteers received typhoid vaccination or saline ( placebo ) injection in two experimental sessions . Mood question naires were completed at baseline and at 2 and 3 hours . Two hours after injection , participants performed an implicit emotional face perception task during functional magnetic resonance imaging . Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression . Results Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours . Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex ( sACC ) ( a region implicated in the etiology of depression ) during emotional face processing . Furthermore , inflammation-associated mood change reduced connectivity of sACC to amygdala , medial prefrontal cortex , nucleus accumbens , and superior temporal sulcus , which was modulated by peripheral interleukin-6 . Conclusions Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli . Peripheral cytokines modulate this mood-dependent sACC connectivity , suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression Task-based fMRI has been used to study the effects of experimental inflammation on the human brain , but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response . Here , we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states , motivation , and subjective symptoms of sickness . In a double-blind r and omized controlled experiment , 52 healthy volunteers were injected with 0.6ng/kg LPS ( lipopolysaccharide ) or placebo , and participated in a resting state fMRI experiment after approximately 2h 45min . Resting state fMRI data were available from 48 participants , of which 28 received LPS and 20 received placebo . Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate ( anterior and middle ) cortices was investigated . Back pain , headache and global sickness increased significantly after as compared to before LPS , while a non-significant trend was shown for increased nausea . Compared to placebo , LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex . This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness , but was not related to increased headache or nausea . LPS did not affect the connectivity from other insular seeds . In conclusion , the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to underst and the subjective feeling of malaise and discomfort during a sickness response Acute peripheral inflammation with corresponding increases in peripheral cytokines affects neuropsychological functions and induces depression-like symptoms . However , possible effects of increased immune responses on social cognition remain unknown . Therefore , this study investigated the effects of experimentally induced acute inflammation on performance and neural responses during a social cognition task assessing Theory of Mind ( ToM ) ability . In this double-blind r and omized crossover functional magnetic resonance imaging study , 18 healthy right-h and ed male volunteers received an injection of bacterial lipopolysaccharide ( LPS ; 0.4 ng/kg ) or saline , respectively . Plasma levels of pro- and anti-inflammatory cytokines as well as mood ratings were analyzed together with brain activation during a vali date d ToM task ( i.e. Reading the Mind in the Eyes Test ) . LPS administration induced pronounced transient increases in pro- ( IL-6 , TNF-α ) and anti-inflammatory ( IL-10 , IL-1ra ) cytokines as well as decreases in mood . Social cognition performance was not affected by acute inflammation . However , altered neural activity was observed during the ToM task after LPS administration , reflected by increased responses in the fusiform gyrus , temporo-parietal junction , superior temporal gyrus and precuneus . The increased task-related neural responses in the LPS condition may reflect a compensatory strategy or a greater social cognitive processing as a function of sickness Although stress-induced increases in inflammation have been implicated in several major disorders , including cardiovascular disease and depression , the neurocognitive pathways that underlie inflammatory responses to stress remain largely unknown . To examine these processes , we recruited 124 healthy young adult participants to complete a laboratory-based social stressor while markers of inflammatory activity were obtained from oral fluids . A subset of participants ( n = 31 ) later completed an fMRI session in which their neural responses to social rejection were assessed . As predicted , exposure to the laboratory-based social stressor was associated with significant increases in two markers of inflammatory activity , namely a soluble receptor for tumor necrosis factor-α ( sTNFαRII ) and interleukin-6 ( IL-6 ) . In the neuroimaging sub sample , greater increases in sTNFαRII ( but not IL-6 ) were associated with greater activity in the dorsal anterior cingulate cortex and anterior insula , brain regions that have previously been associated with processing rejection-related distress and negative affect . These data thus eluci date a neurocognitive pathway that may be involved in potentiated inflammatory responses to acute social stress . As such , they have implication s for underst and ing how social stressors may promote susceptibility to diseases with an inflammatory component Background Inflammation is associated with psychological , emotional , and behavioral disturbance , known as sickness behavior . Inflammatory cytokines are implicated in coordinating this central motivational reorientation accompanying peripheral immunologic responses to pathogens . Studies in rodents suggest an afferent interoceptive neural mechanism , although comparable data in humans are lacking . Methods In a double-blind , r and omized crossover study , 16 healthy male volunteers received typhoid vaccination or saline ( placebo ) injection in two experimental sessions . Profile of Mood State question naires were completed at baseline and at 2 and 3 hours . Two hours after injection , participants performed a high-dem and color word Stroop task during functional magnetic resonance imaging . Blood sample s were performed at baseline and immediately after scanning . Results Typhoid but not placebo injection produced a robust inflammatory response indexed by increased circulating interleukin-6 accompanied by a significant increase in fatigue , confusion , and impaired concentration at 3 hours . Performance of the Stroop task under inflammation activated brain regions encoding representations of internal bodily state . Spatial and temporal characteristics of this response are consistent with interoceptive information flow via afferent autonomic fibers . During performance of this task , activity within interoceptive brain regions also predicted individual differences in inflammation-associated but not placebo-associated fatigue and confusion . Maintenance of cognitive performance , despite inflammation-associated fatigue , led to recruitment of additional prefrontal cortical regions . Conclusions These findings suggest that peripheral infection selectively influences central nervous system function to generate core symptoms of sickness and reorient basic motivational states BACKGROUND There has been increasing interest in the role of immunologic processes , notably cytokines , in the development of behavioral alterations , especially in medically ill patients . Interferon (IFN)-alpha is notorious for causing behavioral symptoms , including depression , fatigue , and cognitive dysfunction , and has been used to investigate the effects of cytokines on the brain . METHODS In the present study we assessed the effects of low-dose IFN-alpha on brain activity , using functional magnetic resonance imaging during a task of visuospatial attention in patients infected with hepatitis C virus ( HCV ) . RESULTS Despite endorsing symptoms of impaired concentration and fatigue , IFN-alpha-treated patients ( n = 10 ) exhibited task performance and activation of parietal and occipital brain regions similar to that seen in HCV-infected control subjects ( n = 11 ) . Interestingly , however , in contrast to control subjects , IFN-alpha-treated patients exhibited significant activation in the dorsal part of the anterior cingulate cortex ( ACC ) , which highly correlated with the number of task-related errors . No such correlation was found in control subjects . CONCLUSIONS Consistent with the role of the ACC in conflict monitoring , ACC activation during IFN-alpha administration suggests that cytokines might increase processing conflict or reduce the threshold for conflict detection , thereby signaling the need to exert greater mental effort to maintain performance . Such alterations in ACC activity might in turn contribute to cytokine-induced behavioral changes Background Asthma is a chronic inflammatory disease noteworthy for its vulnerability to stress and emotion-induced symptom intensification . The fact that psychological stress and mood and anxiety disorders appear to increase expression of asthma symptoms suggests that neural signaling between the brain and lung at least partially modulates the inflammatory response and lung function . However , the precise nature of the neural pathways implicated in modulating asthma symptoms is unknown . Moreover , the extent to which variations in neural signaling predict different phenotypes of disease expression has not been studied . Methods and Results We used functional magnetic resonance imaging to measure neural signals in response to asthma-specific emotional cues , following allergen exposure , in asthmatics with a dual response to allergen challenge ( significant inflammation ) , asthmatics with only an immediate response ( minimal inflammation ) , and healthy controls . The anterior insular cortex was differentially activated by asthma-relevant cues , compared to general negative cues , during the development of the late phase of the dual response in asthmatics . Moreover , the degree of this differential activation predicted changes in airway inflammation . Conclusions These findings indicate that neurophenotypes for asthma may be identifiable by neural reactivity of brain circuits known to be involved in processing emotional information . Those with greater activation in the anterior insula , in response to asthma-relevant psychological stimuli , exhibit greater inflammatory signals in the lung and increased severity of disease and may reflect a subset of asthmatics most vulnerable to the development of psychopathology . This approach offers an entirely new target for potential therapeutic intervention in asthma |
10,310 | 32,242,117 | Risk factors for GORD were also identified which may allow clinicians to recognise individuals most at risk | Although gastro-oesophageal reflux disease ( GORD ) is a common medical complaint , there is currently no consensus on the global prevalence of GORD .
The aim of this study was to conduct a systematic review and meta- analysis on GORD prevalence and risk factors at a global level . | Objective . Gastroesophageal reflux disease has been reported to be a common burden on health-care re sources in the Western world , but its manifestations in the general population are as yet unclear . The aim of this study was to estimate the prevalence of , and to identify the risk factors for gastroesophageal reflux symptoms ( GERS ) and erosive esophagitis ( EE ) in the adult population of two Swedish municipalities . Material and methods . A r and om sample ( n=3000 ) of the adult population ( 20–81 years of age ) of two Swedish municipalities ( n=21,610 ) was surveyed using a vali date d postal question naire assessing gastrointestinal symptoms . The response rate was 74 % . A sub sample ( n=1000 ) of the responders was subsequently invited , in r and om order , for esophago-gastro-duodenoscopy with evaluation of GERS , risk factors and tests for Helicobacter pylori . Results . GERS were reported by 40.0 % and EE was found in 15.5 % of the population that had undergone endoscopy . Of those with GERS , 24.5 % had EE while 36.8 % of those with EE reported no GERS . Hiatus hernia and obesity remained significant risk factors for GERS and /or EE , with or without symptoms in a main effect model ( OR up to 14 at EE ) . Those with active H. pylori infection had a higher risk of GERS without EE than those without H. pylori infection ( OR=1.71 ( 1.23–2.38 ) ) . Conclusions . GERS and EE ( of which one-third is asymptomatic ) are highly prevalent in the Swedish adult population . H. pylori infection seems to play a role in the manifestations of gastroesophageal reflux BACKGROUND & AIMS Gastroesophageal reflux is considered a common condition , but detailed population -based data on reflux in the United States are lacking . The aim of this study was to determine the prevalence and clinical spectrum of gastroesophageal reflux in Olmsted County , Minnesota . METHODS A reliable and valid self-report question naire was mailed to an age- and sex-stratified r and om sample of 2200 Olmsted County residents aged 25 - 74 years . RESULTS The prevalence per 100 of heartburn and /or acid regurgitation experienced at least weekly was 19.8 ( 95 % confidence interval [ 95 % CI ] , 17.7 - 21.9 ) . Heartburn and acid regurgitation were associated with noncardiac chest pain ( odds ratio [ OR ] , 4.2 ; 95 % CI , 2.9 - 6.0 ) , dysphagia ( OR , 4.7 ; 95 % CI , 2.9 - 7.4 ) , dyspepsia ( OR , 3.1 ; 95 % CI , 1.9 - 5.0 ) , and globus sensation ( OR , 1.9 ; 95 % CI , 1.0 - 3.6 ) but not with asthma , hoarseness , bronchitis , or a history of pneumonia . Among subjects with reflux symptoms , 1.0 % reported an episode of hematemesis and 1.3 % had a past esophageal dilatation . CONCLUSIONS Symptoms of reflux are common among white men and women who are 25 - 74 years of age . Heartburn and acid regurgitation are significantly associated with chest pain , dysphagia , dyspepsia , and globus sensation . The percentage of patients reporting complications is low , but the absolute number is probably considerable given the high prevalence of the condition in the community AIM To clarify the association between physical activity and gastroesophageal reflux disease ( GERD ) in non-obese and obese people . METHODS A Swedish population -based cross-sectional survey was conducted . Participants aged 40 - 79 years were r and omly selected from the Swedish Registry of the Total Population . Data on physical activity , GERD , body mass index ( BMI ) and the covariates age , gender , comorbidity , education , sleeping problems , and tobacco smoking were obtained using vali date d question naires . GERD was self-reported and defined as heartburn or regurgitation at least once weekly , and having at least moderate problems from such symptoms . Frequency of physical activity was categorized into three groups : ( 1 ) " high " ( several times/week ) ; ( 2 ) " intermediate " ( approximately once weekly ) ; and ( 3 ) " low " ( 1 - 3 times/mo or less ) . Analyses were stratified for participants with " normal weight " ( BMI < 25 kg/m² ) , " overweight " ( BMI 25 to ≤ 30 kg/m² ) and " obese " ( BMI > 30 kg/m² ) . Multivariate logistic regression was used to calculate odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) , adjusted for potential confounding by covariates . RESULTS Of 6969 eligible and r and omly selected individuals , 4910 ( 70.5 % ) participated . High frequency of physical activity was reported by 2463 ( 50 % ) participants , GERD was identified in 472 ( 10 % ) participants , and obesity was found in 680 ( 14 % ) . There were 226 ( 5 % ) individuals with missing information about BMI . Normal weight , overweight and obese participants were similar regarding distribution of gender and tobacco smoking status , while obese participants were on average slightly older , had fewer years of education , more comorbidity , slightly more sleeping problems , lower frequency of physical activity , and higher occurrence of GERD . Among the 2146 normal-weight participants , crude point estimates indicated a decreased risk of GERD among individuals with high frequency of physical activity ( OR : 0.59 , 95 % CI : 0.39 - 0.89 ) , compared to low frequency of physical activity . However , after adjustment for potential confounding factors , neither intermediate ( OR : 1.30 , 95 % CI : 0.75 - 2.26 ) nor high ( OR : 0.99 , 95 % CI : 0.62 - 1.60 ) frequency of physical activity was followed by decreased risk of GERD . Sleeping problems and high comorbidity were identified as potential confounders . Among the 1859 overweight participants , crude point estimates indicated no increased or decreased risk of GERD among individuals with intermediate or high frequency of physical activity , compared to low frequency . After adjustment for confounding , neither intermediate ( OR : 0.75 , 95 % CI : 0.46 - 1.22 ) nor high frequency of physical activity were followed by increased or decreased risk of GERD compared to low frequency among nonobese participants . Sleeping problems and high comorbidity were identified as potential confounders for overweight participants . In obese individuals , crude ORs were similar to the adjusted ORs and no particular confounding factors were identified . Intermediate frequency of physical activity was associated with a decreased occurrence of GERD compared to low frequency of physical activity ( adjusted OR : 0.41 , 95 % CI : 0.22 - 0.77 ) . CONCLUSION Intermediate frequency of physical activity might decrease the risk of GERD among obese individuals , while no influence of physical activity on GERD was found in non-obese people Objective : Prostagl and ins regulate gastric motor function . Inhibition of prostagl and ins by nonsteroidal antiinflammatory drugs ( NSAIDs ) may alter gastric emptying . To study gastric emptying of solids and its relation to endoscopic findings and Helicobacter pylori in patients receiving long-term NSAIDs , we undertook this study . Methods : Ninety-five patients with arthritis , 65 taking long-term NSAIDs ( Group I ) and 30 not taking NSAIDs ( Group II ) were studied . Presence of dyspeptic symptoms was determined using a question naire . Mucosal damage was determined by endoscopy . H. pylori was detected by antral biopsies for rapid urease test and histology . Gastric emptying for solids was evaluated using a scintigraphic method . Thirty healthy volunteers were used as controls for gastric emptying ( Group III ) . Patients with peptic ulcer were excluded from the analysis of gastric emptying . Logistic regression analysis was performed to identify predictive factors for gastric emptying . Results : Nineteen patients from Group I with peptic ulcers were excluded . Dyspeptic symptoms were seen in 24 ( 52 % ) Group I and seven ( 23 % ) Group II patients . Gastroduodenal erosions were seen in 10 ( 21.7 % ) Group I patients and four ( 13.3 % ) Group II patients . H. pylori was detected in 17 patients in Group I ( 36.9 % ) and Group II ( 56.6 % ) . Gastric emptying was delayed in 24 ( 52 % ) Group I patients , six ( 20 % ) Group II patients ( p < 0.001 ) , and in none of the Group III controls . The mean gastric emptying times were 99.5 ( 15.6 ) min and 89 ( 17.7 ) min for Groups I and II , respectively ( p < 0.05 ) . Endoscopic damage was found with similar frequency in Group I patients with delayed or normal gastric emptying . H. pylori infection was present in 37.5 % Group I patients with delayed gastric emptying and in 36.3 % with normal gastric emptying ( p= ns ) . Logistic regression analysis identified NSAID therapy as the single factor most predictive of delayed gastric emptying . Conclusion : Delayed gastric emptying was seen in 52 % of patients on long-term NSAID therapy Background : Although the ingestion of chilli has been associated with gastroesophageal reflux ( GER ) symptoms , there are no studies that have explored the effect of a chronic ingestion of different kinds of chilli with a variable content of capsaicin as a cause of GER . Methods : The effect of chilli on esophageal 24-hour pH monitoring was studied in 12 healthy subjects without GER symptoms before and after of ingestion one of two kinds of chilli . Patients were r and omized to ingest 3 g daily of cascabel chilli ( Capsicum annum coraciforme containing 880 ppmof capsaicin ) or ancho chilli ( Capsicum annum grossum containing 488 ppm of capsaicin ) . Results : After chilli ingestion , the Johnson De Meester Index ( JDI ) increased significantly [ basal : 7 ( 1–14 ) , after chilli : 13 ( 2–69 ) , p = 0.0047 ] . When considering both kinds of chilli separately , the JDI varied , although nonsignificantly , with the ancho chilli [ basal : 3 ( 1–8 ) , after chilli : 10 ( 2–69 ) , p = 0.11 ] , and significantly with the cascabel chilli [ basal : 10 ( 5–14 ) , after chilli : 18 ( 2–44 ) , p = 0.028 ] . Conclusion : Our results suggest that the chronic ingestion of chilli induces GER , and that the magnitude of the induced reflux seems to be related to the kind of chilli BACKGROUND Two types of reflux episodes have been identified : upright or daytime and supine or nocturnal . The population -based prevalence of symptoms of nocturnal gastroesophageal reflux disease ( GERD ) and the impact of those symptoms on health-related quality of life ( HRQL ) have not been established . METHODS A national r and om- sample telephone survey was conducted to estimate the prevalence of frequent GERD and nocturnal GERD-like symptoms and to assess the relationship between HRQL , GERD , and nocturnal GERD symptoms . Respondents were classified as controls , subjects with symptomatic nonnocturnal GERD , and subjects with symptomatic nocturnal GERD . The HRQL was assessed using the Medical Outcomes Study Short-Form 36 Health Survey ( SF-36 ) . RESULTS The prevalence of frequent GERD was 14 % , with an overall prevalence of nocturnal GERD of 10 % . Seventy-four percent of those with frequent GERD symptoms reported nocturnal GERD symptoms . Subjects with nonnocturnal GERD had significant decrements on the SF-36 physical and mental component summary scores compared with the US general population . Subjects reporting nocturnal GERD symptoms were significantly more impaired than subjects reporting nonnocturnal GERD symptoms on both the physical component summary ( 38.94 vs 41 . 52 ; P<.001 ) and mental component summary ( 46.78 vs 49.51 ; P<.001 ) and all 8 subscales of the SF-36 ( P<.001 ) . Subjects with nocturnal GERD demonstrated considerable impairment compared with the US general population and chronic disease population s. Subjects with nocturnal GERD had significantly more pain than those with hypertension and diabetes ( P<.001 ) and similar pain compared with those with angina and congestive heart failure . CONCLUSIONS Nocturnal symptoms are commonly experienced by individuals who report frequent GERD symptoms . In addition , HRQL is significantly impaired in those persons who report frequent GERD symptoms , and HRQL impairment is exacerbated in those who report nocturnal GERD symptoms Symptoms suggestive of gastro-oesophageal reflux disease are very common . The aim of the study was to assess the prevalence of these symptoms and factors influencing them in an unselected adult population . A question naire was mailed to a r and om sample of 2500 people aged > or = 20 years . The questions concerned heartburn , regurgitation , dysphagia , chest and upper abdominal pain , as well as medication and medical consultations for these symptoms . Of the 1700 ( 68 % ) responders , 9 % had experienced heartburn on the day of response and 15 % , 21 % and 27 % during the preceding week , month and year , respectively . The corresponding figures for regurgitation were 5 , 15 , 29 and 45 % . During the past year 43 % of the study group had had no such symptoms . Age , overweight , pregnancy and cigarette smoking significantly influenced the prevalence of symptoms . Using daily heartburn and /or regurgitation as dominant indicators 10.3 % ( 95 % CI 12 - 11.7 ) of the responders had gastro-oesophageal reflux disease . Medication ( most commonly antacids ) was used by only 16 % of the symptomatic people , and only 5.5 % had sought medical advice for symptoms during the past year . Thus , despite commonness of symptoms suggestive of gastro-oesophageal reflux disease only a minority of the individuals suffering from such symptoms use medication or have medical consultation BACKGROUND The prevalence of gastroesophageal reflux disease ( GERD ) in Asian population s is reported to be lower than that in the West . Population -based data on the prevalence and symptom profile of GERD in developing Caucasian countries is lacking . Our objective was to determine the prevalence of gastrointestinal symptoms and clinical spectrum of GERD in Tehran , northern Iran and their association with patient characteristics . METHODS One thous and seven hundred telephone numbers were r and omly selected from Tehran telephone directory using a simple r and om method . A two-step screening telephone survey was then performed . In each answered call a second rapid survey was done to select a subject 18 - 65 years old from that household . A vali date d question naire was then filled out for that individual . Patient characteristics ( age , education , and gender ) and history of acid regurgitation and heartburn during the last week , as well as the previous three months were inquired about . RESULTS Of the 1,700 selected numbers , 278 either did not answer or did not have an eligible case ; 220 refused to participate . A total of 1,202 subjects ( 42 % males , mean age : 36 years , range : 18 - 65 yr ) were surveyed . The prevalence of heartburn occurring monthly , weekly , and daily was 4.7 % ( CI95 % : 3.5 - 6.0 % ) , 1.6 % ( CI95 % : 1.0 - 2.5 % ) , and 0.6 % ( CI95 % : 0.3 - 1.3 % ) , respectively . The corresponding figures for acid regurgitation were 15.6 % ( CI95 % : 13.6 - 17.7 % ) , 5.7 % ( CI95 % : 4.4 - 7.1 % ) and 1.5 % ( CI95 % : 0.9 - 2.4 % ) , respectively . The prevalence of GERD , defined as heartburn and /or acid regurgitation experienced daily , weekly and monthly was 1.9 % ( CI95 % : 1.2 - 2.9 % ) , 6.8 % ( CI95 % : 5.4 - 8.3 % ) , and 18.4 % ( CI95 % : 16.2 - 20.6 % ) . There was no relationship between the prevalence of GERD and either gender , age , or education . CONCLUSION Monthly GERD symptoms occur in 18.4 % of the general population in Tehran . Acid regurgitation is more common ( 4 - 5 times ) than heartburn . Gender , age , and level of education do not affect the prevalence of GERD symptoms in the community studied Background Predictors of erosive esophagitis ( EE ) and Barrett ’s esophagus ( BE ) and the influence of number of risk factors in the community are not well defined . Methods Rates of BE and EE among community residents identified in a r and omized screening trial were defined . The risk of EE and BE associated with single and multiple risk factors ( gender , age , GERD , Caucasian ethnicity , ever tobacco use , excess alcohol use , family history of BE or EAC , and central obesity ) was analyzed . Results Sixty-eight ( 33 % ) of 205 subjects had EE and /or BE . BE prevalence was 7.8 % with dysplasia present in 1.5 % . Rates were comparable between subjects with and without GERD . Male sex and central obesity were independent risk factors . The odds of EE or BE were 3.7 times higher in subjects with three or four risk factors and 5.7 times higher in subjects with five or more risk factors compared with those with two or less factors . Conclusions EE and BE are prevalent in the community regardless of the presence of GERD . Risk appeared to be additive , increasing substantially with three or more risk factors Background We aim ed to determine the prevalence of gastroesophageal reflux disease ( GERD ) and associated risk factors , and assess quality of life ( QoL ) in relation to the frequency and severity of reflux symptoms . Methods A r and om sample of 1000 residents of Western Sydney were mailed a vali date d self-report question naire . GERD symptoms , risk factors , psychologic distress , QoL , and demographics were measured . Results The response rate was 73 % ( n=672 ; mean age , 46 y ; 52 % female ) . A total of 78 [ 12 % , 95 % confidence interval ( CI ) : 9 - 14 ] had GERD ( at least weekly heartburn and /or acid regurgitation ) . Independent risk factors for GERD were high cholesterol [ odds ratio ( OR ) = 3.28 , 95 % CI : 1.42 - 7.57 , P=0.005 ] and current smoker ( OR=2.47 , 95 % CI : 1.07 - 5.70 , P=0.03 ) . Anxiety , depression , and neuroticism were not risk factors . Worse physical functioning was the only QoL domain associated with GERD ( OR=0.98 , 95 % CI : 0.97 - 0.99 , P=0.006 ) . QoL was significantly impaired regardless of the severity of GERD for the QoL domains physical function , body pain , vitality , and social function . The frequency of heartburn and acid regurgitation were not associated with significantly reduced QoL domain scores . Conclusions Cardiac risk factors ( high cholesterol and smoking ) were independently associated with GERD . Increasing GERD symptom severity is associated with worse QoL scores , whereas GERD symptom frequency did not impact the QoL scores Many people with gastro-esophageal reflux symptoms do not consult a physician ; therefore studies on gastro-esophageal reflux in general practice or in hospitals may not accurately describe the burden of gastro-esophageal reflux symptoms in the general population . The aim of this study was to assess the prevalence of gastro-esophageal reflux disease and its association with some life-style parameters in Rasht-Iran . A telephone survey was performed . Phone numbers was r and omly collected from the telecommunication service center of Rasht . 1473 people ( Mean age : 38.31 ± 13.09 ) were included in the study . People who did n't answer the phone after three times or did n't have consent to enter the study were excluded . Data were collected by an examiner using a GerdQ question naire . The validity and reliability of the question naire was tested by translation and retranslation and a pilot study was performed to assess its appropriateness . The prevalence of gastro-esophageal reflux was achieved 2.4 % daily , 9.1 % weekly and 11.3 % monthly . Among the patients with gastro-esophageal reflux , 69.5 % were female . There was a significant positive association between gastro-esophageal reflux prevalence and body mass index , smoking habits , eating salted or smoked foods , lying down immediately after the meal , taking certain drugs as non-steroidal anti-inflammatory drugs/Amino salicylic acid and the age group of 30 - 45 year old . Overall , the prevalence of the weekly gastro-esophageal reflux in the present survey was 9.1 % which was less than other similar studies in Iran and some other countries AIM To evaluate the prevalence of gastroesophageal reflux disease ( GERD ) with additional symptoms , relationship with Helicobacter pylori ( H. pylori ) of this country-wide study . METHODS Data from 3214 adults were obtained with vali date d question naire . Eight hundred and forty-one subjects were r and omized to be tested for H. pylori via the urea breath test . " Frequent symptoms " were defined heartburn and /or regurgitation occurring at least weekly . RESULTS The prevalence of GERD was 22.8 % , frequent and occasional heartburn were 9.3%-12.7 % , regurgitation were 16.6%-18.7 % , respectively . Body mass index ( BMI ) ≤ 18.5 showed a prevalence of 15 % , BMI > 30 was 28.5 % . The GERD prevalence was higher in women ( 26.2 % ) than men ( 18.9 % ) ( P < 0001 ) . Overall prevalence of H. pylori was 75.7 % . The prevalence was 77.1 % in subjects without symptoms vs 71.4 % in subjects with GERD ( χ2 = 2.6 , P = 0.27 ) . Underprivileged with the lowest income people exhibit a higher risk . CONCLUSION GERD is common in Turkey which reflects both Western and Eastern lifestyles with high rate of H. pylori . The presence of H. pylori had no effect on either the prevalence or the symptom profile of GERD . Subjects showing classical symptoms occasionally exhibit more additional symptoms compared with those without classical symptoms BACKGROUND Gastroesophageal reflux disease ( GERD ) is one of the most common gastrointestinal problems worldwide . The aim of this study was to evaluate the clinical spectrum , prevalence , and some of the variables that are supposed to be the risk factors of this chronic disorder . METHODS This population - based cross-sectional study was conducted in a one-stage r and omized clustered sample of adult inhabitants in Kerman city in 2011 - 2012 . A total of 2265 subjects with age range of 15 - 85 years were enrolled . Face to face interview was performed for all the subjects . GERD was defined as at least weekly heart burn and /or acid regurgitation during the past year . Association of GERD with factors like demographic variables , medical condition , diet and life habits were analyzed . RESULTS A total of 2265 subjects including 988 ( 43.8 % ) male and 1275 ( 56.3 % ) female patients were evaluated . The prevalence of GERD was 28 % . The prevalence was higher in female patients and with aging . There was also a significant association between GERD and the following risk factors : lower educational level ( p < 0.0001 ) , higher body mass index ( p = 003 ) , presence of depression(p<0.0001 ) , and anxiety ( p < 0=0001 ) . CONCLUSION GERD as a common disorder in our region was seen more in elderly and female patients and was associated with some anthropometric , metabolic , medical conditions , and behavioral habits Aim . We aim ed to assess the prevalence and lifestyle correlates of gastroesophageal reflux disease ( GERD ) in the adult population of Albania , a Mediterranean country in Southeast Europe which has experienced major behavioral changes in the past two decades . Methods . A cross-sectional study , conducted in 2012 , included a population -representative sample of 845 individuals ( ≥18 years ) residing in Tirana ( 345 men , mean age : 51.3 ± 18.5 ; 500 women , mean age : 49.7 ± 18.8 ; response rate : 84.5 % ) . Assessment of GERD was based on Montreal definition . Covariates included socioeconomic characteristics , lifestyle factors , and body mass index . Logistic regression was used to assess the association of socioeconomic characteristics and lifestyle factors with GERD . Results . The overall prevalence of GERD was 11.9 % . There were no significant sex differences , but a higher prevalence among the older participants . In fully adjusted models , there was a positive relationship of GERD with smoking , physical inactivity , fried food consumption , and obesity , but not so for alcohol intake and meat consumption . Conclusion . We obtained important evidence on the prevalence and lifestyle correlates of GERD in a Western Balkans ' country . Smoking , physical inactivity , and obesity were strong “ predictors ” of GERD in this population . Findings from this study should be replicated in prospect i ve studies in Albania and other transitional setting BACKGROUND This paper reports the 3-month prevalence rates of gastrointestinal ( GI ) symptoms from the Domestic/International Gastroenterology Surveillance Study ( DIGEST ) , and their relationship with demographic factors ; namely age , gender and body mass index ( BMI ) . METHODS Subjects were recruited from 10 international sites by a total of 5581 face-to-face interviews conducted with r and omly selected members of the general population aged 18 years and over ( 50.6 % female ; mean age 44 years ) . The sample was divided according to whether subjects reported 1 or more of 14 GI symptoms , or no GI symptoms . Those with any of 11 upper GI symptoms were then subdivided according to their most bothersome symptom : gastro-oesophageal reflux (GORD)-like symptoms , ulcer-like symptoms or dysmotility-like symptoms . Symptoms were classified as relevant if they were of at least moderate severity and /or occurred at least once a week . RESULTS A mean of 46.4 % of subjects reported experiencing one or more of the 14 GI symptoms , with 28.1 % experiencing upper GI symptoms classified as relevant . Significant differences between the prevalences of relevant symptoms were evident between sampling sites . The estimated prevalence of GORD-like symptoms for the pooled sample was 7.7 % . For ulcer-like symptoms , prevalence was 4.1 % , and for dysmotility-like symptoms 15.5 % . Significant differences were observed in the prevalence rates of symptom groups between countries . Women were significantly more likely than men to experience relevant symptoms , with gender differences also observed in the rates of GORD-like and dysmotility-like symptoms . The proportion of those with relevant symptoms experiencing GORD-like symptoms increased significantly with age ; ulcer-like symptoms showed no significant relationship with age ; and dysmotility-like symptoms decreased significantly with age . The prevalence of relevant symptoms increased with increasing BMI . CONCLUSIONS In conclusion , the DIGEST has provided valuable data on the cross-country prevalence of upper GI symptoms , and their association with biological factors Background —The current classification dividing patients with functional gastrointestinal symptoms into subgroups remains controversial . Aims —To determine whether distinct symptom groupings exist in the community . Methods —A r and om sample of Sydney residents in Penrith , Australia was mailed a vali date d self report question naire . Gastrointestinal symptoms including the Rome criteria for irritable bowel syndrome ( IBS ) and dyspepsia were measured . Results —Among 730 respondents , the 12 month age and gender adjusted prevalence ( adjusted to the Australian population ) of IBS , dyspepsia , and gastro-oesophageal reflux were 11.8 % ( 95 % confidence interval ( CI ) 9.3 to 14.3 % ) , 11.5 % ( 95 % CI 9.6 to 14.6 % ) , and 17.5 % ( 95 % CI 14.2 to 19.9 % ) , respectively . In total , 60 % of the population reported four or more gastrointestinal symptoms . There was considerable overlap of IBS with dyspepsia and among the dyspepsia subgroups by application of the Rome criteria . Independently , 10 symptom groupings were identified by factor analysis . The underlying constructs measured by these factors were generally the major abdominal syndromes recognised by the Rome classification : dyspepsia , IBS , reflux , painless constipation , painless diarrhoea , and bloating , in addition to a number of more specific symptom groupings . Conclusion —Gastrointestinal symptoms are common and overlap in the community , but distinct upper and lower abdominal symptom groupings can be identified Dysphagia is an alarming symptom that raises the possibility of stricture or malignancy . This study compares the prevalence and severity of dysphagia symptoms in subjects with or without gastroesophageal reflux ( GERD ) . In a population -based study , 500 residents of Cologne between the ages of 20 and 90 years [ 232 ( 46 % ) males and 268 ( 54 % ) females ] were r and omly selected from the city register and sent question naires with reflux-related questions . Two hundred sixty-eight replies ( 54 % ) were accepted into the study . Of these , 45 % were men with a median age of 58 years . The median female age was 54 years . Thirty-four percent of the respondents ( n = 92 ) admitted having heartburn symptoms . There was no significant gender-based difference . There was little variation in reflux frequency between individual age groups . Twenty-three ( 25 % ) of the 92 respondents with reflux reported symptoms more than twice per week . Forty-five percent of this “ reflux ” group took medications for their heartburn . Swallowing difficulties , predominantly mild , were reported in 11.3 % of the respondents . Dysphagia was significantly increased in the reflux group ( 28 % ) versus the normal group ( 3 % ) ( p < 0.001 ) . Sixteen percent of respondents with mild and 65 % of those with moderate to severe reflux symptoms reported additional dysphagia symptoms ( p < 0.001 ) . Swallowing problems are common in patients with GERD . Approximately two thirds of patients with long-term and severe reflux symptoms also have dysphagia symptoms . Dysphagia should always be investigated by a physician Objective There are few data on the epidemiology of gastroesophageal reflux disease ( GERD ) in South China . The aim of this study was to assess the prevalence of GERD symptoms in South China and to evaluate the impact on health-related quality of life . Material and methods A face-to-face interview was carried out in South China using a vali date d Chinese version of the Reflux Disease Question naire to assess the prevalence of GERD symptoms . A r and omly clustered sampling of permanent inhabitants aged 18 to 90 years was carried out under stratification of urban and suburban areas . The impact of GERD symptoms on health-related quality of life was evaluated using the Chinese version of SF-36 . Results A total of 3338 residents ( 1468 M , 1870 F ) were investigated . Mean age of the responders was 42.6±16.4 years ; response rate was 95 % . The prevalence of heartburn and /or acid eructation occurring at least weekly was 6.2 % . The age- and gender-adjusted point prevalence of GERD symptoms in South China is 2.3 % ( 95 % CI , 1.8 % , 2.8 % ) according to the definition in this study . There was no difference in prevalence between male ( 2.6 % ) and female ( 2.4 % ) subjects and there was no significant association between age and prevalence of GERD symptoms . Divorced/widowed/separated subjects ( OR 4.61 ; 95 % CI , 2.15 % , 9.89 % ) and subjects with a heavy burden of work ( OR 3.43 , 95 % CI , 1.72 % , 6.84 % ) were significantly more likely to report GERD symptoms . As compared with the general population , subjects with GERD symptoms experienced considerable impairment in quality of life . Conclusions The prevalence of GERD symptoms in South China was much lower than that reported in Western countries . GERD had a negative impact on quality of life BACKGROUND / AIMS Dyspepsia and gastroesophageal reflux disease are common chronic diseases . In the clinical setting , some patients express both problems together ; however , little is known about the real prevalence of the presence of the two symptoms . Turkey is particularly interesting because of differences observed from developed countries . We aim ed to derive data from our previous prevalence of gastroesophageal reflux disease study and evaluate the overlap of the two symptoms . METHODS We used a previously vali date d and culturally adapted reflux question naire , which was translated into Turkish . The question naire was applied to 630 r and omly selected subjects older than 20 years living in a population of 8857 adults . RESULTS 28.6 % ( 180/630 ) of all responders defined dyspepsia within the last 12-month period . When symptom prevalence was considered at least weekly , the prevalence was 10 % for heartburn , 15.6 % for acid regurgitation , and 20 % for either symptom . While the prevalence of gastroesophageal reflux disease was 29.4 % in patients with dyspepsia , dyspepsia was found in 43.1 % of patients with gastroesophageal reflux disease . Only 21 % of symptomatic subjects or 8.4 % of the entire study population had both symptoms . Dyspepsia was defined as the most bothersome symptom . 54.3 % of all dyspeptic patients and 67.3 % with both gastroesophageal reflux disease and dyspepsia used a gastric medication ( p>0.05 ) . 29.9 % of subjects with dyspeptic symptoms defined antacid consumption and 28.3 % acid inhibitor therapy . CONCLUSION Dyspepsia was defined as the most bothersome symptom compared to gastroesophageal reflux disease symptoms . The prevalence of dyspepsia in patients with gastroesophageal reflux disease is more common than vice versa . However , the overlap of the two symptom groups was lower than expected in this low-income , Caucasian population BACKGROUND AND STUDY AIMS Gastro-oesophageal reflux disease ( GERD ) and dyspepsia are common digestive disorders that inflict serious harm , burden and economic consequences on individuals worldwide . The aim of this study was to estimate the direct and indirect economic burden of GERD and dyspepsia in the whole population of Tehran , the capital of Iran . PATIENTS AND METHODS The study was performed on a total of 18,180 adult subjects ( age>18 years ) taken as a r and om sample in Tehran province , Iran ( 2006 - 2007 ) . A valid and reliable question naire was used to enquire about the symptoms of GERD , dyspepsia and the frequency of the utilization of health services including physician visits , hospitalisations and productivity loss due to GERD/dyspepsia symptoms in the preceding 6 months . RESULTS GERD was found in 518 ( 41.9 % males ) patients and dyspepsia in 404 patients ( 38.9 % males ) . Further 1007 subjects had both GERD and dyspepsia . The total direct costs of disease per patient for GERD , dyspepsia and their overlap were PPP$97.70 , PPP$108.10 and PPP$101.30 , respectively ( PPP , purchasing power parity dollars ) . The total indirect cost of disease per patient was PPP$13.7 , PPP$12.1 and PPP$32.7 , for GERD , dyspepsia and their overlap , respectively . CONCLUSION According to our results , hospitalisation and physician visits were the main cost of disease that could be minimised by revision of the insurance business in Iran BACKGROUND few studies have reported the onset and disappearance rates of gastroesophageal reflux symptoms ( GERS ) in the population . AIM to assess the occurrence and disappearance rates of GERS in Spain , and their impact on health-related quality of life ( HRQL ) . PARTICIPANTS AND METHODS participants were selected at r and om from the general population of Madrid in age and sex strata . They were interviewed at home twice , 6 months apart . Heartburn , acid regurgitation and consultation were assessed with the gastroesophageal reflux question naire , and HRQL with the SF-36 . RESULTS 709 individuals were included , and 451 ( 63.6 % ) were re-interviewed 6 months later . Among the 325 individuals without GERS , 9 developed weekly symptoms ( 2.2 % [ 95 % CI : 0.8 , 3.4 % ] ) ; 2 ( 22 % ) consulted because of GERS . Among the 34 subjects reporting weekly GERS initially , 26 did not report them at 6-months . Onset of GERS was associated with worsening scores in the physical summary of SF-36 ( delta = -6.6 [ 95 % CI : -11.8 , -1.42 ] ) , while disappearance with an improved score ( delta = -3.0 [ 95 % CI : 0.0 , 5.9 ] ) . CONCLUSION despite the lower prevalence of GERS in Spain , the occurrence rate is 2.2 % in 6 months ; however symptoms disappeared in more than half of subjects six months later . Developing GERS was associated with reduced HRQL , and their disappearance with improvement Background Gastroesophageal reflux disease ( GERD ) is a common chronic gastrointestinal tract disease . The incidence is higher in Asian and Arab countries . In Saudi Arabia , there are few studies that have assessed the prevalence of GERD among some cities ' communities . Hence , this study aims to study the prevalence of GERD among the general population of Saudi Arabia . Methods A cross-sectional study was design ed to determine the prevalence of GERD among the community of Saudi Arabia . The sample was r and omly gathered through self-administered vali date d GERD question naire ( GerdQ ) to diagnose GERD , during the period from November to December 2016 . The sociodemographic data was assessed for all participants . The data were analysed using Statistical Package for Social Sciences version 21.0 ( SPSS ) ; the t-test was used to assess the association of GERD and sociodemographic data . Results The sample was comprised of 2,043 participants . Female and male were 51.8 % and 48.2 % , respectively . Mean age was 29.6 years with the st and ard deviation of 10.5 years . The GERD prevalence was 28.7 % . It was found statistically significant among divorced/widow ( 34.9 % , P = 0.003 ) . In contrast , there was no association between GERD 's prevalence and gender , age , residence status , education level , occupation , and blood group ( P > 0.05 ) . Conclusions The prevalence of GERD among Saudi population is higher than that in Western countries and East Asia . It affects divorced/widow , obese and those with a sedentary lifestyle . It is advocated that national programs and educational campaigns for prevention of this disease and its complications should be established Background : Population ‐based data on gastro‐oesophageal reflux disease in Chinese are lacking . The prevalence , clinical spectrum and health care‐seeking behaviour of subjects with gastro‐oesophageal reflux disease were studied Background Gastroesophageal reflux disease ( GERD ) and its complications are thought to be infrequent in India ; there are no data from India on the prevalence of and risk factors for GERD . The Indian Society of Gastroenterology formed a task force aim ing to study : ( a ) the frequency and profile of GERD in India , ( b ) factors including diet associated with GERD . Methods In this prospect i ve , multi-center ( 12 centers ) study , data were obtained using a question naire from 3224 subjects regarding the frequency , severity and duration of heartburn , regurgitation and other symptoms of GERD . Data were also obtained regarding their dietary habits , addictions , and lifestyle , and whether any of these were related or had been altered because of symptoms . Data were analyzed using univariate and multivariate methods . Results Two hundred and forty-five ( 7.6 % ) of 3224 subjects had heartburn and /or regurgitation at least once a week . On univariate analysis , older age ( OR 1.012 ; 95 % CI 1.003–1.021 ) , consumption of non-vegetarian and fried foods , aerated drinks , tea/coffee were associated with GERD . Frequency of smoking was similar among subjects with or without GERD . Body mass index ( BMI ) was similar in subjects with and without GERD . On multivariate analysis , consumption of non-vegetarian food was independently associated with GERD symptoms . Overlap with symptoms of irritable bowel syndrome was not uncommon ; 21 % reported difficulty in passage of stool and 9 % had mucus in stools . About 25 % of patients had consulted a doctor previously for their gastrointestinal symptoms . Conclusion 7.6 % of Indian subjects have significant GERD symptoms . Consumption of non-vegetarian foods was an independent predictor of GERD . BMI was comparable among subjects with or without GERD Objective Changes in the occurrence of gastro-oesophageal reflux symptoms ( GORS ) in the population remain uncertain . This study aim ed to determine the prevalence changes , the incidence and the spontaneous loss of GORS . Design This population -based cohort study was conducted within the Nord-Trøndelag Health Study ( the HUNT study ) , a longitudinal series of population -based health surveys in Nord-Trøndelag County , Norway . The study base encompassed all adult residents in the county , and the participants reported the degree of GORS during the previous 12 months . The number of participants included were 58 869 ( 64 % response rate ) in 1995–7 and 44 997 ( 49 % ) in 2006–9 . Of these , 29 610 persons ( 61 % ) were prospect ively followed up for an average of 11 years . Results Between 1995–7 and 2006–9 , the prevalence of any , severe and at least weekly GORS increased by 30 % ( from 31.4 % to 40.9 % ) , 24 % ( from 5.4 % to 6.7 % ) and 47 % ( from 11.6 % to 17.1 % ) , respectively . The average annual incidence of any and severe GORS was 3.07 % and 0.23 % , respectively . In women , but not men , the incidence of GORS increased with increasing age . The average annual spontaneous loss ( not due to antireflux medication ) of any and severe GORS was 2.32 % and 1.22 % , respectively . The spontaneous loss of GORS decreased with increasing age . Conclusion Between 1995–7 and 2006–9 the prevalence of GORS increased substantially . At least weekly GORS increased by 47 % . The average annual incidence of severe GORS was 0.23 % , and the corresponding spontaneous loss was 1.22 % . The incidence and spontaneous loss of GORS were influenced by sex and age AIM To investigate the prevalence and risk factors of gastroesophageal reflux disease ( GERD ) symptoms in Qashqai migrating nomads with a different life style in Fars province , southern Iran . METHODS In summer 2006 , 748 Qashqai migrating nomads aged 25 years or more were enrolled using a multiple-stage stratified cluster r and om sampling method . A question naire consisting of demographic characteristics , lifestyle and GERD symptoms ( heartburn , regurgitation , chest pain , dysphagia , hoarseness and cough ) as completed for each subject . RESULTS The question naire was completed in 717 subjects . The prevalence rate of GERD , defined as reflux occurring at least one time per week in the preceding year , was 33 % ( 237 subjects ) . The prevalence was higher in older individuals ( 36.0 % vs 28.9 % , P < 0.05 ) and in those with other gastrointestinal complaints ( 51.0 % vs 27.8 % , P < 0.001 ) , but not different in obese and non-obese subjects . It was also higher in those consuming fruits and vegetables more than once a week ( 36.2 % vs 17.3 % , P < 0.001 ) . GERD had a positive correlation with smoking ( 42.1 % vs 27.8 % , P < 0.001 ) , but a negative relation with non-alcoholic beverages . The association between GERD and non-steroidal anti-inflammatory drugs ( NSAIDs ) consumption was also significant ( 40.2 % vs 25.4 % , P < 0.001 ) . CONCLUSION The prevalence of GERD ( 33 % ) is very high in Qashqai migrating nomads which may be due to a lower socioeconomic and educational level of these people and difference in the life style . Older age , frequent consumption of fruits and vegetables , smoking and NSAIDs are risk factors for GERD in this population AIMS To describe the prevalence and severity of dyspepsia and gastro-oesophageal reflux in the community , to investigate their association with lifestyle factors and to evaluate the consultation pattern for these conditions . METHOD A previously vali date d question naire was posted to 1000 adults r and omly selected from the electoral rolls of the greater Wellington region . It investigated symptoms of dyspepsia , reflux , lifestyle and consultation pattern over the previous twelve months . RESULTS Response rate was 81.7 % . Prevalence of dyspepsia was 34.2 % . Prevalence of reflux was 30 % . The overall prevalence of both symptom groups combined was 45.2 % . Most subjects had multiple symptoms . Results indicated 63 % of subjects with reflux also had symptoms of dyspepsia and 56 % of subjects with dyspepsia showed symptoms of reflux . Although 69 % of subjects with heartburn used over-the-counter medications , only 17 % consulted medical practitioners . Current and ex-smokers had a higher prevalence of reflux . Dyspeptic symptoms were not associated with alcohol intake or aspirin use . Prevalence of dyspeptic symptoms did not change with increasing age . CONCLUSIONS Dyspepsia is very common in the community . Significant overlap among the subgroups of dyspepsia makes a classification , based on symptoms alone , of question able value . Frequency and severity of symptoms should be incorporated in the definition to exclude those subjects with trivial symptoms AIM To evaluate the prevalence of chronic gastrointestinal symptoms and their impact on health-related quality of life ( HRQOL ) in the Korean population . METHODS A cross-sectional survey , using a reliable and valid Rome II based question naire , was performed on r and omly selected residents , between 18 and 69 years in age . All respondents were interviewed at their homes or offices by a team of interviewers . The impact of chronic gastrointestinal symptoms on HRQOL was assessed using the Korean version of the 36-item Short-Form general health survey ( SF-36 ) . RESULTS Of the 1807 eligible subjects , 1417 ( 78.4 % : male 762 ; female 655 ) were surveyed . Out of the respondents , 18.6 % exhibited at least one chronic gastrointestinal symptom . The prevalence of gastroesophageal reflux disease ( GERD ) , defined as heartburn and /or acid regurgitation experienced at least weekly , was 3.5 % ( 95 % CI , 2.6 - 4.5 ) . The prevalence of uninvestigated dyspepsia , irritable bowel syndrome ( IBS ) and chronic constipation based on Rome II criteria were 11.7 % ( 95 % CI , 10.1 - 13.5 ) , 2.2 % ( 95 % CI , 1.5 - 3.1 ) , and 2.6 % ( 95 % CI , 1.8 - 3.5 ) respectively . Compared with subjects without chronic gastrointestinal symptoms ( n=1153 ) , those with GERD ( n=50 ) , uninvestigated dyspepsia ( n=166 ) and IBS ( n=31 ) had significantly worse scores on most domains of the SF-36 scales . CONCLUSION The prevalence of GERD , uninvestigated dyspepsia and IBS were 3.5 % , 11.7 % and 2.2 % respectively , in the Korean population . The health-related quality of life was significantly impaired in subjects with GERD , uninvestigated dyspepsia and IBS in this community OBJECTIVE : Population -based data on gastroesophageal reflux disease ( GERD ) in Iran are limited . Current study is going to determine the prevalence of GERD in Tehran , Iran , and its association with potential risk factors . METHODS : In this cross-sectional study , a r and om clustered sample of Tehran province permanent households was selected from the latest postcodes . Data were collected by direct interview for each person aged 18–65 yr . GERD was defined as the existence of at least weekly episodes of heartburn and /or acid regurgitation during the last 6 months . All participants were asked about past and recent sanitary conditions , oral hygiene , and smoking . Odds ratios and 95 % confidence intervals ( CI ) were calculated using multivariable analysis . RESULTS : Interview was performed with 2,561 eligible subjects ( 42.3 % men ) . Response rate was 84.8 % . The prevalence of GERD was 21.2 % ( 95 % CI 18.7–23.7 ) . According to multivariable logistic regression analyses , individuals whose drinking water was obtained from well or tank during childhood were more prone to experience GERD symptoms ( OR 1.54 , 95 % CI 1.03–1.77 and OR 2.46 , 95 % CI 1.53–3.96 , respectively ) . We also detected significant associations with increasing number of missing teeth ( P value for linear trend = 0.02 ) and history of unpurified water consumption during past 10 yr ( P < 0.001 ) . Current smokers had a higher prevalence of reflux ( OR 1.82 , 95 % CI 1.32–2.51 ) . CONCLUSION : The prevalence of GERD in our Iranian population was considerably higher than that reported from other Asian studies approaching western figures . GERD prevalence was significantly associated with the history of unpurified water consumption , poor sanitary conditions of childhood , number of missing teeth , and smoking in this population Abstract Objective . Gastroesophageal reflux disease ( GERD ) is thought to be less prevalent in China than in Western countries . However , essential population -based endoscopy data are lacking for this country . Material and methods . As part of a wider study , 3600 individuals selected r and omly from the Shanghai region were asked to undergo endoscopy . Participants completed a general information question naire and a Chinese version of the Reflux Disease Question naire . When sufficient numbers were available , associations were assessed using multiple logistic regression or the Wilcoxon rank-sum test . Results . Of 3153 ( 87.6 % ) individuals who completed the survey , 1030 ( 32.7 % ) agreed to endoscopy and 1029 endoscopies were suitable for analysis . Symptom-defined GERD was more prevalent in the endoscopy group ( 4.7 % ) than in the non-endoscopy group ( 1.7 % ) . Prevalence estimates were 6.4 % for reflux esophagitis , 1.8 % for endoscopically suspected esophageal metaplasia and 0.7 % for hiatus hernia . Reflux esophagitis was more prevalent in patients with symptom-defined GERD than in those without ( 12.5 % [ 6/48 ] vs. 6.1 % [ 60/981 ] ) , and was significantly associated with reflux symptoms of any frequency or severity ( OR = 2.10 , 95 % CI 1.13–3.89 ) and with negative Helicobacter pylori infection ( OR = 0.44 , 95 % CI 0.25–0.80 ) . Only 28.8 % of participants with reflux esophagitis had heartburn and /or regurgitation symptoms . Epigastric burning was significantly more severe and frequent in participants with reflux esophagitis than in those without ( p = 0.05 ) . Conclusions . Reflux esophagitis is less prevalent in China than reported in Western countries . Further work is needed to establish why reflux esophagitis appears less symptomatic in China than in Western countries OBJECTIVE To examine the relationship between body mass and gastro-oesophageal reflux in a large population -representative sample from the UK . DESIGN AND SETTING Cross-sectional population -based study , as part of a r and omized controlled trial of eradication of Helicobacter pylori infection , in Southwest Engl and . Subjects In all , 10 537 subjects , aged 20 - 59 years , were recruited from seven general practice s. Subjects provided data on frequency and severity of dyspeptic symptoms and anthropometric measurements were taken . MAIN OUTCOME MEASURE Relationship between overweight ( body mass index [ BMI ] > /=25 kg/m(2 ) and < /=30 kg/m(2 ) ) or obesity ( BMI > 30 kg/m(2 ) ) and frequency and severity of heartburn and acid regurgitation . RESULTS Body mass index was strongly positively related to the frequency of symptoms of gastro-oesophageal reflux . The adjusted odds ratios ( OR ) for frequency of heartburn and acid regurgitation occurring at least once a week in overweight participants compared with those of normal weight were 1.82 ( 95 % CI : 1.33 - 2.50 ) and 1.50 ( 95 % CI : 1.13 - 1.99 ) respectively . Corresponding OR ( 95 % CI ) relating to obese patients were 2.91 ( 95 % CI : 2.07 - 4.08 ) and 2.23 ( 95 % CI : 1.44 - 3.45 ) respectively . The OR for moderate to severe reflux symptoms were raised in overweight and obese subjects but not to the same extent as frequency of symptoms and only the relationship between obesity and severity of heartburn reached conventional statistical significance : OR = 1.19 ; 95 % CI : 1.07 - 1.33 . CONCLUSIONS Being above normal weight substantially increases the likelihood of suffering from heartburn and acid regurgitation and obese people are almost three times as likely to experience these symptoms as those of normal weight BACKGROUND Although patients with gastroesophageal reflux are often instructed to change their lifestyle , population -based data on the risk factors for reflux in the United States are lacking . METHODS We performed a cross-sectional study in an age- and gender-stratified r and om sample of the population of Olmsted County , Minnesota . Residents aged 25 to 74 years were mailed a valid self-report question naire that measured reflux symptoms and potential risk factors . Logistic regression was used to estimate the odds ratios ( OR ) with 95 % confidence intervals ( CI ) for reflux symptoms ( heartburn or acid regurgitation ) associated with potential risk factors . RESULTS Overall , 1,524 ( 72 % ) of 2,118 eligible subjects responded . A body mass index > 30 kg/m2 ( OR = 2.8 ; CI , 1.7 to 4.5 ) , reporting an immediate family member with heartburn or disease of the esophagus or stomach ( OR = 2.6 ; CI , 1.8 to 3.7 ) , a past history of smoking ( OR = 1.6 ; CI , 1.1 to 2.3 ) , consuming more than seven drinks per week ( OR = 1.9 ; Cl , 1.1 to 3.3 ) , and a higher psychosomatic symptom checklist score ( OR per 5 units = 1.4 ; CI , 1.3 to 1.6 ) were independently associated with frequent ( at least weekly ) reflux symptoms . CONCLUSION Obesity is a strong risk factor for gastroesophageal reflux , although the value of weight reduction remains to be proven . That family history was also a risk factor suggests that there may be a genetic component to the disorder BACKGROUND AND AIM Although reflux esophagitis is believed to be common in the Western population , very few epidemiologic data on reflux esophagitis in Koreans are available . The aims of this study were to evaluate the prevalence of endoscopic reflux esophagitis in patients who came for a physical check-up at Korea University Hospital , and to study the relationship between various factors relevant to reflux disease . METHODS This study was carried out prospect ively on 7,015 patients who received an esophagogastroduodenoscopy from September 1996 to December 1997 . Most of the patients were free of symptoms and had come for their self-paid check-up . RESULTS The overall prevalence of reflux esophagitis was 3.4 % , and most of the patients had a mild degree of esophagitis representing grade 1 in 98.3 % and grade 2 in 1.7 % . The male : female ratio for esophagitis was 7 : 1 , and the body mass index ( BMI ) was significantly higher in patients with reflux esophagitis . A hiatal hernia was found in 166 patients with esophagitis ( 68.6 % ) , but only in 9.2 % patients without esophagitis ( P < 0.05 ) . Smoking and alcohol consumption were associated with the development of reflux esophagitis ( P < 0.05 ) . CONCLUSIONS The prevalence of endoscopic reflux esophagitis among Koreans is 3.4 % , and most of the patients had a mild grade esophagitis . Smoking , alcohol consumption , the presence of a hiatal hernia and a higher BMI are associated with the development of reflux esophagitis OBJECTIVES : There is limited information on the relationship between gastroesophageal reflux symptoms and well-being in the general population . This study aim ed to investigate this relationship and determine the severity threshold at which reflux symptoms meaningfully affect patients ' well-being . METHODS : A r and om sample of the population of Malmö , Sweden ( n=4,624 ) , was sent the Gastrointestinal Symptom Rating Scale , the Subjective Symptom Assessment Profile , and the Psychological General Well-Being Index . The relationship between well-being and the severity of heartburn , acid regurgitation , stomach pain , and abdominal pain was investigated by analysis of covariance ( ANCOVA ) . RESULTS : Complete data were obtained from 1,476 subjects ( 43 % male ; mean age [ st and ard deviation ] , 49.9 [ 14.2 ] yr ) . The mean Psychological General Well-Being Index score was 102 ( 95 % CI : 101–103 ) . Increasing symptom severity was associated with a decrease in well-being , and correlations between Psychological General Well-Being Index score and symptom severity ratings were statistically significant . At least mild symptoms of heartburn or abdominal pain ( a mean Gastrointestinal Symptom Rating Scale score of ≥3 ) were associated with a clinical ly meaningful reduction in well-being ( a Psychological General Well-Being Index score of less than 98 ) . CONCLUSIONS : Reflux symptoms are associated with impaired well-being in the general population . Individuals with symptoms that are mild or more severe report a meaningful reduction in well-being similar to that seen in other diseases . This may represent an appropriate threshold for patient selection in trials of GERD therapy and for more detailed evaluation of patients consulting with reflux symptoms in clinical practice BACKGROUND AND AIM Epidemiological studies have indicated an increase in the prevalence of gastroesophageal reflux disease in Western countries ; however , there is a lack of information about its prevalence in Iran . The aim of this study was to measure gastroesophageal reflux disease prevalence in a representative sample of the Tehran population in 1999 . METHODS In a cross-sectional study , 700 people , with a male : female ratio of 1:1 , were selected by stratified r and omization based on the probability of 20 % prevalence of gastroesophageal reflux disease and 3 % error . They were divided equally into seven age groups . Heartburn and acid regurgitation were considered as the most common symptoms of gastroesophageal reflux disease . The severity and frequency of heartburn and the role of personal habits in the appearance of this symptom were determined . The prevalence of gastroesophageal reflux disease in sample s was measured , and its actual prevalence in society was estimated . RESULTS Of 700 people , 350 were male and 350 were female . The major symptoms of gastroesophageal reflux disease were observed in 278 ( 39.7 % ) people . The prevalence of gastroesophageal reflux disease of smokers was twice that of non-smokers . CONCLUSIONS Gastroesophageal reflux disease is a serious and unresolved problem in Western countries , and its increasing prevalence correlates with an increasing prevalence of adenocarcinoma of distal esophagus . The prevalence of gastroesophageal reflux disease appears to be increasing in Iran also ; therefore , it is recommended that major attention be paid to this disease Background / Aims : In this study , we aim ed to determine the prevalence of gastroesophageal reflux disease ( GERD ) in the general population of the capital city of Riyadh and to assess its association with other factors including age , smoking , body mass index ( BMI ) , asthma , as well as the presence of other co-morbid diseases . Material s and Methods : We used the Gastroesophageal Reflux Disease Question naire ( GerdQ ) for diagnosing GERD , based on a GerdQ score of 8 or more . Riyadh was divided into four quadrants , and from each area , a single shopping mall was chosen r and omly to conduct our surveys . Data collected included age , sex , history of smoking , history of asthma or any other medical condition , dietary habits , monthly household income , history and frequency of heartburn , epigastric pain , regurgitation of food , nausea , sleep disturbance from heartburn , the use of common over-the-counter antacids for the control of their symptoms , and their height and weight . Results : Over a 4-week period from the 19 December 2012 to 17 January 2013 , a total of 1265 individuals were included in the survey . The mean age was 29.97 ± 11.58 years . Females formed 67.81 % of the respondents and 62.73 % had one or more episodes of heartburn per week . Based on a cutoff GERDQ score of 8 , the prevalence of GERD in the surveyed population was 45.4 % . GERD was more prevalent in older individuals ( mean age 31.9 vs. 30.0 years , P < 0.001 ) and in those with a higher BMI ( 27.29 vs. 26.31 kg/m2 , P = 0.02 ) . There was no difference between males ( 45.43 % ) and females ( 45.13 % ) ( P = 0.92 ) ; there was a trend of a higher prevalence in smokers ( 51.63 % vs. 44.41 % ) , but it did not reach statistical significance ( P = 0.09 ) . Conclusion : Symptoms suggestive of GERD as determined by the translated GerdQ are prevalent among this study population Despite a common disorder population -based data on gastro-esophageal reflux disease ( GERD ) in Bangladesh is lacking . This epidemiological study was design ed to determine the prevalence of GERD and its association with lifestyle factors . This population -based cross-sectional study was done by door to door interview of r and omly selected persons in both urban and rural areas of North Eastern part of Bangladesh by using a vali date d question naire . A cutoff point 3 was chosen as a valid and reliable scale to confirm GERD . Statistical analysis was done by SPSS-12 version and the level of significance was set at P < or = 0.05 . A total of 2000 persons with an age range of 15 to 85 years were interviewed ; 1000 subjects from urban area and 1000 from rural area . Among the study subjects 1064 were male and 936 were female . A total of 110 persons ( 5.5 % ) were found to have GERD symptoms and among them 47 were men and 67 were women . The monthly , weekly and daily prevalence of heart-burn and or acid regurgitation was 5.5 % , 5.25 % and 2.5 % respectively . Female sex , increased age and lower level of education were significantly associated with GERD symptoms . Prevalence was found more among city dwellers ( approximately 6.0 % versus 4.8 % ) , married ( 6.23 % , n = 86 ) , widowed/widowers ( 16.83 % , n = 17 ) and day labourer ( 8.78 % ) . Level of education inversely influenced the prevalence . No significant association of GERD was found with body mass index ( BMI ) and smoking . Prevalence of GERD in North-Eastern part of Bangladesh was lower than that of western world . Prevalence was found higher in urban population , women , married , widowed/widowers and in poor an dilliterate persons . BMI and smoking had no significant association with GERD Background / Aims : People may have symptoms of multiple disorders at the same time . We aim ed to determine prevalence and risk factors for overlaps between gastroesophageal reflux disease ( GERD ) , dyspepsia and irritable bowel syndrome ( IBS ) in a Korean population . Methods : A cross-sectional survey was performed on 1,688 r and omly selected Korean subjects . Data on 1,443 subjects could be analyzed . Dyspepsia and IBS were diagnosed using modified Rome II criteria . Results : The prevalences of GERD , dyspepsia and IBS were 8.5 , 9.5 and 9.6 % . Overlaps between GERD and dyspepsia , GERD and IBS , and dyspepsia and IBS were observed in 2.3 ( 95 % CI 1.4–3.0 ) , 2.0 ( 95 % CI 1.2–2.6 % ) and 1.3 % ( 95 % CI 0.6–1.8 % ) of the population . 27 and 24 % of GERD subjects suffered from dyspepsia and IBS . 24 and 14 % of dyspeptic subjects had GERD and IBS . 21 and 14 % of IBS subjects had GERD and dyspepsia . Anxiety was significantly associated with GERD overlap ( OR 2.73 , 95 % CI 1.13–6.57 ) , dyspepsia overlap ( OR 3.19 , 95 % CI 1.33–7.63 ) and IBS overlap ( OR 4.92 , 95 % CI 2.04–11.84 ) , compared with GERD alone , dyspepsia alone and IBS alone . Conclusions : Overlaps between GERD , dyspepsia , and IBS are common in the general population . These overlaps occur predominantly in individuals with anxiety BACKGROUND / AIMS Epidemiological data of gastroesophageal reflux disease from Turkey is scarce . For this reason , we aim ed to determine the gastroesophageal reflux disease prevalence in our region and to compare it with both the Western part of Turkey and with other countries in the world . MATERIAL AND METHODS We used a previously vali date d reflux question naire and applied it to a r and om sample of 1345 subjects stratified by socio-economic status , who were older than 20 years and were living in the city center of Sivas . The question naire was conducted by medical students who were attending Public Health internship . RESULTS We estimated a prevalence rate of 19.3 % for gastroesophageal reflux disease , defined as heartburn and /or acid regurgitation at least once a week or more frequent . We found a significant association of gastroesophageal reflux disease with age , obesity , lying down within two hours after meals , and being under stress within the last one year , but not with smoking . Comorbid diseases associated with gastroesophageal reflux disease presence included recurrent pharyngitis , chronic cough , asthma , diabetes mellitus , hypertension , and chronic obstructive pulmonary disease , but not coronary heart disease . 50.8 % of our subjects had visited a physician for gastroesophageal reflux disease symptoms . The most common drug they used was proton pump inhibitors . CONCLUSION The prevalence of gastroesophageal reflux disease in a city of the Middle Anatolian region of Turkey was similar to that in developed countries and also to the results of another study performed in the Western part of Turkey . Further studies are needed to eluci date the role of environmental factors in the development of gastroesophageal reflux disease Abstract Introduction . Gastroesophageal reflux disease ( GERD ) , functional dyspepsia ( FD ) and irritable bowel syndrome ( IBS ) are common functional gastrointestinal conditions with significant impact on the daily lives of individuals . The objective was to investigate the prevalence and overlap of the three conditions in a Western general population . Material and methods . A nationwide study of 100,000 individuals 20 years and above , r and omly selected in the general population . A web-based question naire survey formed the basis of this study . Questions regarding FD and IBS were extracted from the ROME III adult question naire . Questions regarding GERD were developed based on the Montreal definition . Prevalence estimates for GERD , FD IBS were calculated in total and for each sex separately and for four age groups . A Venn diagram was constructed , illustrating the overlap between the three conditions . Results . The overall response rate was 52.2 % . The prevalence of GERD , FD and IBS was 11.2 % , 7.7 % and 10.5 % , respectively , and overlap between two or three of these conditions was seen among 6.5 % of the respondents . Among individuals meeting the criteria of one or more of the conditions GERD , FD and IBS , 30.7 % had overlap between two or all three conditions . Conclusion . GERD , FD and IBS are common conditions in the general population and the overlap between these conditions is also quite common . When diagnosing patients with GERD , FD and IBS , physicians should keep in mind that these patients could be suffering from more than one of these conditions We aim ed to determine the prevalence and clinical spectrum of GERD in the urban population of 6 cities in different parts of Russia ( St. Petersburg , Ryazan , Kazan , Kemerovo , Krasnoyarsk and Saransk ) . A previously vali date d reflux question naire developed at the Mayo Clinic was translated into Russian , culturally adapted and administered . Data was collected from 7812 r and omly selected subjects greater than 18 years old with the assistance of the yellow pages . ' Frequent symptoms ' were defined as a major symptom ( heartburn and /or regurgitation ) occurring at least once a week or more . " Occasional symptoms " were defined as an episode of one of the major symptoms occurring less than once a week within the past 12 months . Patients were defined as having GERD if they reported frequent heartburn and /or regurgitation . The average prevalence of frequent and occasional GERD symptoms in Russia was 9 % and 38.5 % for heartburn and 7.6 % and 35.3 % for regurgitation respectively within the last 12 months . The average prevalence of GERD in Russia was 13.3 % ( 11.3 - 14.3 % ) . The prevalence of frequent heartburn decreased with age ( r = -0.3 ) ; however , frequent regurgitation increased ( r = 0.7 ) with age . As a result , we found that prevalence of GERD increased with age . The average prevalence of GERD was statistically the same in men ( 12.5 % ) and in women ( 13.9 % ) . This prevalence did n't change with age in men but did increase with age in elderly women to 24 % . Frequent heartburn and regurgitation ( GERD ) were significantly associated with frequent belching ( 24.3 % ) , chronic cough ( 22.9 % ) , dyspepsia ( 19.8 % ) , non-cardiac chest pain ( 15.1 % ) , nausea ( 14.9 % ) , hoarseness ( 11.4 % ) , dysphagia ( 8.1 % ) , odynophagia ( 7.3 % ) and constipation ( 37.8 % ) . Alcohol consumption ( prevalence of 60.4 % among respondents ) and smoking ( prevalence of 25.4 % among respondents ) did n't yield any significant difference in subjects with frequent symptoms . Importantly , we also found that only 52.8 % of subjects with frequent chest pain and 29.3 % of respondents with frequent heartburn had seen a physician for these symptoms Limited data exist to determine the prevalence and clinical spectrum of gastroesophageal reflux disease ( GERD ) in the Russian population , which might be different from those in Western countries . This study was performed in Moscow on r and omized 1065 adults aged ≥ 15 years . A vali date d reflux question naire comprising 72 questions and an additional 29 sub- questions were used . The questions assessed ( heartburn and regurgitation ) and related ( dyspepsia , dysphagia , odynophagia and chest pain ) symptoms , the triggering factors of these symptoms , family history and data on demographic and socioeconomic features . GERD was defined as heartburn and /or regurgitation once a week or common . Of the 1065 participants , 42.1 % were male and 57.9 % were female . The prevalences of frequent and occasional symptoms were 17.6 and 22.1 % for heartburn and 17.5 and 21.8 % for regurgitation , respectively , over the last 12 months . The prevalence of GERD was found to be 23.6 % . The rate of GERD was significantly higher in females than in males ( 15.4 vs. 29.5 % , P < 0.001 ) and significantly increased as the age of the participants increased ( P = 0.011 ) . GERD was present in 20.4 % of smokers , 24.2 % of coffee drinkers , 21.5 % of alcohol consumers and 45.9 % of stressed participants . Although the rate of alcohol consumers was lower in those with GERD compared with those without GERD , the rate of coffee drinkers and stressed participants was higher among those with GERD . The rate of additional symptoms was higher even in participants complaining of regurgitation/heartburn rarely , compared with those without complaints . Using the same question naire , which makes it possible to compare the present results with those from different countries , we found the prevalence of GERD in Moscow to be 23.6 % , one of highest in the Western population s. The rates of heartburn and regurgitation were found to be similar , which constitutes a different result than has been found in similar studies . Additional symptoms should be assessed , in all GERD patients even in the presence of rare complaints of regurgitation/heartburn The prevalence of gastroesophageal reflux disease ( GERD ) in China is lower than that in the Western countries , but appears to be increasing . The aim of this pilot study was to evaluate the prevalence of GERD in Shanghai , China , and to explore which population characteristics where associated with GERD . A sample of 1200 adult inhabitants of Shanghai , selected using r and omized , stratified , multi-stage sampling , completed M and arin translations of the Reflux Disease Question naire and GERD Impact Scale . Potential risk factors for GERD were examined by nested case-control analysis , using Cochran-Armitage trend testing and logistic regression analysis . The response rate was 86.2 % ; 919 responses were suitable for analysis . The prevalence of GERD , defined as heartburn and /or regurgitation of any frequency during the previous week , was 6.2 % in Shanghai . Obesity and urban dwelling were associated with GERD ( odds ratio 3.4 , 95 % confidence interval 1.3 - 9.3 ; and odds ratio 3.6 , 95 % confidence interval 1.2 - 10.4 , respectively ) . The prevalence of GERD in Shanghai agreed with previous Chinese studies . GERD in Shanghai was associated with obesity and residency in an urban environment |
10,311 | 32,420,142 | Conclusions Higher PD-L1 expression is more closely associated with poor prognosis and more advanced clinicopathological features in RCC patients than PD-L2 , especially in women and Caucasian patients .
PD-L2 was a weak negative predictor of poor CSS of RCC and was not a prompt for the metastasis of RCC | Background The research of the prognostic and clinicopathologic values of programmed cell death lig and 1/2 ( PD-L1/2 ) in renal cell carcinoma ( RCC ) patients has been mired by a dearth of studies and considerable controversy .
We thus conducted a systematic review and meta- analysis to report the prevalence and prognostic and clinicopathological value of programmed cell death lig and 1 ( PD-L1 ) and programmed cell death-legend 2 ( PD-L2 ) in RCC patients . | BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , Background Kidney and renal pelvis cancers account for 4 % of all new cancer cases in the United States , among which 85 % are renal cell carcinomas ( RCC ) . While cigarette smoking is an established risk factor for RCC , little is known about the contribution of environmental tobacco smoke ( ETS ) to RCC incidence . This study assesses the role of smoking and ETS on RCC incidence using a population -based case-control design in Florida and Georgia . Methods Incident cases ( n = 335 ) were identified from hospital records and the Florida cancer registry , and population controls ( n = 337 ) frequency-matched by age ( + /- 5 years ) , gender , and race were identified through r and om-digit dialing . In-person interviews assessed smoking history and lifetime exposure to ETS at home , work , and public spaces . Home ETS was measured in both years and hours of exposure . Odds ratios and 95 % confidence intervals were calculated using logistic regression , controlled for age , gender , race , and BMI . Results Cases were more likely to have smoked 20 or more pack-years , compared with never-smokers ( OR : 1.35 , 95 % CI : 0.93 – 1.95 ) . A protective effect was found for smoking cessation , beginning with 11–20 years of cessation ( OR : 0.39 , 95 % CI : 0.18–0.85 ) and ending with 51 or more years of cessation ( OR : 0.11 , 95 % CI : 0.03–0.39 ) in comparison with those having quit for 1–10 years . Among never-smokers , cases were more likely to report home ETS exposure of greater than 20 years , compared with those never exposed to home ETS ( OR : 2.18 ; 95 % CI : 1.14–4.18 ) . Home ETS associations were comparable when measured in lifetime hours of exposure , with cases more likely to report 30,000 or more hours of home ETS exposure ( OR : 2.37 ; 95 % CI : 1.20–4.69 ) . Highest quartiles of combined home/work ETS exposure among never-smokers , especially with public ETS exposure , increased RCC risk by 2 to 4 times . Conclusion These findings confirm known associations between smoking and RCC and establish a potential etiologic role for ETS , particularly in the home . Differences in methods of retrospective measurement of lifetime smoking and ETS exposure may contribute to discrepancies in measures of associations across studies , and should be addressed in future research Purpose Nivolumab , a programmed death-1 inhibitor , prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous ( CheckMate 017 ; Clinical Trials.gov identifier : NCT01642004 ) or nonsquamous ( CheckMate 057 ; Clinical Trials.gov identifier : NCT01673867 ) non-small-cell lung cancer ( NSCLC ) . We report up date d results , including a pooled analysis of the two studies . Methods Patients with stage IIIB/IV squamous ( N = 272 ) or nonsquamous ( N = 582 ) NSCLC and disease progression during or after prior platinum-based chemotherapy were r and omly assigned 1:1 to nivolumab ( 3 mg/kg every 2 weeks ) or docetaxel ( 75 mg/m2 every 3 weeks ) . Minimum follow-up for survival was 24.2 months . Results Two-year overall survival rates with nivolumab versus docetaxel were 23 % ( 95 % CI , 16 % to 30 % ) versus 8 % ( 95 % CI , 4 % to 13 % ) in squamous NSCLC and 29 % ( 95 % CI , 24 % to 34 % ) versus 16 % ( 95 % CI , 12 % to 20 % ) in nonsquamous NSCLC ; relative reductions in the risk of death with nivolumab versus docetaxel remained similar to those reported in the primary analyses . Durable responses were observed with nivolumab ; 10 ( 37 % ) of 27 confirmed responders with squamous NSCLC and 19 ( 34 % ) of 56 with nonsquamous NSCLC had ongoing responses after 2 years ' minimum follow-up . No patient in either docetaxel group had an ongoing response . In the pooled analysis , the relative reduction in the risk of death with nivolumab versus docetaxel was 28 % ( hazard ratio , 0.72 ; 95 % CI , 0.62 to 0.84 ) , and rates of treatment-related adverse events were lower with nivolumab than with docetaxel ( any grade , 68 % v 88 % ; grade 3 to 4 , 10 % v 55 % ) . Conclusion Nivolumab provides long-term clinical benefit and a favorable tolerability profile compared with docetaxel in previously treated patients with advanced NSCLC |
10,312 | 32,312,252 | In subgroup analyses , elevated pretreatment platelet counts were also associated with poorer OS and DFS/PFS/TTP in most subgroups .
This meta- analysis revealed that elevated pretreatment platelet counts were an independent predictor of OS and DFS/PFS/TTP in lung cancer patients . | The prognostic value of elevated pretreatment platelet counts remains controversial in lung cancer patients .
We performed the present meta- analysis to determine its precise role in these patients . | BACKGROUND The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear . METHODS We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome . Human sample s and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis . The effects of platelets on tumor growth and angiogenesis were ascertained . RESULTS Thrombocytosis was significantly associated with advanced disease and shortened survival . Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not . In mouse models , increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis . Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients . Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice . Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer . In addition , neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer . The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis . CONCLUSIONS These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis , which fuels tumor growth . We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential . ( Funded by the National Cancer Institute and others . ) PURPOSE This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group . PATIENTS AND METHODS We included in the analysis all eligible patients ( N = 1,052 ) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party ( ELCWP ) during one decade . The patients were treated by chemotherapy regimens based on platinum derivatives . We prospect ively collected 23 variables and analyzed them by univariate and multivariate methods . RESULTS The global estimated median survival time was 29 weeks , with a 95 % confidence interval of 27 to 30 weeks . After univariate analysis , we applied two multivariate statistical techniques . In a Cox regression model , the selected explanatory variables were disease extent , Karnofsky performance status , WBC and neutrophil counts , metastatic involvement of skin , serum calcium level , age , and sex . These results were confirmed by application of recursive partitioning and amalgamation algorithms ( RECPAM ) , which led to classification of the patients into four homogeneous subgroups . CONCLUSION We confirmed by our analysis the role of well-known independent prognostic factors for survival , but also identified the effect of the neutrophil count , rarely studied , with the use of two methods : a classical Cox regression model and a RECPAM analysis . The classification of patients into the four subgroups we obtained needs to be vali date d in other series We have evaluated the prognostic value of 22 pretreatment attributes in 436 small cell lung cancer ( SCLC ) patients included in a prospect i ve multicenter study with a minimum 5-year follow-up . Pretreatment clinical and laboratory parameters were registered . Possible prognostic factors were evaluated by univariate analysis ( log rank test ) and by the Cox multivariate regression model . In the univariate analysis of all patients , only age , nodal metastasis , and skin metastasis were not associated with survival . The multivariate Cox model identified gender , extent of disease , performance status ( PS ) , weight loss , platelet count , LDH , and NSE as independent prognostic factors . In subset multivariate analyses according to extent of disease , we found haemoglobin level , PS , NSE , and total WBC as significant prognostic indicators for survival in limited-stage disease ( LD-SCLC ) , while PS , weight loss , LDH , number of metastases , liver metastases , and brain metastases were identified as independent prognostic factors in extensive-stage disease ( ED-SCLC ) . There was a significant correlation between serum LDH and NSE levels . In conclusion , gender , extent of disease , PS , weight loss , haemoglobin , WBC count , platelet count , LDH , and NSE were all found to be independent prognostic factors for SCLC survival . However , the prognostic value of these factors depends highly on whether all or subsets of SCLC patients are studied There is a sub clinical activation of coagulation and fibrinolysis system in lung cancer . Alterations in hemostatic system are seen frequently in lung cancer correlated with the prognosis of disease . In this prospect i ve study , our purpose was to investigate the prognostic significance of hemostatic markers in patients with lung cancer . The study comprised 58 patients ( 22 squamous cell carcinoma , 16 adenocarcinoma , 20 small cell carcinoma ) . There were 55 men ( 95 % ) and 3 women ( 5 % ) with a mean age of 61 years range ( 36 - 74 ) . Plasma level of platelets ( PLT ) , prothrombin time ( PT ) , active partial thromboplastin time ( aPTT ) , antithrombin III ( AT III ) , fibrinogen ( F ) and D-dimer level were measured before the initiation of any therapy . Patients were followed up for 17 ( 12 - 20 ) months . The median survival was determined as 6.4 months . Three histopathologic groups ; squamous cell carcinoma , adenocarcinoma and small cell carcinoma were compared for the hemostatic parameters . There were no statistically significant differences among the histopathologic types for any of the parameters ( P > 0.05 ) . Patients were divided into two groups as patients without distant metastasis ( stages I , II , III ) and with distant metastasis ( stage IV ) . The group with distant metastasis had higher level of D-dimer than the other group ( P < 0.05 ) . However , there were no statistically significant differences for D-dimer level between stages IIIB and IV ( P > 0.05 ) . Patients having high D-dimer and low AT III level had poor survival in our study . Thus , high level of D-dimer and low AT III level were determined as correlated with short survival ( P < 0.05 ) . These results suggest that elevated plasma level of D-dimer and low AT III level might be a sign of poor prognosis in patients with lung cancer INTRODUCTION FRAME was a prospect i ve observational study that captured real-world data on patients with advanced or metastatic non-small cell lung cancer ( NSCLC ) receiving platinum-based chemotherapies as first-line treatment ( FLT ) across Europe . As previously reported , most patients observed in the study had initiated FLT with either pemetrexed , gemcitabine , vinorelbine or taxanes in combination with a platinum . Baseline patient and disease characteristics including age , performance status , and histology varied ( all p<0.01 ) across cohorts . METHODS Consenting adult patients initiating FLT for advanced or metastatic NSCLC with platinum-based chemotherapy , with or without a targeted agent , entered the study between April 2009 and February 2011 . The choice of FLT was left to physicians ' discretion per routine clinical practice . The primary objective was to evaluate overall survival ( OS ) across platinum-based doublet chemotherapy cohorts and key secondary objectives included the evaluation of OS in patients with different histological subtypes of NSCLC . Survival outcomes were assessed using Kaplan-Meier analysis , and unadjusted estimates are presented . RESULTS Median OS in months was 10.3 across cohorts ( n=1524 ) , 10.7 for pemetrexed ( n=569 ) , 10.0 for gemcitabine ( n=360 ) , 9.1 for taxanes ( n=295 ) , and 10.7 for vinorelbine ( n=300 ) . For patients with non-squamous NSCLC who received cisplatin ( n=616 , 40 % of total ) , median OS in months was 10.6 across the cohorts , 11.6 for pemetrexed , 8.4 for gemcitabine , 9.6 for taxanes , and 9.9 for vinorelbine . CONCLUSIONS FRAME describes real-world treatment patterns and survival for patients initiating FLT for advanced or metastatic NSCLC between 2009 and 2011 across Europe Background : The aim of the present study was to investigate any prognostic value of pre-treatment anemia , leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC . Methods : A r and omized , multicenter phase II study comparing the IGF-1R modulator AXL with st and ard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011 - 2013 . Clinical and laboratory data were collected , including serum values for hemoglobin ( Hgb ) , white blood cells ( WBC ) and platelets ( Plt ) at baseline . These hematological parameters were studied in relation to overall survival using Kaplan – Meier product-limit estimates and multivariate Cox proportional hazards regression models . Results : The median overall survival for all patients was 8.9 months . Patients with leukocytosis ( WBC > 9 x 109/L ) had a significantly shorter median overall survival ( 4.2 months ) as compared with those with a WBC ≤ 9 x 109/L at baseline ( 12.3 months ) with a corresponding of HR 2.10 ( 95 % CI : 1.29 - 3.43 ) . Patients with anemia ( Hgb < 110 g/L ) had a non-significant ( p = 0.097 ) shorter median overall survival ( 6.1 months ) as compared with their counterparts with Hgb ≥ 110 g/L at baseline ( 9.4 months ) . As for thrombocytosis ( Plt > 350 x 109/L ) , there was no statistically significant impact on overall survival . Leukocytosis retained its prognostic significance in a multivariate model where other clinical factors such as age , sex and WHO performance status were taken into consideration ( HR : 1.83 , 95 % CI : 1.06 - 3.13 , p = 0.029 ) . Conclusion : Pre-treatment leukocytosis is a strong and independent prognostic marker for shorter overall survival in previously treated stage IIIB or IV NSCLC patients receiving docetaxel or AXL1717 . Combined use of pre-treatment leukocytosis assessment s together with established prognostic factors such as performance status could be of help when making treatment decisions in this clinical setting AIMS An elevated plasma D-dimer level indicates the activation of coagulation and fibrinolysis . In the present study , we investigated the association of pre-treatment haemostatic parameters ( D-dimer , fibrinogen and prothrombin fragment 1 + 2 ) with clinicopathological parameters and outcome in patients with lung cancer . MATERIAL S AND METHODS Plasma levels of D-dimer and other parameters were measured in 78 evaluable patients with lung cancer ( 60 non-small cell lung cancers , 18 small cell lung cancers ) . At diagnosis , 35 patients ( 44.9 % ) were locally advanced stage ( IIIA/B ) and 43 patients ( 55.1 % ) had metastatic disease ( IV ) . Multivariate statistical analysis was carried out using Cox 's proportional hazards model . The receiver operating characteristic curve was used to determine the cut-off values for D-dimer , fibrinogen and prothrombin fragment 1 + 2 . RESULTS The median survival for all patients was 264 days ( 95 % confidence interval 200 - 328 days ) . A significant association between the plasma levels of D-dimer and the response to chemotherapy was observed ( P=0.03 ) . With the univariate analysis , tumour stage , pre-treatment plasma levels of D-dimer , fibrinogen , platelet count , lactate dehydrogenase concentration and Karnofsky performance status were predictive for survival . With the multivariate analysis ( P < or = 0.1 ) , the plasma level of D-dimer ( P<0.001 ) , tumour stage ( P=0.01 ) and Karnofsky performance status ( P=0.02 ) were identified as independent predictive factors . The median survival times were 405 days ( 95 % confidence interval 165 - 644 days ) and 207 days ( 95 % confidence interval 146 - 267 days , P<0.001 ) , respectively , for patients with a low D-dimer level ( < or = 0.65 microg/ml ) and a high D-dimer level ( > 0.65 microg/ml ) . CONCLUSIONS Elevated plasma levels of D-dimer in patients with lung cancer are associated with decreased survival and a poor response to treatment . Pre-treatment for the D-dimer level may be useful in the prediction of survival and the response to treatment |
10,313 | 21,811,185 | CONCLUSIONS The most consistent and effective attenuation of EIB was observed with high-intensity interval and variable intensity preexercise warm-ups .
These findings indicate that an appropriate warm-up strategy that includes at least some high-intensity exercise may be a short-term nonpharmacological strategy to reducing EIB | PURPOSE Exercise-induced bronchoconstriction ( EIB ) occurs when vigorous exercise induces bronchoconstriction .
Preexercise warm-up routines are frequently used to elicit a refractory period and thus reduce or prevent EIB .
This study aim ed to conduct a systematic review to evaluate the effectiveness of preexercise routines to attenuate EIB . | OBJECTIVES : To study factors affecting the occurrence of exercise induced bronchospasm ( EIB ) in elite runners . METHODS : Fifty eight elite runners , 79 % of them belonging to Finnish national teams , volunteered . The athletes answered a question naire on respiratory symptoms . Skin prick tests were used to investigate atopy , and spirometry to examine lung function at rest and after an exercise challenge test ( ECT ) at subzero temperature in the winter and after a similar ECT in the summer at the end of the birch pollen season . RESULTS : Definitive EIB ( a post-exercise reduction of 10 % or more in forced expiratory volume in one second ( FEV1 ) was observed in five ( 9 % ) of the 58 runners . A subgroup consisting of 19 non-atopic symptom-free runners with no family history of asthma was used to establish a normal range for post-exercise reduction in FEV1 . When this group 's mean exercise induced change in FEV1 minus 2 SDs ( a reduction of 6.5 % or more in FEV1 ) was taken as the lower limit of the reference range , 15 ( 26 % ) of the runners had probable EIB in either the winter or the pollen season . The occurrence of probable EIB depended on atopy ( odds ratio increased with number of positive skin prick test reactions , p < 0.05 ) . Nine ( 22 % ) of the 41 runners , challenged in both the winter and the pollen season , had probable EIB only in the winter , and three ( 7 % ) had it only in the pollen season . Only one runner ( 2 % ) had EIB in both tests . CONCLUSIONS : Mild EIB is common in Finnish elite runners and is strongly associated with atopy . Seasonal variability affects the occurrence of EIB , and thus exercise testing should be performed in both cold winter air and the pollen season to detect EIB in elite runners To determine the effect of two forms of warm-up on postexercise bronchoconstriction in athletes with exercise-induced asthma , 12 moderately trained persons with asthma ( age = 26.5 + /- 2.2 yr ; height = 169.2 + /- 2.6 cm ; weight = 64.3 + /- 2.6 kg ; VO2max = 52.7 + /- 1.3 ml.kg-1.min-1 ) were tested under three experimental conditions ; continuous warm-up ( CW ) , interval warm-up ( IW ) , and control ( C ) . CW consisted of 15 min of treadmill running at a velocity corresponding to 60 % VO2max followed by an exercise challenge test ( ET = 6 min at 90 % VO2max ) . IW involved 8 x 30-s runs ( 1.5 min rest between bouts of exercise ) , at an intensity equivalent to 100 % VO2max , followed by an ET . C consisted of only the ET . FEV1 , FVC , and MMEFR were measured prior to the experimental conditions , repeated before the ET , and every 2 min during a 25-min passive recovery period , using a Breon spirometer . Postexercise changes in pulmonary function were recorded as the largest decrese in FEV1 , FVC , and MMEFR during the recovery period , and expressed as a percentage of baseline values . Significant differences were detected in % FEV1 ( 34 . 6,16.7,29.7 : P = 0.009 ) , % FVC ( 30.0,10.7,21.0 : P = 0.03 ) , and % MMEFR ( 50.0,30.2,43.4 : P = 0.05 ) , in comparing C , CW , and IW , respectively . Scheffe 's test detected significance ( P < 0.05 ) between C and CW for all three dependent variables ; no statistical significance between C and IW or IW and CW occurred . These data indicate that a continuous warm-up of 15 min at 60 % VO2max can significantly decrease postexercise bronchoconstriction in moderately trained athletes The effect of a prolonged warm-up period of exercise on subjects with exercise-induced asthma ( EIA ) has been studied . Seven asthmatic subjects with known EIA were exercised according to two different protocol s on two separate days , which were r and omized . On Day A , subjects performed a st and ard 6-min treadmill run ( S1A ) , which increased heart rate to 98 % predicted maximum , followed 45 min later by an identical run ( S2A ) . Refractoriness was demonstrated on the second exercise test , with a mean maximal fall in FEV1 of 29 + /- 3.1 % and a PEFR of 32 + /- 2.8 % after S2A , compared with a mean maximal fall in FEV1 of 46 + /- 2.6 % and a PEFR of 51 + /- 4.0 % after S1A . On Day B , subjects performed a 30-min treadmill run at a lower gradient ( W1B ) , followed 21 min later by another st and ard 6-min treadmill test ( S2B ) . W1B was followed by significantly less EIA ( mean maximal fall in FEV1 of 17 + /- 5.4 % and a PEFR of 21 + /- 6.3 % ) than followed S1A . Nevertheless , when subjects subsequently performed a st and ard 6-min run ( S2B ) , significant refractoriness to bronchoconstriction , comparable to that observed after S2A , developed , with a mean maximal fall in FEV1 of 26 + /- 3.6 % and a PEFR of 27 + /- 2.3 % ( p less than 0.05 ) . We conclude that a warm-up period of exercise can induce refractoriness to EIA without itself inducing marked bronchoconstriction There are two apparently conflicting theories on the pathogenesis of exercise-induced asthma . One view is that exercise-induced asthma is directly related to respiratory heat exchange and that mast cells are not involved . The other theory explains exercise-induced asthma on the basis of a temperature-independent release of mast-cell mediators . A theory is put forward here that airway cooling in asthmatic subjects during exercise leads directly to mast-cell degranulation and that this explains the association between exercise , respiratory heat exchange , and mediator release |
10,314 | 27,590,620 | The effect of antimicrobial coating was similar between different suture , wound , and procedure types .
Triclosan-coated sutures may reduce SSI risk . | To investigate the effectiveness of antimicrobial-coated sutures compared with non-coated sutures in reducing surgical site infection ( SSI ) and develop recommendations for World Health Organization ( WHO ) SSI prevention guidelines . | BACKGROUND Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery , and triclosan-coated sutures were developed to reduce their occurrence . The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure , compared with non-coated PDS II sutures , in the prevention of surgical site infections . METHODS This multicentre , r and omised controlled group-sequential superiority trial was done in 24 German hospitals . Adult patients ( aged ≥18 years ) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion . Exclusion criteria were impaired mental state , language problems , and participation in another intervention trial that interfered with the intervention or outcome of this trial . A central web-based r and omisation tool was used to r and omly assign eligible participants by permuted block r and omisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures ( PDS Plus ) or uncoated sutures ( PDS II ) for abdominal fascia closure . The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation . Patients , surgeons , and the outcome assessors were masked to group assignment . Interim and final analyses were by modified intention to treat . This trial is registered with the German Clinical Trials Register , number DRKS00000390 . FINDINGS Between April 7 , 2010 , and Oct 19 , 2012 , 1224 patients were r and omly assigned to intervention groups ( 607 to PDS Plus , and 617 to PDS II ) , of whom 1185 ( 587 PDS Plus and 598 PDS II ) were analysed by intention to treat . The study groups were well balanced in terms of patient and procedure characteristics . The occurrence of surgical site infections did not differ between the PDS Plus group ( 87 [ 14·8 % ] of 587 ) and the PDS II group ( 96 [ 16·1 % ] of 598 ; OR 0·91 , 95 % CI 0·66 - 1·25 ; p=0·64 ) . Serious adverse events also did not differ between the groups-146 of 583 ( 25·0 % ) patients treated with PDS Plus had at least one serious adverse event , compared with 138 of 602 ( 22·9 % ) patients treated with PDS II ; p=0·39 ) . INTERPRETATION Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy . Innovative , multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections . FUNDING Johnson & Johnson Medical Limited OBJECTIVES The incidence of surgical site infection ( SSI ) after open vein harvesting in coronary artery bypass grafting ( CABG ) patients ranges in different studies between 2 and 20 % . Triclosan is an antibacterial substance that reduces the growth of bacteria by inhibiting fatty acid synthesis . We hypothesized that wound closure with triclosan-coated sutures would reduce SSI after open vein harvesting . METHODS An investigator-initiated prospect i ve r and omized double-blind single-centre study was performed with 374 patients , r and omized to subcutaneous and intracutaneous leg-wound closure with either triclosan-coated sutures ( Vicryl Plus ® and Monocryl Plus ® , Ethicon , Somerville , NJ , USA ) ( n = 184 ) or identical sutures without triclosan ( n = 190 ) from the same manufacturer . All patients were followed up after 30 days ( clinical visit ) and 60 days ( telephone interview ) . Primary endpoint was SSI within 60 days after surgery according to the definition of Center for Disease Control . Predefined secondary endpoints included culture-proven and antibiotic-treated SSI . RESULTS The primary endpoint occurred in 23 patients ( 12.5 % ) with triclosan-coated sutures and in 38 patients ( 20.0 % ) in the group without triclosan ( P = 0.0497 , risk ratio 0.63 , ( 95 % confidence interval 0.39–1.00 ) . Corresponding figures for culture-proven infections were 7.6 vs 12.1 % , ( P = 0.15 ) , and for antibiotic-treated infections , 10.9 vs 18.4 % , ( P = 0.039 ) . Staphylococcus aureus and coagulase-negative staphylococci were the most common pathogens in both groups . Insulin-treated diabetes and vein-harvesting time were associated with SSI after vein harvesting . CONCLUSIONS Leg-wound closure with triclosan-coated sutures in CABG patients reduces SSIs after open vein harvesting . ( Clinical Trials.gov number NCT01212315 ) OBJECT Implantation of cerebrospinal fluid ( CSF ) shunting devices is associated with a 5 - 15 % risk of infection as cited in contemporary pediatric neurosurgical literature . Shunt infections typically require complete removal of the device and prolonged antibiotic treatment followed by shunt replacement . Moreover , shunt infections are commonly associated with prolonged hospital stays , potential comorbidity , and the increased risk of neurological compromise due to ventriculitis or surgical complications . The authors prospect ively evaluated the incidence of CSF shunt infection following shunt procedures performed using either antimicrobial suture ( AMS ) or conventional suture . METHODS In a single-center , prospect i ve , double-blinded , r and omized controlled trial , the authors enrolled 61 patients , among whom 84 CSF shunt procedures were performed over 21 months . R and omization to the study ( AMS ) or control ( placebo ) group was stratified to minimize the effect of known shunt infection risk factors on the findings . Antibacterial shunt components were not used . The primary outcome measure was the incidence of shunt infection within 6 months of surgery . RESULTS The shunt infection rate in the study group was 2 ( 4.3 % ) of 46 procedures and 8 ( 21 % ) of 38 procedures in the control group ( p = 0.038 ) . There were no statistically significant differences in shunt infection risk factors between the groups ( procedure type and time , age < 6 months , weight < 4 kg , recent history of shunt infection ) . No suture-related adverse events were reported in either group . CONCLUSIONS These results support the suggestion that the use of AMS for CSF shunt surgery wound closure is safe , effective , and may be associated with a reduced risk of postoperative shunt infection . A larger r and omized controlled trial is needed to confirm this association BACKGROUND Surgical site infection ( SSI ) is the fourth commonest healthcare-associated infection and complicates at least 5 % of open operations . In a r and omized clinical trial , antimicrobial-coated sutures were compared with their conventional counterparts , polyglactin and poliglecaprone , for skin closure after breast cancer surgery to assess their role in reducing the rate of SSI . METHODS Between November 2008 and February 2011 , 150 female patients presenting with breast cancer to a single center were r and omized to skin closure with antimicrobial-coated or plain sutures . Postoperatively , SSI was defined using the U.S. Centers for Disease Control and Prevention ( CDC ) definitions and scored using the ASEPSIS or Southampton systems by trained , blinded observers with close post-discharge surveillance and patient diaries . Surgeons and patients were blinded to the type of suture used . RESULTS Using CDC criteria , the overall rate of SSI was 18.9 % at six weeks . Six patients ( 4.7 % ) needed intervention or readmission for SSI . Skin closure with antimicrobial sutures showed a non-statistically significant reduction in the SSI rate , to 15.2 % , compared with conventional sutures ( 22.9 % ) . A uniform tendency for fewer SSIs in the antimicrobial-coated suture group was found using ASEPSIS and Southampton scores , but again , the difference was not statistically significant . CONCLUSION The previously reported high rate of SSI related to breast surgery was confirmed . Using statistical modeling and earlier reports , the study was powered to show a difference using ASEPSIS scores , but the modification used in this trial failed to find a difference . Finding a statistically significant difference would have needed two to three times the number of patients recruited . Further evaluation of antimicrobial-coated sutures is merited , particularly if used as part of a care bundle to reduce SSI after breast cancer surgery 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 The primary objective of this multicenter post-market study was to compare the cosmetic outcome of triclosan-coated VICRYL Plus sutures with Chinese silk sutures for skin closure of modified radical mastectomy . A secondary objective was to assess the incidence of surgical site infection ( SSI ) . METHODS Patients undergoing modified radical mastectomy were r and omly assigned to coated VICRYL Plus antibacterial ( Polyglactin 910 ) suture or Chinese silk suture . Cosmetic outcomes were evaluated postoperatively at days 12 ( ± 2 ) and 30 ( ± 5 ) , and the evidence of SSI was assessed at days 3 , 5 , 7 , 12 ( ± 2 ) , 30 ( ± 5 ) , and 90 ( ± 7 ) . Cosmetic outcomes were independently assessed via visual analogue scale ( VAS ) score evaluations of blinded incision photographs ( primary endpoint ) and surgeon-assessed modified Holl and er Scale ( mHCS ) scores ( secondary endpoint ) . SSI assessment s used both CDC criteria and ASEPSIS scores . RESULTS Six Chinese hospitals r and omized 101 women undergoing modified radical mastectomy to closure with coated VICRYL Plus suture ( n = 51 ) or Chinese silk suture ( n = 50 ) . Mean VAS cosmetic outcome scores for antibacterial suture ( 67.2 ) were better than for Chinese silk ( 45.4 ) at day 30 ( P < 0.0001 ) ) . Mean mHCS cosmetic outcome total scores , were also higher for antibacterial suture ( 5.7 ) than for Chinese silk ( 5.0 ) at day 30 ( P = 0.002 ) . CONCLUSIONS Patients using coated VICRYL Plus suture had significantly better cosmetic outcomes than those with Chinese silk sutures . Patients using coated VICRYL Plus suture had a lower SSI incidence compared to the Chinese silk sutures , although the difference did not reach statistical significance OBJECTIVE To evaluate the efficacy and safety of new antibacterial suture ( Vicryl Plus ) compared with a traditional braided suture ( Vicryl ) in a clinical study . The primary goal was to study effectiveness on reduced surgical site infection in an appendectomy operation . The authors ' secondary goal was to analyze the safety and physical properties of Vicryl plus . MATERIAL AND METHOD This was a prospect i ve , r and omized , controlled , double blind , comparative , single-center study . After appendectomy was done , the patients were r and omized in two groups : Vicryl Plus and Vicryl to selected suture for suturing the abdominal sheath . The surgical site infection was evaluated for 30 days , 6 months , and 1 year . The surgeons and attending doctor were blind to the type of suture . This is the primary report of the first 100 patients . RESULTS There was no difference in demographic and preoperative clinical in both groups . Although there was no statistical difference in the surgical site infection of Vicryl and Vicryl Plus ( 8 and 10 % , p = 0.05 ) , one case of deep surgical site infection was detected in the Vicryl group . No complications and no difference in related suture material s were detected . CONCLUSION Coated polyglactin 910 with tricosan ( Vicryl Plus ) is safe and satisfactory in surgical practice . Surgical site infection of appendectomy seemed too to be comparable between coated polyglactin 910 with tricosan ( Vicryl Plus ) and traditional polyglactin 910 ( Vicryl ) group BACKGROUND Surgical wound infection is a common complication , which increases the hospital stay and costs after surgery for head and neck cancer . In this study , we evaluated the effect of Triclosan-coated sutures on surgical wounds and analyzed the risk factors for wound infections in head and neck cancer surgery . PATIENTS AND METHODS From January 2007 to December 2009 , 253 consecutive patients underwent wide excision of a head or neck cancer and reconstructive procedures . All patient data were collected prospect ively . Of these , 241 patients were included in this study , divided into two groups . The Triclosan group contained 112 patients , whose surgical wounds were closed with Triclosan-coated sutures ( Vicryl Plus ) . The control group included the remaining 129 patients , whose surgical wounds were closed with conventional Vicryl sutures . We conducted a retrospective , multivariate analysis to determine independent risk factors for the cervical wound infection . RESULTS The cervical wound infection rate was 14.9 % ( 17/112 ) in the Triclosan group and 14.7 % ( 19/129 ) in the control group , and these rates were not significantly different . Tumour stage and delayed intra-oral flap healing were independent risk factors for cervical wound infection . CONCLUSIONS In this preliminary study , Triclosan-coated Vicryl sutures did not reduce the infection rate of cervical wounds after head or neck cancer surgery . The effectiveness of this suture material in head and neck cancer surgery should be considered with caution OBJECTIVE Postoperative surgical site infections ( SSI ) still greatly affect mortality and morbidity in cardiovascular surgery . SSI may be related to the suture material . In this prospect i ve , r and omized , controlled , and double-blinded study , the effect of antibacterial suture material on SSI in cardiac surgical patients was investigated . METHODS We r and omly allocated 510 patients into 2 groups . Antibacterial suture material s were used for wound closure in 170 patients ( triclosan-coated suture group ) , and routine suture material s were used in 340 patients ( noncoated suture group ) . All patients were evaluated for SSI on days 10 , 20 , and 30 following cardiac surgery . RESULTS Preoperative risk factors and laboratory findings were comparable for the 2 groups . Sternal infection occurred in 4 ( 2.4 % ) of the patients in the triclosan-coated suture group and in 3.5 % of the noncoated suture group ( P > .05 ) . Leg wound infection occurred in 5 ( 3.5 % ) of the patients in the triclosan-coated suture group and in 3.8 % of the noncoated suture group ( P > .05 ) . Only diabetes mellitus was an independent predictor of SSI . CONCLUSION Both noncoated and triclosan-coated suture material s are safe . Larger studies may be needed to show the benefit and cost-effectiveness , if any , of triclosan-coated material s over noncoated material OBJECTIVES Leg wound infection is a common complication after coronary artery bypass grafting ( CABG ) . Suture contamination has been suggested as a mechanism of surgical site infections . Vicryl Plus ( ® ) is a polyglacitin suture coated with the antiseptic chemical substance Triclosan , which has been shown to inhibit the growth of Staphylococcus aureus in vitro . The first aim of the present study was to compare Vicryl Plus with conventional Vicryl ( ® ) sutures with regard to leg wound infections following CABG . The second aim was to examine patient- and operative characteristics , which are assumed to predict leg wound infections . METHODS After statistical calculations a priori , 328 CABG patients were prospect ively r and omized to leg wound closure with Vicryl Plus ( 164 patients ) or conventional Vicryl sutures ( 164 patients ) . Incidences of leg wound infection and predictors of infection related to patient- and operative characteristics were examined . RESULTS The incidence of leg wound infections was 10.4 % ( 17/163 ) in the Vicryl group , and 10.0 % ( 16/160 ) in the Vicryl Plus group ( P = 1.00 ) . Patients with leg wound infections had increased body mass index and prolonged extracorporeal circulation and aortic clamping time compared with patients without infections . CONCLUSIONS In the present study , we report for the first time that Vicryl Plus did not reduce the incidence of leg wound infections in patients undergoing CABG . Obesity and prolonged time of extracorporeal circulation were both associated with the increased risk of infections . Currently , the clinical role and indication for the use of Vicryl Plus have yet to be defined This study compared Triclosan coated polyglactin 910 ( Vicryl * Plus ) with polyglactin 910 ( Vicryl * ) on abdominal wall healing in colorectal surgery patients . 184 patients with colorectal cancer were included in the study . In 91 , the abdominal wall was closed with the Vicryl * Plus , and in 93 patients with Vicryl*. Demographic characteristics , biochemical inflammatory parameters , wound appearance , length of hospital stay , postoperative wound complications and post-incisional hernia were recorded . In the Vicryl * Plus group there was a shorter hospital stay ( 13.2 + /- 1.3 days ; 21.4 + /- 2.8 respectively ) . In the Vicryl * Plus group inflammatory parameters decreased to normal within the first week whereas in the Vicryl * group remained increased . In the Vicryl * Plus group four patients had a wound discharge , seven had inflammatory reactions to the skin sutures . One dehiscence was noticed . In the Vicryl * group 12 patients had an SSI , 14 patients had inflammatory reactions to the skin sutures and 7 patients had a wound dehiscence . Closure of the abdominal wall using Vicryl * Plus decreases postoperative wound complications , length of hospital stay and is associated with a more rapid return of inflammatory markers to normal Objective : The objective of this article is to systematic ally analyse the r and omized , controlled trials that compare the use of antibacterial sutures ( ABS ) for skin closure in controlling surgical site infections . Methods : R and omized , controlled trials on surgical patients comparing the use of ABS for skin closure in controlling the surgical site infections were analysed systematic ally using RevMan ® and combined outcomes were expressed as odds ratios ( OR ) and st and ardized mean differences ( SMD ) . Results : Seven r and omized , controlled trials evaluating 1631 patients were retrieved from electronic data bases . There were 760 patients in the ABS group and 871 patients in the simple suture group . There was moderate heterogeneity among trials ( Tau2 = 0.12 ; chi2 = 8.40 , df = 6 [ P < 0.01 ] ; I2 = 29 % ) . Therefore in the r and om-effects model , the use of ABS for skin closure in surgical patients was associated with a reduced risk of developing surgical site infections ( OR , 0.16 ; 95 % CI , 0.37 , 0.99 ; z = 2.02 ; P < 0.04 ) and postoperative complications ( OR , 0.56 ; 95 % CI , 0.32 , 0.98 z = 2.04 ; P = 0.04 ) . The duration s of operation and lengths of hospital stay were similar following the use of ABS and SS for skin closure in patients undergoing various surgical procedures . Conclusion : Use of ABS for skin closure in surgical patients is effective in reducing the risk of surgical site infection and postoperative complications . ABS is comparable with SS in terms of length of hospital stay and duration of operation BACKGROUND Poor wound healing and the development of infection in incisional wounds continue to be among the most common complications of open abdominal surgery . Various bacteria may contaminate not only the tissue in the operative wound , but also the actual suture material . To prevent the contamination of suture material in surgical wounds , triclosan-coated polyglactin 910 suture material s with antibacterial activity ( Vicryl plus ) was developed . The aim of this study was to ascertain if the use of Vicryl plus reduced the number of wound infections after midline laparotomy comparing to polydioxanon suture ( PDS II ) . METHODS We performed 2,088 operations in our department between October 2004 and September 2006 via midline incision . In the first time period ( TP1 ) , a PDS II loop suture was used . In the second time period ( TP2 ) , we used Vicryl plus . All variables were recorded prospect ively in a data base . The primary outcome was the number of wound infections . Risk factors for poor wound healing were collected prospect ively to compare the 2 groups . RESULTS Using a PDS loop suture for abdominal wall closure in TP1 , 10.8 % of patients with wound infections were detected . The number of patients with wound infections decreased in TP2 using Vicryl plus for abdominal wall closure to 4.9 % ( P < .001 ) despite no other changes in protocol s of patient care . Other risk factors for the development of site infections were comparable in the 2 groups . CONCLUSION The use of antibiotic-coated loop suture for abdominal wall closure can decrease the number wound infections after abdominal surgery BACKGROUND CONTEXT Surgical site infection ( SSI ) is a serious postoperative complication . The incidence of SSIs is lower in clean orthopedic surgery than in other fields , but it is higher after spinal surgery , reaching 4.15 % in high-risk patients . Several studies reported that triclosan-coated polyglactin 910 sutures ( Vicryl Plus ; Ethicon , Inc. , Somerville , NJ , USA ) significantly reduced the infection rate in the general surgical , neurosurgical , and thoracic surgical fields . However , there have been no studies on the effects of such coated sutures on the incidence of SSIs in orthopedics . PURPOSE To compare the incidence of wound infections after spinal surgery using triclosan-coated suture material s with that of noncoated ones . STUDY DESIGN / SETTING A retrospective , nonr and omized , and clinical study . PATIENT SAMPLE From May 2010 to April 2012 , 405 patients underwent a spinal surgical procedure in the Department of Orthopedic Surgery of two university hospitals . OUTCOME MEASURES The primary outcome was the number of wound infections and dehiscences . METHODS Two hundred five patients had a conventional wound closure with polyglactin 910 suture ( Vicryl ) between May 2010 and April 2011 ( Time Period 1 [ TP1 ] ) , and 200 patients underwent wound closure with triclosan-coated polyglactin 910 suture ( Vicryl Plus ) between May 2011 and April 2012 ( TP2 ) . Statistical comparisons of wound infections , dehiscence , and risk factors for poor wound healing or infection were performed . None of the authors has any conflict of interest associated with this study . RESULTS There were two cases of wound dehiscence in TP1 and one in TP2 ( p=.509 ) . Using noncoated sutures in TP1 , eight patients ( 3.90 % ) had wound infections , whereas one patient ( 0.50 % ) had wound infections in TP2 ( using triclosan-coated sutures ) ; the difference was significant ( p=.020 ) . CONCLUSIONS The use of triclosan-coated polyglactin 910 sutures instead of polyglactin 910 sutures may reduce the number of wound infections after spinal surgery BACKGROUND Coated polyglactin 910 suture with triclosan was developed recently in order to imbue the parent suture , coated polyglactin 910 , with antibacterial activity against the most common organisms that cause surgical site infections ( SSI ) . Because such alterations could alter the physical properties of the suture , this study sought to compare the intraoperative h and ling and wound healing characteristics of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture in pediatric patients undergoing various general surgical procedures . METHODS This was a prospect i ve , r and omized , controlled , open-label , comparative , single-center study . Pediatric patients ( age 1 - 18 years ) undergoing various surgical procedures were r and omized in a 2:1 ratio to treatment with either coated polyglactin 910 suture with triclosan or coated polyglactin 910 suture . The primary endpoint was the surgeon 's assessment of the overall intraoperative h and ling of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture without triclosan . The secondary endpoints included specific intraoperative suture h and ling measures and wound healing assessment s. The suture h and ling measures were ( 1 ) ease of passage through tissue ; ( 2 ) first-throw knot holding ; ( 3 ) knot tie-down smoothness ; ( 4 ) knot security ; ( 5 ) surgical h and ling ; ( 6 ) surgical h and ; ( 7 ) memory ; and ( 8) suture fraying . Assessment of wound healing included the following : Healing progress , infection , edema , erythema , skin temperature , seroma , suture sinus , and pain . Adverse events were recorded . RESULTS Scores for intraoperative h and ling were favorable and not significantly different for both sutures , although coated polyglactin 910 suture with triclosan received more " excellent " scores ( 71 % vs. 59 % ) . Wound healing characteristics were comparable for both sutures except for pain on postoperative day 1 . Significantly fewer patients treated with polyglactin 910 suture with triclosan reported pain on day 1 than patients who received the other suture ( 68 % vs. 89 % , p = 0.01 ) . The overall incidence of adverse events was 18 % ; none was devicerelated . CONCLUSIONS Coated polyglactin 910 suture with triclosan performed as well or better than traditional coated polyglactin 910 suture in pediatric patients undergoing general surgical procedures . The incidence of postoperative pain was significantly less in patients treated with coated polyglactin 910 suture with triclosan than the traditional suture . We speculate that polyglactin 910 suture with triclosan , by inhibiting bacterial colonization of the suture , reduced pain that can be an indicator of " sub clinical " infection . Coated polyglactin 910 suture with triclosan may be a useful alternative in patients at increased risk of developing SSI BACKGROUND Wound infection and dehiscence are both major contributors to postoperative morbidity . One potential cause or co-factor is the use of suture material . A recently introduced subcutaneous suture is coated with triclosan ( TC ) , an antiseptic drug . It is suggested to reduce wound complications . METHODS To investigate the effect of TC on wound healing a double blind prospect i ve pilot study in women undergoing a breast reduction was performed . Each patient was her own control . After r and omisation the TC-coated sutures were used either on the left or right side . The contralateral side was used as the control . The incidence of dehiscence was studied . RESULTS Twenty-six patients were included . In the TC breasts there was a wound dehiscence in 16 cases , whereas in the control breasts in seven cases a dehiscence was observed ( P=0.023 ) . CONCLUSION These results suggest that TC-coated sutures should be used with caution . These sutures have already been introduced on to the market without good clinical studies and might have potential adverse effects as shown by these data BACKGROUND In colorectal surgeries , surgical site infections ( SSIs ) frequently cause morbidity ; an incidence of up to 20 % has been shown in previous studies . Recently , to prevent microbial colonization of suture material in operative wounds , triclosan-coated polyglactin suture material s with antimicrobial activity have been developed ; however , their significance in colorectal surgery remains unclear . This r and omized controlled trial was conducted to assess the value of triclosan-coated polyglactin sutures in colorectal surgery . METHODS A total of 410 consecutive patients who had undergone elective colorectal operations were enrolled in this trial . Of those patients , the 206 in the study group underwent wound closure with triclosan-coated polyglactin 910 antimicrobial sutures , and the 204 patients in the control group received conventional wound closures with polyglactin 910 sutures . RESULTS The study group and the control group were comparable regarding risk factors for SSIs . The incidence of wound infection in the study group was 9 of 206 patients ( 4.3 % ) , and that in the control group was 19 of 204 patients ( 9.3 % ) . The difference is statistically significant in the 2 groups ( P = .047 ) . The median additional cost of wound infection management was $ 2,310 . The actual entire additional cost , therefore , of 9 patients in the study group was $ 18,370 , and that of 19 patients in the control group was $ 60,814 . CONCLUSION Triclosan-coated sutures can reduce the incidence of wound infections and the costs in colorectal surgery 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 Surgical wound infection ( SWI ) is a common complication after peripheral vascular surgery . In a prospect i ve study , triclosan-coated sutures were reported to decrease the incidence of surgical site infection after various surgical procedures . The aim of our study was to test the hypothesis that use of triclosan-coated sutures decreases the incidence of SWI after lower limb vascular surgery . Methods This prospect i ve , r and omized , multicenter , double-blinded trial was conducted between July 2010 and January 2011 in five hospitals in Finl and . We r and omly allocated 276 patients undergoing lower limb revascularization surgery to a study ( n = 139 ) or a control ( n = 137 ) group . Surgical wounds in the study group were closed with triclosan-coated suture material , and wounds in the control group were closed with noncoated sutures . The main outcome measure was SWI . A surgical wound complication was considered to be an infection if there were bacteria isolated from the wound or if there were areas of localized redness , heat , swelling , and pain around the wound appearing within 30 days after the operative procedure . Logistic regression analysis was used to assess the independent effect of triclosan-coated sutures on the incidence of SWI . Results Altogether , 61 ( 22.1 % ) patients developed SWI . SWI occurred in 31 ( 22.3 % ) patients in the study group and in 30 ( 21.9 % ) patients in the control group ( odds ratio 1.10 , 95 % confidence interval 0.61–2.01 , p = 0.75 . ) Conclusions The use of triclosan-coated sutures does not reduce the incidence of SWI after lower limb vascular surgery The reconstruction of abdominal wall defects remains a huge surgical challenge . Tension-free repair is proven to be superior to suture repair in abdominal wall reconstruction . Scaffolds are essential for tension-free repair . They are used to bridge a defect or reinforce the abdominal wall . A huge variety of scaffolds are now commercially available . Most of the synthetic scaffolds are composed of polypropylene . They provide strong tissue reinforcement , but cause a foreign body reaction , which can result in serious complications . Absorbable synthetic scaffolds , such as Dexon ™ ( polyglycolic acid ) and Vicryl ™ ( polyglactin 910 ) , are not suitable for abdominal wall reconstruction as they usually require subsequent surgeries to repair recurrent hernias . Composite scaffolds combine the strength of nonabsorbable synthetic scaffolds with the antiadhesive properties of the absorbable scaffold , but require long-term follow-up . Biological scaffolds , such as Permacol ™ , Surgisis ® and Alloderm ® , are derived from acellular mammalian tissues . Non-cross-linked biological scaffolds show excellent biocompatibility and de grade slowly over time . However , remnant DNA has been found in several products and the degradation leads to recurrence . R and omized controlled trials with long-term follow-up studies are lacking for all of the available scaffolds , particularly those derived from animal tissue . This article provides an overview of the different types of scaffolds available , and presents the key clinical studies of the commercially available synthetic , composite and biological scaffolds for abdominal wall reconstruction BACKGROUND Surgical site infections ( SSI ) are the third most common hospital-acquired infections and account for 14 % to 16 % of all such infections . In elective colorectal operations , the international SSI rate ranges from 4.7%-25 % . In a previous retrospective study in this department , the SSI rate was unacceptably high ( 25 % ) , and the promising different international evaluations of triclosan-coated suture material s encouraged us to create a multicenter r and omized trial to improve our results . The main goal of this study was to compare triclosan-coated and uncoated absorbable suture ( PDS Plus ( ® ) with PDS II ( ® ) ) in elective colorectal operations . METHODS This was an internet-based study involving seven surgical centers . All the elective colorectal operations were performed by experienced surgeons . For abdominal fascia closure , running looped PDS was applied ; triclosan-coated or uncoated PDS was chosen by computer r and omization . Pre-operative and peri-operative variables such as gender , body mass index , neoadjuvant therapy , type II diabetes mellitus , amount of wound dressing material used , nursing days , and microbiological results were recorded . After the operation , the patient 's data and risk factors were collected in a password-protected online data base . RESULTS From 485 patients r and omized , SSI was documented in 47 patients ( 12.5 % ) , 23 ( 12.2 % ) in the group having triclosan-coated sutures ( n=188 ) and 24 ( 12.2 % ) in the uncoated suture group ( n=197 ) , a non-significant difference . Of all SSIs , 13 ( 27.7 % ) were diagnosed only after discharge , being recognized in the outpatient setting , with four patients in the triclosan suture group ( 8.5 % ) and nine in the uncoated suture group ( 19.2 % ) being affected with no significant differences in the demographic data . Microbiological examinations , in addition to the same colon flora in both groups , revealed two gram-positive infections in the uncoated suture group . The hospital stay and costs of dressings were significantly higher in patients having SSIs . CONCLUSION Compared with the previous retrospective studies of this department , the implementation of looped PDS decreased the incidence of SSI by one-half , whether the suture was triclosan-coated or not . It seems that patient factors are less important than operative factors in the occurrence of SSI , and there were no differences between elective colon and rectal operations in the development of incisional infections . No beneficial effect of triclosan against gram-positive bacteria , which has been reported in the literature , could be confirmed in our study . We could not show an effect against gram-negative enteric microorganisms . Higher additional costs and longer hospital stay with SSI were confirmed BACKGROUND Wound infections after abdominal surgery are still frequent types of nosocomial infections . Suture material s might serve as a vehicle for mechanical transport of bacteria into the surgical wound . To prevent the contamination of suture material in surgical wounds , triclosan-coated suture material s with antibacterial activity was developed . We here report a prospect i ve r and omized pathway controlled trial investigating the effect of triclosan impregnation of polydioxanone sutures used for abdominal wall closure on the rate of surgical-site infections . PATIENTS AND METHODS A total of 856 patients included in this trial underwent a st and ardized clinical pathway documented abdominal wall closure after abdominal surgery . Patients were r and omized to have the fascia closed with either a 2 - 0 polydioxanone loop or a triclosan impregnated 2 - 0 polydioxanone loop . The primary outcome was the number of wound infections . Risk factors for poor wound healing were collected prospect ively to compare the two groups . RESULTS When a PDS loop suture for abdominal wall closure was used , 42 ( 11.3 % ) patients with wound infections were detected . The number of patients with wound infections decreased significantly to 31 when the PDS plus for abdominal wall closure was used ( 6.4 % , P < .05 ) . Other risk factors for the development of side infections were comparably in the two groups . CONCLUSION This clinical pathway facilitated trial shows that triclosan impregnation of a 2 - 0 polydioxanone closing suture can decrease wound infections in patients having a laparotomy for general and abdominal vascular procedures BACKGROUND Surgical site infection is a common complication of surgery . Its morbidities range from delayed healing to systemic sepsis . It has impact on the economy and health care re sources . METHODS This study was a prospect i ve , r and omized , double-blinded , controlled multicenter study aim ed to compare triclosan-coated polyglactin 910 sutures with polyglactin 910 sutures for the reduction of surgical site infections . This article details the results from the Cairo University center . A total of 450 patients who had undergone different surgical procedures were enrolled ; 230 were enrolled in the study group and 220 were enrolled in the control group . RESULTS The study group and the control group were comparable regarding risk factors for surgical site infection . Surgical site infection incidence was 7 % in the study group and 15 % in the control group ( P = .011 ) . The mean extended stay as a result of infection was 3.71 days , with an average cost $ 91 US per day . CONCLUSIONS Use of the triclosan-coated polyglactin 910 antimicrobial suture lead to reduction of surgical site infection and has an impact on saving health care re sources . The triclosan-coated polyglactin 910 antimicrobial suture could save $ 1,517,727 yearly in this single center |
10,315 | 26,828,647 | RESULTS The cost-effectiveness for prostate cancer-the single most common diagnosis currently treated with PBT-was suboptimal .
PBT was the most cost-effective option for several pediatric brain tumors .
PBT costs for breast cancer were increased but were favorable for appropriately selected patients with left-sided cancers at high risk of cardiac toxicity and compared with brachytherapy for accelerated partial breast irradiation .
For non-small cell lung cancer ( NSCLC ) , the greatest cost-effectiveness benefits using PBT were observed for locoregionally advanced-but not early stage-tumors .
PBT offered superior cost-effectiveness in selected head/neck cancer patients at higher risk of acute mucosal toxicities .
Similar cost-effectiveness was observed for PBT , enucleation , and plaque brachytherapy in patients with uveal melanoma .
With greatly limited amounts of data , PBT offers promising cost-effectiveness for pediatric brain tumors , well-selected breast cancers , locoregionally advanced NSCLC , and high-risk head/neck cancers .
Heretofore , it has not been demonstrated that PBT is cost-effective for prostate cancer or early stage NSCLC . | BACKGROUND Economic analyses of new technologies , such as proton-beam radiotherapy ( PBT ) , are a public health priority .
To date , no systematic review of the cost-effectiveness of PBT has been performed . | PURPOSE The unique dosimetric features of proton radiotherapy make it an attractive modality for normal tissue sparing . We present our initial experience with protons for three-dimensional , conformal , external-beam accelerated partial breast irradiation ( 3D-CPBI ) . METHODS AND MATERIAL S From March 2004 to June 2005 , 25 patients with tumors < or = 2 cm and negative axillary nodes were treated with proton 3D-CPBI . The prescribed dose was 32 Cobalt Gray Equivalents ( CGE ) in 4 CGE fractions given twice daily . One to three fields were used to provide adequate planning target volume ( PTV ) coverage and dose homogeneity . RESULTS Excellent PTV coverage and dose homogeneity were obtained in all patients with one to three proton beams . The median PTV receiving 95 % of the prescribed dose was 100 % . Dose inhomogeneity exceeded 10 % in only 1 patient ( 4 % ) . The median volume of nontarget breast tissue receiving 50 % of the prescribed dose was 23 % . Median volumes of ipsilateral lung receiving 20 CGE , 10 CGE , and 5 CGE were 0 % , 1 % , and 2 % , respectively . The contralateral lung and heart received essentially no radiation dose . Cost analysis suggests that proton 3D-CPBI is only modestly more expensive ( 25 % ) than traditional whole-breast irradiation ( WBI ) . CONCLUSION Proton 3D-CPBI is technically feasible , providing both excellent PTV coverage and normal tissue sparing . It markedly reduces the volume of nontarget breast tissue irradiated compared with photon-based 3D-CPBI , addressing a principle disadvantage of external-beam approaches to PBI . As proton therapy becomes more widely available , it may prove an attractive tool for 3D-CPBI BACKGROUND Radiotherapy can impair Health Related Quality of Life ( HRQoL ) in survivors of childhood brain tumors , but proton radiotherapy ( PRT ) may mitigate this effect . This study compares HRQoL in PRT and photon ( XRT ) pediatric brain tumor survivors . METHODS HRQoL data were prospect ively collected on PRT-treated patients aged 2 - 18 treated at Massachusetts General Hospital ( MGH ) . Cross-sectional PedsQL data from XRT treated Lucile Packard Children 's Hospital ( LPCH ) patients provided the comparison data . RESULTS Parent proxy HRQoL scores were reported at 3 years for the PRT cohort ( PRT-C ) and 2.9 years ( median ) for the XRT cohort ( XRT-C ) . The total core HRQoL score for the PRT-C , XRT-C , and normative population differed from one another and was 75.9 , 65.4 and 80.9 respectively ( p=0.002 ; p=0.024 ; p<0.001 ) . The PRT-C scored 10.3 and 10.5 points higher than the XRT-C in the physical ( PhSD ) and psychosocial ( PsSD ) summary domains of the total core score ( TCS , p=0.015 ; p=0.001 ) . The PRT-C showed no difference in PhSD compared with the normative population , but scored 6.1 points less in the PsSD ( p=0.003 ) . Compared to healthy controls , the XRT-C scored lower in all domains ( p<0.001 ) . CONCLUSIONS The HRQoL of pediatric brain tumor survivors treated with PRT compare favorably to those treated with XRT and similar to healthy controls in the PhSD OBJECTIVE To evaluate late ( more than 5 years ) radiation failures after uveal melanoma treatment . DESIGN Comparison of three retrospective , interventional , partially r and omized case series . PARTICIPANTS Nine hundred ninety-six patients who were treated in several phase I , II , and III trials of uveal melanoma radiation . MAIN OUTCOME MEASURES Follow-up period , treatment history , recurrence rates , type of recurrence , and mortality associated with late local recurrences . RESULTS Eleven of 996 irradiated uveal melanoma patients experienced intraocular recurrence more than 5 years after radiation . All 11 of these patients were treated with iodine 125 ( (125)I ) brachytherapy . Late recurrences were detected between 5.5 to 15.3 years after treatment . These patients did not have either high-risk clinical parameters ( thin , posterior tumors in proximity to the optic nerve ) or radiation dosimetry characteristics ( low dose-delivery radiation ) associated with a known increased risk for tumor recurrence after radioactive plaques . The annualized incidence rate for regrowth was 1.9 % per year between 5 and 15 years after (125)I brachytherapy . In contrast to charged particles , the risk of late recurrence after (125)I brachytherapy continued with increased follow-up . CONCLUSIONS There was a significantly higher late recurrence rate with (125)I brachytherapy as compared with charged particle radiation . Although tumor enlargement 5 or more years after radiation can be the result of intratumor hemorrhage , in a patient treated with radioactive plaque , a late failure is a distinct possibility PURPOSE Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy ( CPT ) programs . Here we report long-term outcomes from the only r and omized , stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma . METHODS AND MATERIAL S From 1985 to 1991 , 184 patients met eligibility criteria and were r and omized to receive particle ( 86 patients ) or plaque therapy ( 98 patients ) . Patients were stratified by tumor diameter , thickness , distance to disc/fovea , anterior extension , and visual acuity . Tumors close to the optic disc were included . Local tumor control , as well as eye preservation , metastases due to melanoma , and survival were evaluated . RESULTS Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years , respectively ( P=.22 ) , and for those alive at last follow-up , 18.5 and 16.5 years , respectively ( P=.81 ) . Local control ( LC ) for particle versus plaque treatment was 100 % versus 84 % at 5 years , and 98 % versus 79 % at 12 years , respectively ( log rank : P=.0006 ) . If patients with tumors close to the disc ( < 2 mm ) were excluded , CPT still result ed in significantly improved LC : 100 % versus 90 % at 5 years and 98 % versus 86 % at 12 years , respectively ( log rank : P=.048 ) . Enucleation rate was lower after CPT : 11 % versus 22 % at 5 years and 17 % versus 37 % at 12 years , respectively ( log rank : P=.01 ) . Using Cox regression model , likelihood ratio test , treatment was the most important predictor of LC ( P=.0002 ) and eye preservation ( P=.01 ) . CPT was a significant predictor of prolonged disease-free survival ( log rank : P=.001 ) . CONCLUSIONS Particle therapy result ed in significantly improved local control , eye preservation , and disease-free survival as confirmed by long-term outcomes from the only r and omized study available to date comparing radiation modalities in choroidal and ciliary body melanoma BACKGROUND We aim ed to compare overall survival after st and ard-dose versus high-dose conformal radiotherapy with concurrent chemotherapy and the addition of cetuximab to concurrent chemoradiation for patients with inoperable stage III non-small-cell lung cancer . METHODS In this open-label r and omised , two-by-two factorial phase 3 study in 185 institutions in the USA and Canada , we enrolled patients ( aged ≥ 18 years ) with unresectable stage III non-small-cell lung cancer , a Zubrod performance status of 0 - 1 , adequate pulmonary function , and no evidence of supraclavicular or contralateral hilar adenopathy . We r and omly assigned ( 1:1:1:1 ) patients to receive either 60 Gy ( st and ard dose ) , 74 Gy ( high dose ) , 60 Gy plus cetuximab , or 74 Gy plus cetuximab . All patients also received concurrent chemotherapy with 45 mg/m(2 ) paclitaxel and carboplatin once a week ( AUC 2 ) ; 2 weeks after chemoradiation , two cycles of consolidation chemotherapy separated by 3 weeks were given consisting of paclitaxel ( 200 mg/m(2 ) ) and carboplatin ( AUC 6 ) . R and omisation was done with permuted block r and omisation methods , stratified by radiotherapy technique , Zubrod performance status , use of PET during staging , and histology ; treatment group assignments were not masked . Radiation dose was prescribed to the planning target volume and was given in 2 Gy daily fractions with either intensity-modulated radiation therapy or three-dimensional conformal radiation therapy . The use of four-dimensional CT and image-guided radiation therapy were encouraged but not necessary . For patients assigned to receive cetuximab , 400 mg/m(2 ) cetuximab was given on day 1 followed by weekly doses of 250 mg/m(2 ) , and was continued through consolidation therapy . The primary endpoint was overall survival . All analyses were done by modified intention-to-treat . The study is registered with Clinical Trials.gov , number NCT00533949 . FINDINGS Between Nov 27 , 2007 , and Nov 22 , 2011 , 166 patients were r and omly assigned to receive st and ard-dose chemoradiotherapy , 121 to high-dose chemoradiotherapy , 147 to st and ard-dose chemoradiotherapy and cetuximab , and 110 to high-dose chemoradiotherapy and cetuximab . Median follow-up for the radiotherapy comparison was 22.9 months ( IQR 27.5 - 33.3 ) . Median overall survival was 28.7 months ( 95 % CI 24.1 - 36.9 ) for patients who received st and ard-dose radiotherapy and 20.3 months ( 17.7 - 25.0 ) for those who received high-dose radiotherapy ( hazard ratio [ HR ] 1.38 , 95 % CI 1.09 - 1.76 ; p=0.004 ) . Median follow-up for the cetuximab comparison was 21.3 months ( IQR 23.5 - 29.8 ) . Median overall survival in patients who received cetuximab was 25.0 months ( 95 % CI 20.2 - 30.5 ) compared with 24.0 months ( 19.8 - 28.6 ) in those who did not ( HR 1.07 , 95 % CI 0.84 - 1.35 ; p=0.29 ) . Both the radiation-dose and cetuximab results crossed protocol -specified futility boundaries . We recorded no statistical differences in grade 3 or worse toxic effects between radiotherapy groups . By contrast , the use of cetuximab was associated with a higher rate of grade 3 or worse toxic effects ( 205 [ 86 % ] of 237 vs 160 [ 70 % ] of 228 patients ; p<0.0001 ) . There were more treatment-related deaths in the high-dose chemoradiotherapy and cetuximab groups ( radiotherapy comparison : eight vs three patients ; cetuximab comparison : ten vs five patients ) . There were no differences in severe pulmonary events between treatment groups . Severe oesophagitis was more common in patients who received high-dose chemoradiotherapy than in those who received st and ard-dose treatment ( 43 [ 21 % ] of 207 patients vs 16 [ 7 % ] of 217 patients ; p<0.0001 ) . INTERPRETATION 74 Gy radiation given in 2 Gy fractions with concurrent chemotherapy was not better than 60 Gy plus concurrent chemotherapy for patients with stage III non-small-cell lung cancer , and might be potentially harmful . Addition of cetuximab to concurrent chemoradiation and consolidation treatment provided no benefit in overall survival for these patients . FUNDING National Cancer Institute and Bristol-Myers Squibb COMMENTARY Recently , mature data were published from the MA.20 and European Organization for the Research and Treatment of Cancer ( EORTC ) 22922 trials , providing clinicians with increasing data supporting the value of regional nodal irradiation ( RNI ) . The MA.20 r and omized 1832 women with highrisk node-negative ( T3 , T2 with < 10 nodes removed and grade 3/estrogen receptor-negative/lymphovascular space invasion ) or node-positive disease to receive whole breast irradiation with or without RNI ( axillary apex , internal mammary , supraclavicular ) with > 80 % of patients having 1 to 3 nodes positive . Ten-year outcomes demonstrated an improvement in disease-free survival ( 82 % vs. 77 % ) with reductions in distant metastases and locoregional recurrences with the addition of RNI with modest increases in pneumonitis ( 1.2 % vs. 0.2 % ) and lymphedema ( 8.4 % vs. 4.5 % ) . Similarly , the EORTC trial r and omized 4004 women with centromedial tumors or lateral tumors with axillary disease to receive radiation with or without inclusion of the internal mammary chain and medial supraclavicular nodes ; 43 % of patients had 1 to 3 nodes involved . Results of the study demonstrated improvements in disease-free survival ( 72 % vs. 69 % ) , distant metastases-free survival , and reductions in breast cancer mortality with a trend for improved overall survival . These results confirm data from previous studies ( subset analyses of postmastectomy r and omized trials , meta-analyses ) that demonstrated improvement in outcomes with radiation therapy ( including RNI ) for patients with 1 to 3 nodes positive . Recent commentary following the publication of these studies has question ed the role of RNI despite the aforementioned improvements in disease-free survival , distant metastases , and locoregional control due to a lack of survival benefit in these trials . However , it should be noted that improvements in locoregional control , disease-free survival , distant metastases , and breast cancer mortality have justified the utilization of surgical , systemic , and radiotherapeutic techniques in the past and continue to do so . For instance , the National Surgical Adjuvant Breast and Bowel Project B28 trial has result ed in the widespread addition of taxanes to anthracycline-based chemotherapy , and the Cancer and Leukemia Group B 9741 results result ed in increasing utilization of dose-dense chemotherapy regimens despite lower than expected outcome events . Further , the EORTC trial demonstrated a trend for improvement in overall survival with the potential for improved survival with further follow-up . Arguments for limiting RNI presented include a reduction in the rates of local recurrence , improvements in systemic therapy , and differences in nodal sampling compared with recent studies . With regards to the improvement in locoregional control over time , recent data demonstrate locoregional recurrence rates exceeding 10 % in patients even in patients with low-volume nodal disease with modern systemic therapy . Systemic therapy has evolved over the past few decades ; however , taxanes were utilized in these studies ( 26 % in MA.20 ; unknown in EORTC 22922 ) and limited data are available suggesting an improvement in locoregional control with trastuzumab , with the benefit more likely associated with radiotherapy . Similarly , aromatase inhibitors have demonstrated a reduction in recurrences but these were primarily distant recurrences and contralateral breast cancers rather than local recurrences . Although management of the axilla continues to evolve , there is insufficient evidence to support that the results of the American College of Surgeons Oncology Group Z011 and After Mapping Axilla , Radiotherapy or Surgery trials is from systemic therapy and in the case of the After Mapping Axilla , Radiotherapy or Surgery trial is more likely due to the RNI . Similarly , although there is a difference in the number of nodes sample d ( 12 to 15 vs. 17 ) , there is insufficient evidence to support that this difference would lead to a difference in the clinical outcomes noted . RNI can be associated with toxicity though the rates remain low ; the EORTC trial demonstrated an increase in pulmonary fibrosis although it was < 5 % with no difference in other late toxicities . Similarly , MA.20 demonstrated a small increase in pneumonitis as well as chronic lymphedema and skin changes . However , the cost-benefit of an improvement in disease-free survival and potentially overall survival with longer follow-up outweighs the small increase in toxicity . There is a concern regarding the heterogeneity of these trials . A recent editorial recommended RNI for those with Z4 nodes positive but suggested that RNI be limited in patients with 1 to 3 nodes positive to those with high-risk From the * Department of Radiation Oncology , Clevel and Clinic , Taussig Cancer Institute , Clevel and ; wDepartment of Radiation Oncology , Northeast Ohio Medical University , Rootstown , OH ; zDepartment of Radiation Oncology , Rutgers Robert Wood Johnson Medical School , Cancer Institute of New Jersey , New Brunswick , NJ ; yDepartment of Radiation Oncology , Massey Cancer Center , Virgina Commonwealth University , Richmond , VA ; 8Tufts University School of Medicine , Boston , MA ; zAlpert Medical School of Brown University , Providence , RI ; # 21st Century Oncology , Fort Myers , FL ; * * Department of Radiation Oncology , University of Nebraska Medical Center , Omaha , NE ; and wwMichigan Healthcare Professionals/21st Century Oncology , Farmington Hills , MI . The authors declare no conflicts of interest . Reprints : Chirag Shah , MD , Department of Radiation Oncology , Clevel and Clinic , Taussig Cancer Institute , 9500 Euclid Avenue , Clevel and , OH 44195 . E-mail : [email protected] . Copyright r 2015 Wolters Kluwer Health , Inc. All rights reserved . ISSN : 0277 - 3732/16/3901 - 0090 DOI : 10.1097/COC.0000000000000250 CANCER MANAGEMENT PURPOSE This prospect i ve phase II study was design ed to assess disease control and to describe acute and late adverse effects of treatment with proton radiotherapy in children with rhabdomyosarcoma ( RMS ) . PATIENTS AND METHODS Fifty-seven patients with localized RMS ( age 21 years or younger ) or metastatic embryonal RMS ( age 2 to 10 years ) were enrolled between February 2005 and August 2012 . All patients were treated with chemotherapy based on either vincristine , actinomycin , and cyclophosphamide or vincristine , actinomycin , and ifosfamide-based chemotherapy and proton radiation . Surgical resection was based on tumor site and accessibility . Common Terminology Criteria for Adverse Events , Version 3.0 , was used to assess and grade adverse effects of treatment . Concurrent enrollment onto Children 's Oncology Group or European Pediatric Sarcoma Study Group protocol s was allowed . All pathology and imaging were review ed at the treating institution . RESULTS Median follow-up was 47 months ( range , 14 to 102 months ) for survivors . Five-year event-free survival ( EFS ) , overall survival ( OS ) , and local control ( LC ) were 69 % , 78 % , and 81 % , respectively , for the entire cohort . The 5-year LC by risk group was 93 % for low-risk and 77 % for intermediate-risk disease . There were 13 patients with grade 3 acute toxicity and three patients with grade 3 late toxicity . There were no acute or late toxicities higher than grade 3 . CONCLUSION Five-year LC , EFS , and OS rates were similar to those observed in comparable trials that used photon radiation . Acute and late toxicity rates were favorable . Proton radiation appears to represent a safe and effective radiation modality for pediatric RMS |
10,316 | 25,800,534 | It was concluded that the use of diode LLLT for orthodontic pain appears promising .
However , due to method ological weaknesses , there was insufficient evidence to support or refute LLLT ’s effectiveness . | null | null |
10,317 | 24,864,163 | The type and frequency of bevacizumab-related adverse events was as expected in these studies based on published data .
Promising efficacy data have been published for a number of emerging anti-angiogenic agents in phase III development for advanced ovarian cancer . | As increased angiogenesis has been linked with the progression of ovarian cancer , a number of anti-angiogenic agents have been investigated , or are currently in development , as potential treatment options for patients with advanced disease .
Bevacizumab , a recombinant monoclonal antibody against vascular endothelial growth factor , has gained European Medicines Agency approval for the front-line treatment of advanced epithelial ovarian cancer , fallopian tube cancer or primary peritoneal cancer in combination with carboplatin and paclitaxel , and for the treatment of first recurrence of platinum-sensitive ovarian cancer in combination with carboplatin and gemcitabine .
We conducted a systematic literature review to identify available efficacy and safety data for bevacizumab in ovarian cancer as well as for newer anti-angiogenic agents in development . | BACKGROUND Angiogenesis plays a role in the biology of ovarian cancer . We examined the effect of bevacizumab , the vascular endothelial growth factor inhibitor , on survival in women with this disease . METHODS We r and omly assigned women with ovarian cancer to carboplatin ( area under the curve , 5 or 6 ) and paclitaxel ( 175 mg per square meter of body-surface area ) , given every 3 weeks for 6 cycles , or to this regimen plus bevacizumab ( 7.5 mg per kilogram of body weight ) , given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until progression of disease . Outcome measures included progression-free survival , first analyzed per protocol and then up date d , and interim overall survival . RESULTS A total of 1528 women from 11 countries were r and omly assigned to one of the two treatment regimens . Their median age was 57 years ; 90 % had epithelial ovarian cancer , 69 % had a serous histologic type , 9 % had high-risk early-stage disease , 30 % were at high risk for progression , and 70 % had stage IIIC or IV ovarian cancer . Progression-free survival ( restricted mean ) at 36 months was 20.3 months with st and ard therapy , as compared with 21.8 months with st and ard therapy plus bevacizumab ( hazard ratio for progression or death with bevacizumab added , 0.81 ; 95 % confidence interval , 0.70 to 0.94 ; P=0.004 by the log-rank test ) . Nonproportional hazards were detected ( i.e. , the treatment effect was not consistent over time on the hazard function scale ) ( P<0.001 ) , with a maximum effect at 12 months , coinciding with the end of planned bevacizumab treatment and diminishing by 24 months . Bevacizumab was associated with more toxic effects ( most often hypertension of grade 2 or higher ) ( 18 % , vs. 2 % with chemotherapy alone ) . In the up date d analyses , progression-free survival ( restricted mean ) at 42 months was 22.4 months without bevacizumab versus 24.1 months with bevacizumab ( P=0.04 by log-rank test ) ; in patients at high risk for progression , the benefit was greater with bevacizumab than without it , with progression-free survival ( restricted mean ) at 42 months of 14.5 months with st and ard therapy alone and 18.1 months with bevacizumab added , with respective median overall survival of 28.8 and 36.6 months . CONCLUSIONS Bevacizumab improved progression-free survival in women with ovarian cancer . The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression . ( Funded by Roche and others ; ICON7 Controlled-Trials.com number , IS RCT N91273375 . ) BACKGROUND Targeting of VEGF is a potential therapeutic option in patients with malignant ovarian ascites . We present the final results of a multicentre study of the efficacy and safety of aflibercept , a potent inhibitor of both VEGF and placental growth factor , in the treatment of malignant ascites . METHODS In this double-blind , placebo-controlled , parallel-group , phase 2 study , patients with advanced chemoresistant ovarian cancer and recurrent symptomatic malignant ascites were r and omly assigned ( 1:1 ) via an interactive voice response system to either intravenous aflibercept ( 4 mg/kg every 2 weeks ) or placebo , stratified by interval of time ( ≤ 2 weeks vs > 2 weeks ) between the two most recent paracenteses before r and omisation . Patients participated in the double-blind period ( during which patients , investigators , and sponsor personnel were masked to treatment assignment ) until they had a repeat paracentesis and for at least 60 days , and could also participate in an optional open-label period during which all patients received aflibercept . The primary efficacy endpoint was time to repeat paracentesis based on response during the double-blind period alone , and was analysed in the intention-to-treat population with censoring of patients who did not have a repeat paracentesis as of the last day of the double-blind period . Safety analyses included both double-blind and open-label periods . This study is registered at Clinical Trials.gov , number NCT00327444 . FINDINGS 55 patients with a median of four ( range two to 11 ) previous lines of chemotherapy were r and omly assigned to receive placebo ( n=26 ) or aflibercept ( n=29 ) . Mean time to repeat paracentesis was significantly longer with aflibercept than with placebo ( 55·1 [ SE 7·3 ] vs 23·3 [ 7·7 ] days ; difference 31·8 days , 95 % CI 10·6 - 53·1 ; p=0·0019 ) . In the aflibercept group , two patients did not need a repeat paracentesis during 6 months of double-blind treatment . The most common grade 3 or 4 treatment-emergent adverse events were dyspnoea ( six [ 20 % ] aflibercept vs two [ 8 % ] placebo ) , fatigue or asthenia ( four [ 13 % ] vs 11 [ 44 % ] ) , and dehydration ( three [ 10 % ] vs three [ 12 % ] ) . The frequency of fatal gastrointestinal events was higher with aflibercept ( three intestinal perforations ) than with placebo ( one intestinal fistula leading to sepsis ) . INTERPRETATION This study shows the effectiveness of VEGF blockade in the reduction of malignant ascites , but confirms the significant clinical risk of fatal bowel perforation in this population of patients with very advanced cancer . VEGF blockade should be used with caution in advanced ovarian cancer with abdominal carcinomatosis , and the benefit-risk balance should be thoroughly discussed for each patient . FUNDING Sanofi Oncology PURPOSE This r and omized , multicenter , blinded , placebo-controlled phase III trial tested the efficacy and safety of bevacizumab ( BV ) with gemcitabine and carboplatin ( GC ) compared with GC in platinum-sensitive recurrent ovarian , primary peritoneal , or fallopian tube cancer ( ROC ) . PATIENTS AND METHODS Patients with platinum-sensitive ROC ( recurrence ≥ 6 months after front-line platinum-based therapy ) and measurable disease were r and omly assigned to GC plus either BV or placebo ( PL ) for six to 10 cycles . BV or PL , respectively , was then continued until disease progression . The primary end point was progression-free survival ( PFS ) by RECIST ; secondary end points were objective response rate , duration of response ( DOR ) , overall survival , and safety . RESULTS Overall , 484 patients were r and omly assigned . PFS for the BV arm was superior to that for the PL arm ( hazard ratio [ HR ] , 0.484 ; 95 % CI , 0.388 to 0.605 ; log-rank P < .0001 ) ; median PFS was 12.4 v 8.4 months , respectively . The objective response rate ( 78.5 % v 57.4 % ; P < .0001 ) and DOR ( 10.4 v 7.4 months ; HR , 0.534 ; 95 % CI , 0.408 to 0.698 ) were significantly improved with the addition of BV . No new safety concerns were noted . Grade 3 or higher hypertension ( 17.4 % v < 1 % ) and proteinuria ( 8.5 % v < 1 % ) occurred more frequently in the BV arm . The rates of neutropenia and febrile neutropenia were similar in both arms . Two patients in the BV arm experienced GI perforation after study treatment discontinuation . CONCLUSION GC plus BV followed by BV until progression result ed in a statistically significant improvement in PFS compared with GC plus PL in platinum-sensitive ROC PURPOSE Inhibiting angiogenesis is one of the most promising avenues for new therapies for ovarian cancer . We investigated the efficacy and safety of a novel agent , BIBF 1120 , a triple angiokinase inhibitor , after chemotherapy for relapsed disease . PATIENTS AND METHODS We conducted a r and omized , double-blind , controlled phase II trial in 83 patients who had just completed chemotherapy for relapsed ovarian cancer , with evidence of response , but at high risk of further early recurrence . The patients were r and omly assigned to receive maintenance therapy using BIBF 1120 250 mg or placebo , twice per day , continuously for 36 weeks . End points were progression-free survival ( PFS ) , toxicity , and overall survival . RESULTS Thirty-six-week PFS rates were 16.3 % and 5.0 % in the BIBF 1120 and placebo groups , respectively ( hazard ratio , 0.65 ; 95 % CI , 0.42 to 1.02 ; P = .06 ) . Four patients continued on BIBF 1120 , including two patients for another year or more . The proportion of patients with any grade 3 or 4 adverse events was similar between the groups ( 34.9 % for BIBF 1120 v 27.5 % for placebo ; P = .49 ; mostly grade 3 ) . However , more patients on BIBF 1120 experienced diarrhea , nausea , or vomiting ( mainly grade 1 or 2 and no grade 4 ) . There was a higher rate of grade 3 or 4 hepatotoxicity in patients on BIBF 1120 ( 51.2 % ) compared with patients on placebo ( 7.5 % ; P < .001 ) , but this was rarely of clinical significance , and patients continued with the trial treatment . A single-level dose reduction to 150 mg was made in 15 patients , all on active drug . CONCLUSION BIBF 1120 is well tolerated and associated with a potential improvement in PFS . The observed treatment effect is sufficient to justify further study within a large phase III trial Purpose : This phase II trial evaluated bevacizumab plus erlotinib in platinum-resistant ovarian cancer ; exploratory biomarker analyses , including that of tumor vascular endothelial growth factor A ( VEGF-A ) , were also done . Experimental Design : Forty heavily pretreated patients received erlotinib ( 150 mg/d orally ) and bevacizumab ( 10 mg/kg i.v . ) every 2 weeks until disease progression . Primary end points were objective response rate and response duration ; secondary end points included progression-free survival ( PFS ) , toxicity , and correlations between angiogenic protein levels , toxicity , and efficacy . Results : Grade 3 toxicities included skin rash ( n = 6 ) , diarrhea ( n = 5 ) , fatigue ( n = 4 ) , and hypertension ( n = 3 ) . Grade 4 toxicities were myocardial infa rct ion ( n = 1 ) and nasal septal perforation ( n = 1 ) . Only one grade 3 fistula and one grade 2 bowel perforation were observed . Nine ( 23.1 % ) of 39 evaluable patients had a response ( median duration , 36.1 + weeks ; one complete response ) , and 10 ( 25.6 % ) patients achieved stable disease , for a disease control rate of 49 % . Median PFS was 4 months , and 6-month PFS was 30.8 % . Biomarker analyses identified an association between tumor cell VEGF-A expression and progression ( P = 0.03 ) ; for every 100-unit increase in the VEGF-A score , there was a 3.7-fold increase in the odds of progression ( 95 % confidence interval , 1.1 - 16.6 ) . Conclusions : Bevacizumab plus erlotinib in heavily pretreated ovarian cancer patients was clinical ly active and well tolerated . Erlotinib did not seem to contribute to efficacy . Our study raises the intriguing possibility that high levels of tumor cell VEGF-A , capable of both autocrine and paracrine interactions , are associated with resistance to bevacizumab , emphasizing the complexity of the tumor microenvironment . Clin Cancer Res ; 16(21 ) ; 5320–8 . © 2010 AACR BACKGROUND Recurrent platinum-resistant ovarian cancer usually has a poor outcome with conventional chemotherapeutic therapy and new treatment modalities are warranted . This phase II study was conducted to evaluate sunitinib , an oral antiangiogenic multitargeted tyrosin kinase inhibitor , in this setting . MATERIAL AND METHODS The primary end point of this r and omized phase II trial was the objective response rate according to RECIST criteria and /or Gynecologic Cancer InterGroup CA125 response criteria to sunitinib in patients with recurrent platinum-resistant ovarian cancer who were pretreated with up to three chemotherapies . A selection design was employed to compare two schedules of sunitinib ( arm 1 : 50 mg sunitinib daily orally for 28 days followed by 14 days off drug ; and arm 2 : 37.5 mg sunitinib administered daily continuously ) . RESULTS Of 73 patients enrolled , 36 patients were r and omly allocated to the noncontinuous treatment arm ( arm 1 ) and 37 patients were r and omly allocated to the continuous treatment arm ( arm 2 ) . The mean age was 58.8 and 58.5 years , respectively . We observed six responders ( complete response + partial response ) in arm 1 ( 16.7 % ) and 2 responders in arm 2 ( 5.4 % ) . The median progression-free survival ( arm 1 : 4.8 [ 2.9 - 8.1 ] months ; arm 2 : 2.9 [ 2.9 - 5.1 ] months ) and the median overall survival ( arm 1 : 13.6 [ 7.0 - 23.2 ] months ; arm 2 : 13.7 [ 8.4 - 25.6 ] months ) revealed no significant difference . Adverse events included fatigue as well as cardiovascular , gastrointestinal and abdominal symptoms , hematologic and hepatic laboratory abnormalities . Pattern and frequency of adverse events revealed no substantial differences between both treatment groups . CONCLUSIONS Sunitinib treatment is feasible and moderately active in relapsed platinum-resistant ovarian cancer . The noncontinuous treatment schedule should be chosen for further studies in ovarian cancer This trial compared the efficacy and toxicity of st and ard first‐line treatment with paclitaxel/carboplatin versus paclitaxel/carboplatin plus sorafenib in patients with advanced ovarian carcinoma . Patients with stage 3 or 4 epithelial ovarian cancer with residual measurable disease or elevated CA‐125 levels after maximal surgical cytoreduction were r and omized ( 1:1 ) to receive treatment with paclitaxel ( 175 mg/m2 , 3 h infusion , day 1 ) and carboplatin ( AUC 6.0 , IV , day 1 ) with or without sorafenib 400 mg orally twice daily ( PO BID ) . Patients were reevaluated for response after completing 6 weeks of treatment ( two cycles ) ; responding or stable patients received six cycles of paclitaxel/carboplatin . Patients receiving the sorafenib‐containing regimen continued sorafenib ( 400 PO BID ) for a total of 52 weeks . Eighty‐five patients were r and omized and received treatment . Efficacy was similar for patients receiving paclitaxel/carboplatin/sorafenib versus paclitaxel/carboplatin : overall response rates 69 % versus 74 % ; median progression‐free survival 15.4 versus 16.3 months ; 2 year survival 76 % versus 81 % . The addition of sorafenib added substantially to the toxicity of the regimen ; rash , h and –foot syndrome , mucositis , and hypertension were significantly more common in patients treated with sorafenib . The addition of sorafenib to st and ard paclitaxel/carboplatin did not improve efficacy and substantially increased toxicity in the first‐line treatment of advanced epithelial ovarian cancer . Based on evidence from this study and other completed trials , sorafenib is unlikely to have a role in the treatment of ovarian cancer Summary Background In the Gynecologic Cancer Intergroup International Collaboration on Ovarian Neoplasms 7 ( ICON7 ) trial , bevacizumab improved progression-free survival in patients with ovarian cancer when used in combination with first-line chemotherapy and as a single-drug continuation treatment for 18 cycles . In a preliminary analysis of a high-risk subset of patients , there was also an improvement in overall survival . This study aims to describe the health-related quality -of-life ( QoL ) outcomes from ICON7 . Methods ICON7 is a r and omised , multicentre , open-label phase 3 trial . Between Dec 18 , 2006 , and Feb 16 , 2009 , after a surgical procedure aim ing to debulk the disease , women with International Federation of Gynecology and Obstetrics ( FIGO ) high-risk stage I – IV epithelial ovarian cancer were r and omly allocated ( 1:1 ) by computer program and block r and omisation to receive either six cycles of st and ard chemotherapy ( total 18 weeks ) with carboplatin ( area under the curve 5 or 6 ) and paclitaxel ( 175 mg/m2 ) alone or with bevacizumab ( 7·5 mg/kg ) given intravenously with chemotherapy and continued as a single drug thereafter ( total 54 weeks ) . The primary QoL endpoint was global QoL from the European Organisation for Research and Treatment of Cancer quality -of-life question naire – core 30 at week 54 , analysed by ANOVA and adjusted for baseline score . Analyses were by intention to treat . The ICON7 trial has completed recruitment and remains in follow-up . This study is registered , number IS RCT N91273375 . Findings 764 women were r and omly assigned to the st and ard chemotherapy group and 764 to the bevacizumab group . At baseline , 684 ( 90 % ) of women in the st and ard chemotherapy group and 691 ( 90 % ) of those in the bevacizumab group had completed QoL question naires . At week 54 , 502 ( 66 % ) women in the bevacizumab group and 388 ( 51 % ) women in the st and ard chemotherapy group provided QoL data . Overall , the mean global QoL score improved during chemotherapy by 7·2 points ( SD 24·4 ) when analysed for all women with data at baseline and week 18 . The mean global QoL score at 54 weeks was higher in the st and ard chemotherapy group than in the bevacizumab group ( 76·1 [ SD 18·2 ] vs 69·7 [ 19·1 ] points ; difference 6·4 points , 95 % CI 3·7–9·0 , p<0·0001 ) . Interpretation Bevacizumab continuation treatment seems to be associated with a small but clinical ly significant decrement in QoL compared with st and ard treatment for women with ovarian cancer . The trade-off between the prolongation of progression-free survival and the quality of that period of time needs to be considered in clinical practice when making treatment decisions . Funding Roche and the National Institute for Health Research through the UK National Cancer Research Network OBJECTIVE The recombinant fusion protein , aflibercept binds and neutralizes vascular endothelial growth factor ( VEGF ) A , B and placental growth factor ( PlGF ) . Aflibercept inhibits ascites formation and reduces tumor burden in an ovarian cancer model . This open-label , single-arm , multicenter phase II study assessed the efficacy and safety of aflibercept in patients with advanced chemo-resistant epithelial ovarian cancer and symptomatic malignant ascites . METHODS Patients who required ≥3 previous paracenteses at 1 - 4 paracenteses per month received intravenous aflibercept 4mg/kg every 2 weeks . The primary endpoint was repeat paracentesis response rate ( RPRR ) , with response defined as at least a two-fold increase in time to repeat paracentesis compared with the baseline interval . RESULTS Ten out of 16 enrolled patients achieved a response ; the RPRR was 62.5 % ( 95 % CI 35.4%-84.8 % ) . Aflibercept was considered effective based on a hypothesis that the RPRR was ≥60 % . Median time to repeat paracentesis was 76.0 ( 95 % CI 64.0 - 178.0 ) days , which was 4.5 times longer than the baseline interval ( 16.8 days ) . Median progression-free survival was 59.5 ( 95 % CI 41.0 - 83.0 ) days . Twelve patients experienced adverse events considered related to aflibercept treatment including hypertension ( 7 patients ) , headache , anorexia , and dysphonia ( 3 patients each ) . Two patients experienced Grade 3/4 treatment-related adverse events ( Grade 3 hypertension and weight loss in one patient , Grade 3 intestinal perforation in one patient ) . CONCLUSION Aflibercept 4mg/kg every 2 weeks was effective at controlling malignant ascites , reducing the interval between repeat paracenteses . The safety profile was consistent with that reported for anti-VEGF agents OBJECTIVE Imatinib mesylate ( IM , Gleevec ) , a potent PDGF/PDGFR tyrosine kinase inhibitor , affects stroma and vascular endothelial cells . Our study sought to determine the safety and activity of paclitaxel with an intermittent schedule of IM . MATERIAL S AND METHODS rEOC patients previously treated with platinum/paclitaxel and ≤2 regimens for recurrence were enrolled . Paclitaxel 80 mg/m2 was given on days 3 , 10 , 17 every 28 days and oral IM 300 mg bid on days 1 - 4 , 8 - 11 , and 13 - 18 . RESULTS Between 2007 - 2009 , 14 patients enrolled , 12 were evaluable . Nine patients were on study at 12 weeks . Objective responses ( by RECIST and /or CA125 ) occurred in 4 patients . There were no grade 4 , and only four grade 3 toxic events : diarrhea , edema and 2 cases of neutropenia . Early study closure was due to sufficient safety information with preliminary encouraging efficacy results . CONCLUSION This weekly paclitaxel regimen with intermittent IM is tolerable with anti-tumor activity , making it suitable as part of future studies PURPOSE To estimate the efficacy and toxicity of AMG 386 , an investigational peptide-Fc fusion protein that neutralizes the interaction between the Tie2 receptor and angiopoietin-1/2 , plus weekly paclitaxel in patients with recurrent ovarian cancer . PATIENTS AND METHODS Patients with recurrent epithelial ovarian , fallopian tube , or primary peritoneal cancer were r and omly assigned 1:1:1 to receive paclitaxel ( 80 mg/m(2 ) once weekly [ QW ] , 3 weeks on/1 week off ) plus intravenous AMG 386 10 mg/kg QW ( arm A ) , AMG 386 3 mg/kg QW ( arm B ) , or placebo QW ( arm C ) . The primary end point was progression-free survival ( PFS ) . Secondary end points included overall survival , objective response , CA-125 response , safety , and pharmacokinetics . RESULTS One hundred sixty-one patients were r and omly assigned . Median PFS was 7.2 months ( 95 % CI , 5.3 to 8.1 months ) in arm A , 5.7 months ( 95 % CI , 4.6 to 8.0 months ) in arm B , and 4.6 months ( 95 % CI , 1.9 to 6.7 months ) in arm C. The hazard ratio for arms A and B combined versus arm C was 0.76 ( 95 % CI , 0.52 to 1.12 ; P = .165 ) . Further analyses suggested an exploratory dose-response effect for PFS across arms ( Tarone 's test , P = .037 ) . Objective response rates for arms A , B , and C were 37 % , 19 % , and 27 % , respectively . The incidence of grade ≥ 3 adverse events ( AEs ) in arms A , B , and C was 65 % , 55 % , and 64 % , respectively . Frequent AEs included hypertension ( 8 % , 6 % , and 5 % in arms A , B , and C , respectively ) , peripheral edema ( 71 % , 51 % , and 22 % in arms A , B , and C , respectively ) , and hypokalemia ( 21 % , 15 % , and 5 % in arms A , B , and C , respectively ) . AMG 386 exhibited linear pharmacokinetic properties at the tested doses . CONCLUSION AMG 386 combined with weekly paclitaxel was tolerable , with a manageable and distinct toxicity profile . The data suggest evidence of antitumor activity and a dose-response effect , warranting further studies in ovarian cancer BACKGROUND Paclitaxel and carboplatin given every 3 weeks is st and ard treatment for advanced ovarian carcinoma . Attempts to improve patient survival by including other drugs have yielded disappointing results . We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer . METHODS Patients with stage II to IV epithelial ovarian cancer , fallopian tube cancer , or primary peritoneal cancer were eligible for enrolment in this phase 3 , open-label , r and omised controlled trial at 85 centres in Japan . Patients were r and omly assigned by computer-generated r and omisation sequence to receive six cycles of either paclitaxel ( 180 mg/m(2 ) ; 3-h intravenous infusion ) plus carboplatin ( area under the curve [ AUC ] 6 mg/mL per min ) , given on day 1 of a 21-day cycle ( conventional regimen ; n=320 ) , or dose-dense paclitaxel ( 80 mg/m(2 ) ; 1-h intravenous infusion ) given on days 1 , 8 , and 15 plus carboplatin given on day 1 of a 21-day cycle ( dose-dense regimen ; n=317 ) . The primary endpoint was progression-free survival . Analysis was by intention to treat ( ITT ) . This trial is registered with Clinical Trials.gov , number NCT00226915 . FINDINGS 631 of the 637 enrolled patients were eligible for treatment and were included in the ITT population ( dose-dense regimen , n=312 ; conventional regimen , n=319 ) . Median progression-free survival was longer in the dose-dense treatment group ( 28.0 months , 95 % CI 22.3 - 35.4 ) than in the conventional treatment group ( 17.2 months , 15.7 - 21.1 ; hazard ratio [ HR ] 0.71 ; 95 % CI 0.58 - 0.88 ; p=0.0015 ) . Overall survival at 3 years was higher in the dose-dense regimen group ( 72.1 % ) than in the conventional treatment group ( 65.1 % ; HR 0.75 , 0.57 - 0.98 ; p=0.03 ) . 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early . Reasons for participant dropout were balanced between the groups , apart from withdrawal because of toxicity , which was higher in the dose-dense regimen group than in the conventional regimen group ( n=113 vs n=69 ) . The most common adverse event was neutropenia ( dose-dense regimen , 286 [ 92 % ] of 312 ; conventional regimen , 276 [ 88 % ] of 314 ) . The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group ( 214 [ 69 % ] ) than in the conventional treatment group ( 137 [ 44 % ] ; p<0.0001 ) . The frequencies of other toxic effects were similar between groups . INTERPRETATION Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer . FUNDING Bristol-Myers Squibb 5023 Background : GOG218 is a phase III r and omized , double-blind , placebo-controlled trial with three arms comparing both carboplatin and paclitaxel ( CP ) plus concurrent , or concurrent plus continued BEV ( CP+B-->B ) in stage III ( with macroscopic residual disease ) and stage IV EOC , PPC or FTC . Investigator assessment showed a clinical ly meaningful and statistically significant improvement in progression-free survival ( PFS ) for CP+B-->B when compared with CP therapy alone ( R.A. Burger , ASCO 2010 LBA1 ) . The PFS hazard ratios ( HR ) from the uncensored and censored ( censored for CA-125 and non- protocol therapy , INVc ) analyses were 0.72 ( p < 0.0001 ) and 0.644 ( p < 0.0001 ) , respectively . To determine the reliability of RECIST in assessing progression in ovarian cancer , an independent review of blinded radiologic and clinical data was conducted to confirm these results . METHODS Radiographic images and clinical data were provided to the independent review committee ( IRC ) . Data were review ed in a blinded fashion , in accordance with a pre-specified charter following RECIST criteria . PFS was analyzed as an intent-to-treat analysis of all r and omized subjects . RESULTS Images were su bmi tted for over 97 % of patients . High concordance between IRC and INVc was observed for progressive disease ( PD ) status ( 77 % ) and PD date ( 73 % ) . Further analysis of concordance and validation of other study endpoints is ongoing . CONCLUSIONS This is the largest IRC analysis ever conducted in patients with ovarian cancer , to our knowledge . The IRC and INVc PFS analyses were highly consistent , both confirming a significant increase in PFS for subjects treated with CP+B-->B versus CP alone . The size of the IRC , high participation rate , and strong concordance observed between IRC and INVc suggest that RECIST criteria can be applied objective ly in primary ovarian cancers . [ Table : see text ] PURPOSE Sunitinib is a multitargeted receptor tyrosine kinase inhibitor . We conducted a two-stage phase II study to evaluate the objective response rate of oral sunitinib in recurrent epithelial ovarian cancer . PATIENTS AND METHODS Eligibility required measurable disease and one or two prior chemotherapies , at least one platinum based . Platinum-sensitive or -resistant disease was allowed . Initial dose schedule was sunitinib 50 mg daily , 4 of 6 weeks . Observation of fluid accumulations during off-treatment periods result ed in adoption of continuous 37.5 mg daily dosing in the second stage of accrual . RESULTS Of 30 eligible patients , most had serous histology ( 67 % ) , were platinum sensitive ( 73 % ) and had two prior chemotherapies ( 60 % ) . One partial response ( 3.3 % ) and three CA125 responses ( 10 % ) were observed , all in platinum-sensitive patients using intermittent dosing . Sixteen ( 53 % ) had stable disease . Five had > 30 % decrease in measurable disease . Overall median progression-free survival was 4.1 months . Common adverse events included fatigue , gastrointestinal symptoms , h and -foot syndrome and hypertension . No gastrointestinal perforation occurred . CONCLUSIONS Single-agent sunitinib has modest activity in recurrent platinum-sensitive ovarian cancer , but only at the 50 mg intermittent dose schedule , suggesting that dose and schedule may be vital considerations in further evaluation of sunitinib in this cancer setting PURPOSE Angiogenesis is important for epithelial ovarian cancer ( EOC ) growth , and blocking angiogenesis can lead to EOC regression . Cediranib is an oral tyrosine kinase inhibitor ( TKI ) of vascular endothelial growth factor receptor ( VEGFR ) -1 , VEGFR-2 , VEGFR-3 , and c-kit . PATIENTS AND METHODS We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer ; cediranib was administered as a daily oral dose , and the original dose was 45 mg daily . Because of toxicities observed in the first 11 patients , the dose was lowered to 30 mg . Eligibility included < or= two lines of chemotherapy for recurrence . End points included response rate ( via Response Evaluation Criteria in Solid Tumors [ RECIST ] or modified Gynecological Cancer Intergroup CA-125 ) , toxicity , progression-free survival ( PFS ) , and overall survival ( OS ) . RESULTS Forty-seven patients were enrolled ; 46 were treated . Clinical benefit rate ( defined as complete response [ CR ] or partial response [ PR ] , stable disease [ SD ] > 16 weeks , or CA-125 nonprogression > 16 weeks ) , which was the primary end point , was 30 % ; eight patients ( 17 % ; 95 % CI , 7.6 % to 30.8 % ) had a PR , six patients ( 13 % ; 95 % CI , 4.8 % to 25.7 % ) had SD , and there were no CRs . Eleven patients ( 23 % ) were removed from study because of toxicities before two cycles . Grade 3 toxicities ( > 20 % of patients ) included hypertension ( 46 % ) , fatigue ( 24 % ) , and diarrhea ( 13 % ) . Grade 2 hypothyroidism occurred in 43 % of patients . Grade 4 toxicities included CNS hemorrhage ( n = 1 ) , hypertriglyceridemia/hypercholesterolemia/elevated lipase ( n = 1 ) , and dehydration/elevated creatinine ( n = 1 ) . No bowel perforations or fistulas occurred . Median PFS was 5.2 months , and median OS has not been reached ; median follow-up time is 10.7 months . CONCLUSION Cediranib has activity in recurrent EOC , tubal cancer , and peritoneal cancer with predictable toxicities observed with other TKIs OBJECTIVE Ovarian cancer is a highly angiogenic tumor and a model for antiangiogenic research . The tyrosine kinase receptor inhibitors target several receptors allowing for the pharmacological disruption of several independent pathways . Sunitinib malate is a multitargeted tyrosine kinase inhibitor . A phase II study utilizing a modified dosing schedule was conducted to assess the efficacy and safety of Sunitinib in recurrent ovarian , fallopian tube and peritoneal carcinoma . METHODS A nonr and omized phase II study was modeled as a two-stage Simon design initially enrolling 17 evaluable participants in stage one and 18 patients in stage two . Patients received the study drug at 37.5 mg every day over a 28 day treatment cycle until clinical or radiological evidence of progressive disease . Disease was evaluated radiographically and best overall response was defined using the RECIST 1.0 criteria . The primary objective of this study was to define the response rate ( defined as complete response and partial response ) while the secondary objectives included both the progression free rate as well as the safety of this agent in this patient population . RESULTS The response rate ( PR+CR ) was 8.3 % ( 95 % confidence interval : 1.8 % , 22.5 % ) . The 16-week and 24 week progression-free survival estimate was 36 % ( 95 % confidence interval and 19.2 % ) , respectively . The median progression-free survival estimate was 9.9 weeks . Hypertension and gastrointestional events were the most common toxicities noted . CONCLUSIONS A modest response rate of 8.3 % was achieved with Sunitinib malate . This phase II study adds to the body of literature of VEGFR inhibitors and further underscores the need of defining a genetic angiogenic signature LBA5002^ Background : In three phase III trials in OC ( 2 front line , 1 PT-sensitive recurrent ) , BEV + CT → BEV significantly improved progression-free survival ( PFS ) vs CT alone . AURELIA is the first r and omized trial of BEV in PT-resistant OC . METHODS Eligible patients ( pts ) had OC ( measurable by RECIST 1.0 or assessable ) that had progressed ≤6 mo after ≥4 cycles of PT-based therapy . Pts with refractory OC , history of bowel obstruction , or > 2 prior anticancer regimens were ineligible . After CT selection by the investigator ( pegylated liposomal doxorubicin [ PLD ] , topotecan [ TOP ] , or weekly paclitaxel [ PAC ] ) , pts were r and omized to CT either alone or with BEV ( 10 mg/kg q2w or 15 mg/kg q3w depending on CT ) until progression ( PD ) , unacceptable toxicity , or withdrawal of consent . Pts in the CT-alone arm could cross over to BEV monotherapy at PD . The primary endpoint was PFS by RECIST . Secondary endpoints included objective response rate ( ORR ) , overall survival , safety , and quality of life . The design provided 80 % power to detect a PFS hazard ratio ( HR ) of 0.7 with 2-sided log-rank test and α=0.05 after 247 events , assuming median PFS of 4.0 mo with CT and 5.7 mo with CT + BEV . RESULTS Between Oct 2009 and Apr 2011 , 361 pts were r and omized to receive selected CT ( PLD : 126 ; PAC : 115 ; TOP : 120 ) alone or with BEV . Median follow-up after 301 PFS events was 13.5 mo . CONCLUSIONS In PT-resistant OC , BEV + CT provides statistically significant and clinical ly meaningful improvement in PFS and ORR vs CT alone . Strict inclusion criteria minimized the incidence of BEV AEs . This is the first phase III trial in PT-resistant OC to show benefit with a targeted therapy and improved outcome with a combination vs monotherapy . [ Table : see text ] BACKGROUND Carboplatin plus paclitaxel administered every 3 weeks is st and ard first-line chemotherapy for patients with advanced ovarian cancer . A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial . The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks . METHODS We did a multicentre , r and omised , phase 3 study at 67 institutions in Italy and France . Women with FIGO stage IC-IV ovarian cancer , an ECOG performance status of 2 or lower , and who had never received chemotherapy were r and omly allocated in a 1:1 ratio to receive either carboplatin ( AUC 6 mg/mL per min ) plus paclitaxel ( 175 mg/m(2 ) ) every 3 weeks for six cycles or carboplatin ( AUC 2 mg/mL per min ) plus paclitaxel ( 60 mg/m(2 ) ) every week for 18 weeks . R and omisation was done by computer-based minimisation , stratified by centre , residual disease after surgery , and ECOG performance status . The study was not blinded . Co primary endpoints were progression-free survival and quality of life ( assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [ FACT-O/TOI ] score ) , and analysis was by modified intention to treat . This report presents the final analysis . The study is registered with Clinical Trials.gov , number NCT00660842 . FINDINGS 822 patients were enrolled into the study between Nov 20 , 2008 , and March 1 , 2012 ; 12 withdrew their consent immediately after r and omisation and were excluded , and 810 were eligible for analysis . 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule . After median follow-up of 22·3 months ( IQR 16·2 - 30·9 ) , 449 progression-free survival events were recorded . Median progression-free survival was 17·3 months ( 95 % CI 15·2 - 20·2 ) in patients assigned to treatment every 3 weeks , versus 18·3 months ( 16·8 - 20·9 ) in women allocated to the weekly schedule ( hazard ratio 0·96 , 95 % CI 0·80 - 1·16 ; p=0·66 ) . FACT-O/TOI scores differed significantly between the two schedules ( treatment-by-time interaction p<0·0001 ) ; with treatment every 3 weeks , FACT-O/TOI scores worsened at every cycle ( weeks 1 , 4 , and 7 ) , whereas for the weekly schedule , after transient worsening at week 1 , FACT-O/TOI scores remained stable . Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3 - 4 neutropenia ( 167 [ 42 % ] of 399 patients vs 200 [ 50 % ] of 400 patients ) , febrile neutropenia ( two [ 0·5 % ] vs 11 [ 3 % ] ) , grade 3 - 4 thrombocytopenia ( four [ 1 % ] vs 27 [ 7 % ] ) , and grade 2 or worse neuropathy ( 24 [ 6 % ] vs 68 [ 17 % ] ) . Three deaths during the study were attributed to chemotherapy ; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen . INTERPRETATION A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer . FUNDING None PURPOSE Sorafenib is a kinase inhibitor targeting Raf and other kinases ( ie , vascular endothelial growth factor receptor [ VEGFR ] , platelet-derived growth factor receptor [ PDGFR ] , Flt3 , and c-KIT ) . This study assessed its activity and tolerability in patients with recurrent ovarian cancer ( OC ) or primary peritoneal carcinomatosis ( PPC ) . METHODS This open-label , multi-institutional , phase II study used a two-stage design . Eligible patients had persistent or recurrent OC/PPC after one to two prior cytotoxic regimens , and they experienced progression within 12 months of platinum-based therapy . Treatment consisted of sorafenib 400 mg orally twice per day . Primary end points were progression-free survival ( PFS ) at 6 months and toxicity by National Cancer Institute criteria . Secondary end points were tumor response and duration of PFS and overall survival . Biomarker analyses included measurement of ERK and b-Raf expression in tumors and phosphorylation of ERK ( pERK ) in peripheral-blood lymphocytes ( PBLs ) before and after 1 month of treatment . Results Seventy-three patients were enrolled , of which 71 were eligible . Fifty-nine eligible patients ( 83 % ) had measurable disease , and 12 ( 17 % ) had detectable disease . Significant grade 3 or 4 toxicities included the following : rash ( n = 7 ) , h and -foot syndrome ( n = 9 ) , metabolic ( n = 10 ) , GI ( n = 3 ) , cardiovascular ( n = 2 ) , and pulmonary ( n = 2 ) . Only patients with measurable disease were used to assess efficacy . Fourteen survived progression free for at least 6 months ( 24 % ; 90 % CI , 15 % to 35 % ) . Two patients had partial responses ( 3.4 % ; 90 % CI , 1 % to 10 % ) ; 20 had stable disease ; 30 had progressive disease ; and seven could not have their tumor assessed . ERK and b-Raf were expressed in all tumors . Exploratory analyses indicated that pERK in post-treatment PBL specimens was associated with PFS . CONCLUSION Sorafenib has modest antitumor activity in patients with recurrent OC , but the activity was at the expense of substantial toxicity |
10,318 | 21,244,657 | The methods used to estimate these epidemiological parameters were highly variable in terms of the definition of COPD , severity scales , methods of investigation and target population s. Nevertheless , to a large extent , several recent international guidelines or research initiatives , such as GOLD , BOLD or PLATINO , have boosted a substantial st and ardization of methodology in data collection and have result ed in the availability of more comparable epidemiological estimates across countries .
On the basis of such st and ardization , severity estimates as well as prevalence estimates present much less variation across countries .
Conclusions The accuracy of COPD epidemiological parameters is important for guiding decision making with regard to preventive measures , interventions and patient management in various health care systems . | Background Chronic obstructive pulmonary disease ( COPD ) is predicted to become a major cause of death worldwide .
Studies on the variability in the estimates of key epidemiological parameters of COPD may contribute to better assessment of the burden of this disease and to helpful guidance for future research and public policies .
In the present study , we examined differences in the main epidemiological characteristics of COPD derived from studies across countries of the European Union , focusing on prevalence , severity , frequency of exacerbations and mortality , as well as on differences between the studies ' methods . | BACKGROUND Obstructive airways disease in older patients is reported to be not only common , but frequently overlooked and untreated by general practitioners . This study examines the value of screening elderly patients in a large semi-rural general practice for potentially treatable asthma and chronic obstructive pulmonary disease ( COPD ) . METHODS A r and om sample of 353 patients aged 60–75 years attended a nurse run screening clinic for pulmonary function testing , serial peak flow recording , and completion of a symptom question naire . Patients with a low forced expiratory volume in one second ( below the fifth centile of their predicted value ) or > 15 % mean diurnal variation in peak flow were referred to a doctor ’s clinic for further diagnostic assessment and /or to discuss possible treatment where appropriate . RESULTS Fifty eight patients ( 16.4 % ) had obstructive airways disease , the prevalence of asthma being 6.5 % and that of COPD 9.9 % . Of these , 30 had no previous diagnosis of airways disease and were not on treatment ; eight of them had significant airways reversibility and 10 were current smokers . No newly diagnosed patients had severe disease as measured by pulmonary function or quality of life assessment , and six patients accepted treatment . CONCLUSION Few older patients benefited from a screening programme for obstructive airways disease in a semi-rural general practice OBJECTIVES The prevalence of COPD in Greece is unknown . The aim of this study was to determine the prevalence and trends of COPD among adults in Greece . METHODS This study involved 888 r and omly identified adults ( 475 men and 413 women ) aged > 35 years , and smokers of at least 100 cigarettes , in a population -based , multiregional , cross-sectional descriptive design . The selected individuals reflected the urban/rural population distribution in Greece and , within each study region , the age group and gender of the community setting . The diagnosis of COPD was based on clinical and spirometric data including reversibility test ( DeltaFEV(1 ) < 15 % ) . RESULTS The overall prevalence of COPD in the population aged > 35 years with a smoking history of > 100 cigarettes per lifetime was 8.4 % . The gender-st and ardized COPD prevalence was 11.6 % for men and 4.8 % for women . The COPD prevalence by community setting was as follows : Athens , 6 % ; other urban areas , 10.1 % ; semiurban areas , 8.5 % ; and rural areas , 9.1 % . Smoking intensity and age were significantly associated with higher COPD prevalence in both men and women . CONCLUSIONS COPD is a substantial health problem in Greece , although prevalence rates are lower than expected when the high smoking rates are taken into account . The high proportion of the patients with mild COPD who were unaware of their illness highlights the need to increase public awareness of COPD BACKGROUND Previous studies showing that tiotropium improves multiple end points in patients with chronic obstructive pulmonary disease ( COPD ) led us to examine the long-term effects of tiotropium therapy . METHODS In this r and omized , double-blind trial , we compared 4 years of therapy with either tiotropium or placebo in patients with COPD who were permitted to use all respiratory medications except inhaled anticholinergic drugs . The patients were at least 40 years of age , with a forced expiratory volume in 1 second ( FEV(1 ) ) of 70 % or less after bronchodilation and a ratio of FEV(1 ) to forced vital capacity ( FVC ) of 70 % or less . Co primary end points were the rate of decline in the mean FEV(1 ) before and after bronchodilation beginning on day 30 . Secondary end points included measures of FVC , changes in response on St. George 's Respiratory Question naire ( SGRQ ) , exacerbations of COPD , and mortality . RESULTS Of a total of 5993 patients ( mean age , 65+/-8 years ) with a mean FEV(1 ) of 1.32+/-0.44 liters after bronchodilation ( 48 % of predicted value ) , we r and omly assigned 2987 to the tiotropium group and 3006 to the placebo group . Mean absolute improvements in FEV(1 ) in the tiotropium group were maintained throughout the trial ( ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation ) , as compared with the placebo group ( P<0.001 ) . After day 30 , the differences between the two groups in the rate of decline in the mean FEV(1 ) before and after bronchodilation were not significant . The mean absolute total score on the SGRQ was improved ( lower ) in the tiotropium group , as compared with the placebo group , at each time point throughout the 4-year period ( ranging from 2.3 to 3.3 units , P<0.001 ) . At 4 years and 30 days , tiotropium was associated with a reduction in the risks of exacerbations , related hospitalizations , and respiratory failure . CONCLUSIONS In patients with COPD , therapy with tiotropium was associated with improvements in lung function , quality of life , and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV(1 ) . ( Clinical Trials.gov number , NCT00144339 . Background The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease ( COPD ) are discussed controversially . Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent . We hypothesised that its known mucolytic , bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD . Methods In this double-blind , placebo-controlled multi-center- study we r and omly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time . The frequency , duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria . Secondary outcome measures included changes of lung function , respiratory symptoms and quality of life as well as the single parameters of the exacerbations . Results Baseline demographics , lung function and st and ard medication of both groups were comparable . During the treatment period of 6 months the multiple criteria frequency , severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo . Secondary outcome measures vali date d these findings . Improvement of lung function , dyspnea and quality of life as multiple criteria were statistically significant relative to placebo . Adverse events were comparable in both groups . Conclusion Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status . This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane . Trial registration IS RCT The present work aims to assess the international variation in the prevalence of chronic bronchitis and its main risk factor , smoking habits , in young adults of 35 centres from 16 countries . Respiratory symptoms and pulmonary function were assessed in 17,966 subjects ( 20 - 44 yrs ) , r and omly selected from the general population , in the frame of the European Community Respiratory Health Survey . The median prevalence of chronic bronchitis was 2.6 % , with wide variations across countries ( p<0.001 ; 0.7 - 9.7 % ) . The prevalence of current smokers ranged 20.1 - 56.9 % , ( p<0.001 ) with a median value of 40 % . Current smoking was the major risk factor for chronic bronchitis , especially in males . Its effect increased according to number of pack-yrs : in males , the odds ratio of chronic bronchitis was 3.51 ( 95 % confidence interval ( CI ) 2.31 - 5.32 ) in 1 - 14 pack-yrs smokers and increased to 17.32 ( 9.97 - 30.11 ) in > or = 45 pack-yrs smokers with respect to nonsmokers . Only 30 % of the geographical variability in prevalence could be explained by differences in smoking habits , suggesting that other environmental and /or genetic factors may play an important role . In conclusion , chronic bronchitis is a substantial health problem even in young adults . The impressive prevalence in current smokers in most countries highlights the need to improve the quality of prevention RATIONALE Exacerbations are key drivers of morbidity and mortality in chronic obstructive pulmonary disease ( COPD ) . OBJECTIVES We compared the relative efficacy of the long-acting inhaled bronchodilator/antiinflammatory combination ( salmeterol/fluticasone propionate ) 50/500 microg twice daily and the long-acting bronchodilator ( tiotropium ) 18 microg once daily in preventing exacerbations and related outcomes in severe and very severe COPD . METHODS A total of 1,323 patients ( mean age , 64 yr , post-bronchodilator FEV1 , 39 % predicted ) were r and omized in this 2-year , double-blind , double-dummy parallel study . MEASUREMENTS AND MAIN RESULTS Primary endpoint was health care utilization exacerbation rate . Other endpoints included health status measured by St. George 's Respiratory Question naire ( SGRQ ) , mortality , adverse events , and study withdrawal . Probability of withdrawing from the study was 29 % greater with tiotropium than salmeterol/fluticasone propionate ( P = 0.005 ) . The modeled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group ( rate ratio , 0.967 ; 95 % confidence interval [ CI ] , 0.836 - 1.119 ] ; P = 0.656 ) . The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionate versus tiotropium ( difference 2.1 units ; 95 % CI , 0.1 - 4.0 ; P = 0.038 ) . Mortality was significantly lower in the salmeterol/fluticasone propionate group ; 21 ( 3 % ) of patients in this group died compared with 38 ( 6 % ) in the tiotropium group ( P = 0.032 ) . More pneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium ( P = 0.008 ) . CONCLUSIONS We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium . More patients failed to complete the study while receiving tiotropium . A small statistically significant beneficial effect was found on health status , with an unexpected finding of lower deaths in salmeterol/fluticasone propionate-treated patients . Clinical trial registered with www . clinical trials.gov ( NCT 00361959 ) BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often present with severe acute exacerbations requiring hospital treatment . However , little is known about the prognostic consequences of these exacerbations . A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality . METHODS Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital ( visits to the emergency service and admissions ) , patient age , smoking , body mass index , co-morbidity , long term oxygen therapy , forced spirometric parameters , and arterial blood gas tensions in a prospect i ve cohort of 304 men with COPD followed up for 5 years . The mean ( SD ) age of the patients was 71 ( 9 ) years and forced expiratory volume in 1 second was 46 (17)% . RESULTS Only older age ( hazard ratio ( HR ) 5.28 , 95 % CI 1.75 to 15.93 ) , arterial carbon dioxide tension ( HR 1.07 , 95 % CI 1.02 to 1.12 ) , and acute exacerbations of COPD were found to be independent indicators of a poor prognosis . The patients with the greatest mortality risk were those with three or more acute COPD exacerbations ( HR 4.13 , 95 % CI 1.80 to 9.41 ) . CONCLUSIONS This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis . Mortality increases with the frequency of severe exacerbations , particularly if these require admission to hospital This r and omised , double-blind , parallel-group , 1-yr study compared the effect of tiotropium 18 microg once daily ( n=500 ) and placebo ( n=510 ) on exacerbations , associated health re source use ( HRU ) and airflow limitation in chronic obstructive pulmonary disease ( COPD ) patients . The mean+/-sd number of exacerbations during the past year was 2.14+/-1.40 , the mean weekly morning peak expiratory flow ( PEF ) was 259.6+/-96.1 L.min-1 and the mean forced expiratory volume in one second ( FEV1 ) was 1.37+/-0.45 L. Tiotropium significantly delayed the time to first exacerbation by approximately 100 days , reduced the proportion of patients experiencing more than one exacerbation by 17 % , and decreased the number of exacerbations by 35 % and exacerbation days by 37 % versus placebo . Tiotropium also decreased HRU versus placebo , as indicated by the significant reductions in the use of concomitant respiratory medications , antibiotics and oral steroids , and the number of unscheduled physician contacts . Mean weekly morning PEF improved significantly with tiotropium versus placebo from week 1 until the end of the study . At the end of the study , tiotropium significantly improved trough ( pre-dose ) FEV1 , forced vital capacity , slow vital capacity and inspiratory capacity versus placebo . In conclusion , tiotropium reduced exacerbations and associated health re source use , and improved airflow over 1 yr in chronic obstructive pulmonary disease patients Exacerbations of chronic obstructive pulmonary disease ( COPD ) are associated with worse health and increased healthcare utilisation . The Inhaled Steroids in Obstructive Lung Disease in Europe ( ISOLDE ) study in COPD showed a 26 % reduction in the yearly rate of exacerbations in patients treated with fluticasone propionate ( FP ) compared to placebo , but did not indicate which patients showed greatest benefit . In this study the patients were stratified into mild and moderate‐to‐severe COPD using the American Thoracic Society criterion of forced expiratory volume in one second ( FEV1 ) 50 % predicted , and the total number of exacerbations and those requiring treatment with oral corticosteroids were examined . There were 391 ( 195 FP ) patients with mild COPD and 359 ( 180 FP ) patients with moderate‐to‐severe disease . The exacerbation rate was highly skewed in mild disease , but more normally distributed in moderate‐to‐severe disease . FP reduced the overall exacerbation rate in moderate‐to‐severe disease ( FP median rate 1.47 yr−1 , placebo 1.75 yr−1 ) , but not in mild disease ( FP 0.67 yr−1 , placebo 0.92 yr−1 ) . FP use was associated with fewer patients with ≥1 exacerbation·yr−1 being treated with oral corticosteroids ( mild : FP 8 % , placebo 16 % ; moderate‐to‐severe : FP 17 % , placebo 30 % ) . Effects of fluticasone propionate on exacerbations were seen predominantly in patients with a postbronchodilator forced expiratory volume in one second < 50 % predicted . These data support recommendations in the Global Initiative for Chronic Obstructive Disease treatment guidelines that inhaled corticosteroids should be considered in patients with moderate‐to‐severe chronic obstructive pulmonary disease who experience recurrent exacerbations Background : Chronic obstructive pulmonary disease ( COPD ) is a chronic disease with a high prevalence and rapidly increasing incidence rates . The effect of self-treatment of COPD exacerbations on the severity of exacerbations during a 1-year period was examined and a cost-effectiveness analysis was performed . Methods : Patients were r and omly allocated to four 2-hour self-management sessions , with or without training in self-treatment of exacerbations . Patients in the self-treatment group received an action plan with the possibility to initiate a course of prednisolone ( with or without antibiotics ) . During follow-up , all participants kept a daily symptom diary . These provided the data to calculate the frequency of exacerbations , the number of exacerbation days and mean daily severity scores . Results : Data were analysed for 142 r and omised patients ( self-treatment : n = 70 ; control : n = 72 ) . The frequency of exacerbations was identical in both study groups ( mean ( SD ) 3.5 ( 2.7 ) ) . Patients in the self-treatment group reported fewer exacerbation days ( median 31 ( interquartile range ( IQR ) 8.9–67.5 ) in the self-treatment group vs 40 ( IQR 13.3–88.2 ) in the control group ; p = 0.064 ) ; the difference was significant in the group of patients with a high number of exacerbation days per year ( > 137 ( 90th percentile of the whole study population ) ; p = 0.028 ) . The mean severity score of an exacerbation day was equal in both groups . No between-group differences were found in health-related quality of life . Cost-effectiveness analyses showed that applying self-treatment saved € 154 per patient , with a trend towards a lower probability for hospital admissions ( 0.20/patient/year in the self-treatment group vs 0.33/patient/year in the control group ; p = 0.388 ) and a significant reduction of health care contacts ( 5.37/patient/year in the self-treatment group vs 6.51/patient/year in the control group ; p = 0.043 ) . Conclusion : Self-treatment of exacerbations incorporated in a self-management programme leads to fewer exacerbation days and lower costs Background : A trial of corticosteroids has been recommended for all patients with chronic obstructive pulmonary disease ( COPD ) , with the subsequent “ response ” determining the treatment selected . This approach assumes that patients can be reliably divided into responder and non-responder groups . We have assessed whether such a separation is statistically valid , which factors influence the change in forced expiratory volume in 1 second ( FEV1 ) after prednisolone , and whether the prednisolone response predicts 3 year changes in FEV1 , health status , or number of exacerbations during placebo or fluticasone propionate treatment . Methods : Oral prednisolone 0.6 mg/kg was given for 14 days to 524 patients with COPD before r and omised treatment for 3 years with fluticasone propionate or placebo . Factors relating to change in FEV1 after prednisolone were investigated using multiple regression . The response to prednisolone was entered into separate mixed effects models of decline in FEV1 and health status during the 3 years of the study . Results : The post-bronchodilator FEV1 increased by a mean 60 ml ( CI 46 to 74 ) after prednisolone with a wide unimodal distribution . Current smoking was the factor most strongly associated with the change in FEV1 after prednisolone , with an increase of 35 ml in current smokers and 74 ml in confirmed ex-smokers ( p<0.001 ) . There was no relationship between the change in FEV1 after prednisolone and the response to inhaled bronchodilators , baseline FEV1 , atopic status , age , or sex . The response to prednisolone , however expressed , was unrelated to the subsequent change in FEV1 over the following 3 years on either placebo or fluticasone propionate . Regression to the mean effects explained much of the apparent prednisolone response . The significant effect of treatment on decline in health status was not predicted by the prednisolone response . Conclusion : Patients with COPD can not be separated into discrete groups of corticosteroid responders and non-responders . Current smoking reduces the FEV1 response to prednisolone . Prednisolone testing is an unreliable predictor of the benefit from inhaled fluticasone propionate in individual patients AIMS To investigate the impact of definition on the incidence of chronic obstructive pulmonary disease ( COPD ) exacerbations in primary care . METHODS In a one-year prospect i ve , observational study , data from diary cards were used to determine the incidence of symptom- and healthcare-defined exacerbations . One hundred and twenty seven patients completed > or = 80 % of days in the diary card and were included in the analysis . RESULTS Incidence of COPD exacerbation varied according to definition . Mean yearly rates were 2.3 for symptom- and 2.8 for healthcare-defined exacerbations . Although patients with FEV(1 ) < 50 % had a higher mean yearly rate of healthcare-defined exacerbations than those with FEV(1 ) > or = 50 % ( 3.2 vs 2.3 ; p=0.003 ) , patients with less severe disease reported recurrent exacerbations . There was limited agreement between symptom- and healthcare-defined exacerbations . CONCLUSION Lung function does not appear to be a valid criterion for assigning COPD management directed at patients with recurrent exacerbation We examined the severity of airway obstruction and the occurrence of respiratory symptoms in a large , nationally representative population sample and in a subgroup of subjects with chronic bronchitis and /or emphysema to obtain information for developing national prevention and treatment strategies for these diseases . The study population comprised of 7217 r and omly selected subjects ( aged 30 years and older ) who participated in a comprehensive health examination survey . The ' cases ' were subjects diagnosed as having chronic bronchitis and /or emphysema . The survey methods comprised of question naires , interviews , physical measurements , including spirometry , and clinical examinations . In the whole study population , the age-adjusted prevalence of chronic bronchitis and /or emphysema was 22 % among men and 7 % among women , whilst clinical ly relevant airways obstruction ( FEV1/FVC% < or = 69 ) was present in 11 % of men and in 5 % of women . The occurrence of chronic cough and phlegm production was lowest among the ' cases ' with pronounced obstruction ( in 68 % of men with severe and in 60 % of women with moderate obstruction ) , whereas cold air-associated dyspnoea aggravation showed an inverse relationship , occurring most commonly in men ( 80 % ) with severe obstruction . Unexpectedly , half of the bronchitic women had never smoked . We conclude that the occurrence of certain bronchitic symptoms , such as chronic cough and phlegm production and cold air-associated dyspnoea aggravation , may to some degree indicate different stages of the disease . Smoking was not closely associated with airflow limitation in women here OBJECTIVES To ascertain the prevalence , diagnostic level , and treatment of COPD in Spain through a multicenter study comprising seven different geographic areas . DESIGN AND PARTICIPANTS This is an epidemiologic , multicenter , population -based study conducted in seven areas of Spain . A total of 4,035 men and women ( age range , 40 to 69 years ) who were r and omly selected from a target population of 236,412 subjects participated in the study . INTERVENTIONS Eligible subjects answered the European Commission for Steel and Coal question naire . Spirometry was performed , followed by a bronchodilator test when bronchial obstruction was present . RESULTS The prevalence of COPD was 9.1 % ( 95 % confidence interval [ CI ] , 8.1 to 10.2 % ) , 15 % in smokers ( 95 % CI , 12.8 to 17.1 % ) , 12.8 % in ex-smokers ( 95 % CI , 10.7 to 14.8 % ) , and 4.1 % in nonsmokers ( 95 % CI , 3.3 to 5.1 % ) . The prevalence in men was 14.3 % ( 95 % CI , 12.8 to 15 . 9 % ) and 3.9 % in women ( 95 % CI , 3.1 to 4.8 % ) . Marked differences were observed between sexes in smoking ; the percentage of nonsmokers was 23 % in men and 76.3 % in women ( p<0.0001 ) . The prevalence of COPD varied among the areas , ranging from 4.9 % ( 95 % CI , 3.2 to 7.0 % ) in the area of the lowest prevalence to 18 % ( 95 % CI , 14.8 to 21.2 % ) in the area of the highest . There was no previous diagnosis of COPD in 78.2 % of cases ( 284 of 363 ) . Only 49.3 % of patients with severe COPD , 11.8 % of patients with moderate COPD , and 10 % of patients with mild COPD were receiving some kind of treatment for COPD . Multivariate analysis showed that individuals had a higher probability of having received a previous diagnosis of COPD if they lived in urban areas , were of male gender , were > 60 years old , had higher educational levels , had > 15 pack-year smoking history , or had symptoms of chronic bronchitis . CONCLUSIONS COPD is a very frequent disease in Spain , and presents significant geographic variations and a very low level of previous diagnosis and treatment , even in the most advanced cases Background : There are little data available on the prevalence of chronic obstructive pulmonary disease ( COPD ) in the United Kingdom . The Northern Irel and Cost and Epidemiology of Chronic Obstructive Pulmonary Disease ( NICE COPD ) study is a two-stage survey to examine the prevalence of obstructive lung disease in a general population sample in the Greater Belfast area . Methods : In stage one 4000 subjects aged 40–69 years were selected at r and om from the general population . They were posted a short screening question naire concerning respiratory symptoms . Respondents were divided into ‚ symptomatic ’ and ‚ asymptomatic ’ groups according to their responses . In stage two , a sample of symptomatic and asymptomatic subjects completed a more intensive assessment that included a detailed question naire on medical history , spirometry , skin allergy testing and serial peak flow measurements . Spirometric criteria for airflow obstruction were FEV1/FVC ratio of < 70 % with FEV1 < 80 % predicted . Subjects were assigned diagnoses according to a pre-arranged protocol . Results : The survey was conducted from May 1999 to May 2001 . There was a 67 % response rate to the stage 1 screening question naire and 1330 responders were identified as being eligible to take part in stage 2 . In total , 722 subjects completed a detailed assessment ( 50.8 % Male , symptomatic , n = 326 ; asymptomatic , n = 396 ) . COPD was diagnosed in 12.3 % ( 8.8 , 15.8 ) of the symptomatic and 2.2 % ( 0.8 , 3.6 ) of the asymptomatic group . The estimated prevalence of obstructive lung disease in the total population age 40–69 years was 14.4 % : 6.3 % COPD ; 7.2 % asthma ; 0.9 % with indeterminate airflow obstruction . In men , the prevalence of COPD varied from 4.9 % in those aged 40–49 years to 12.3 % in those aged 60–69 years and in women , varied from 1.4 % in 40–49 years of age to 4.5 % in 60–69 years . Conclusion : The data suggest that COPD and asthma are common conditions in the general population and should inform future plans to address the burden of OBJECTIVES To identify variables associated with mortality in patients admitted to the hospital for acute exacerbation of COPD . DESIGN Prospect i ve cohort study . SETTING Acute-care hospital in Barcelona ( Spain ) . PATIENTS One hundred thirty-five consecutive patients hospitalized for acute exacerbation of COPD , between October 1996 and May 1997 . MEASUREMENTS AND RESULTS Clinical , spirometric , and gasometric variables were evaluated at the time of inclusion in the study . Socioeconomic characteristics , comorbidity , dyspnea , functional status , depression , and quality of life were analyzed . Mortality at 180 days , 1 year , and 2 years was 13.4 % , 22 % , and 35.6 % , respectively . Sixty-four patients ( 47.4 % ) were dead at the end of the study ( median follow-up duration , 838 days ) . Greater mortality was observed in the bivariate analysis among the oldest patients ( p < 0.0001 ) , women ( p < 0.01 ) , and unmarried patients ( p < 0.002 ) . Hospital admission during the previous year ( p < 0.001 ) , functional dependence ( Katz index ) [ p < 0.0004 ] , greater comorbidity ( Charlson index ) [ p < 0.0006 ] , depression ( Yesavage Scale ) [ p < 0.00001 ] ) , quality of life ( St. George 's Respiratory Question naire [ SGRQ ] ) [ p < 0.01 ] , and PCO(2 ) at discharge ( p < 0.03 ) were also among the significant predictors of mortality . In the multivariate analysis , the activity SGRQ subscale ( p < 0.001 ; odds ratio [ OR ] , 2.62 ; confidence interval [ CI ] , 1.43 to 4.78 ) , comorbidity ( p < 0.005 ; OR , 2.2 ; CI , 1.26 to 3.84 ) , depression ( p < 0.004 ; OR , 3.6 ; CI , 1.5 to 8.65 ) , hospital readmission ( p < 0.03 ; OR , 1.85 ; CI , 1.26 to 3.84 ) , and marital status ( p < 0.0002 ; OR , 3.12 ; CI , 1.73 to 5.63 ) were independent predictors of mortality . CONCLUSIONS Quality of life , marital status , depressive symptoms , comorbidity , and prior hospital admission provide relevant information of prognosis in this group of COPD patients Background The aim of this study was to analyse mortality and associated risk factors , with special emphasis on health status , medications and co-morbidity , in patients with chronic obstructive pulmonary disease ( COPD ) that had been hospitalized for acute exacerbation . Methods This prospect i ve study included 416 patients from each of the five Nordic countries that were followed for 24 months . The St. George 's Respiratory Question naire ( SGRQ ) was administered . Information on treatment and co-morbidity was obtained . Results During the follow-up 122 ( 29.3 % ) of the 416 patients died . Patients with diabetes had an increased mortality rate [ HR = 2.25 ( 1.28–3.95 ) ] . Other risk factors were advanced age , low FEV1 and lower health status . Patients treated with inhaled corticosteroids and /or long-acting beta-2-agonists had a lower risk of death than patients using neither of these types of treatment . Conclusion Mortality was high after COPD admission , with older age , decreased lung function , lower health status and diabetes the most important risk factors . Treatment with inhaled corticosteroids and long-acting bronchodilators may be associated with lower mortality in patients with COPD The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new , once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease ( COPD ) . This prospect i ve cost-effectiveness analysis was performed alongside two 1‐yr r and omised , double-blind clinical trials in the Netherl and s and Belgium . Patients had a diagnosis of COPD and a forced expiratory volume in one second ( FEV1 ) ≤65 % predicted normal . Patients were r and omised to tiotropium ( 18 µg once daily ) or ipratropium ( 2 puffs of 20 µg administered four times daily ) in a ratio of 2:1 . The mean number of exacerbations was reduced from 1.01 in the ipratropium group ( n=175 ) to 0.74 in the tiotropium group ( n=344 ) . The percentages of patients with a relevant improvement on the St. George 's Respiratory Question naire ( SGRQ ) were 34.6 % and 51.2 % respectively . Compared to ipratropium , the number of hospital admissions , hospital days and unscheduled visits to healthcare providers was reduced by 46 % , 42 % and 36 % respectively . Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 ( sem 160 ) in the tiotropium group and 1,541 ( SEM 163 ) in the ipratropium group ( difference 180 ) . Incremental cost-effectiveness ratios were 667 per exacerbation avoided and 1084 per patient with a relevant improvement on the SGRQ . Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 per patient per year BACKGROUND Inhaled long-acting beta2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease ( COPD ) , whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status . We postulated that a combination of these treatments would be better than each component used alone . METHODS 1465 patients with COPD were recruited from outpatient departments in 25 countries . They were treated in a r and omised , double-blind , parallel-group , placebo-controlled study with either 50 microg salmeterol twice daily ( n=372 ) , 500 microg fluticasone twice daily ( n=374 ) , 50 microg salmeterol and 500 microg fluticasone twice daily ( n=358 ) , or placebo ( n=361 ) for 12 months . The primary outcome was the pretreatment forced expiratory volume in 1s ( FEV1 ) after 12 months treatment ' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12h . Secondary outcomes were other lung function measurements , symptoms and rescue treatment use , the number of exacerbations , patient withdrawals , and disease-specific health status . We assessed adverse events , serum cortisol concentrations , skin bruising , and electrocardiograms . Analysis was as predefined in the study protocol . FINDINGS All active treatments improved lung function , symptoms , and health status and reduced use of rescue medication and frequency of exacerbations . Combination therapy improved pretreatment FEV1 significantly more than did placebo ( treatment difference 133 mL , 95 % CI 105 - 161 , p<0.0001 ) , salmeterol ( 73 mL , 46 - 101 , p<0.0001 ) , or fluticasone alone ( 95 mL , 67 - 122 , p<0.0001 ) . Combination treatment produced a clinical ly significant improvement in health status and the greatest reduction in daily symptoms . All treatments were well tolerated with no difference in the frequency of adverse events , bruising , or clinical ly significant falls in serum cortisol concentration . INTERPRETATION Because inhaled long-acting beta2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function , with no greater risk of side-effects than that with use of either component alone , this combination treatment should be considered for patients with COPD BACKGROUND : Chronic airways obstruction is common in adults and the elderly . To investigate the possibility that older adults with obstructive airways disease frequently do not receive appropriate treatment , the respiratory symptoms , medication use , and pulmonary function were studied in a r and om sample of white adults aged over 45 living in central Manchester , UK . METHODS : A postal question naire survey was performed on 783 men and women aged 45 years and over selected from GP lists by r and om number tables . Subjects completing the question naire were invited to attend for pulmonary function testing and methacholine challenge ( Newcastle dosimeter method ) . RESULTS : The question naire response rate was 92.3 % ( 723 subjects ) . The mean age of the population was 66.1 years and 57.2 % were women ; 29.2 % were current smokers and 37.3 % were ex-smokers . Asthma or bronchitis was reported by 30.0 % . Two hundred and forty seven representative subjects attended for pulmonary function testing and spirometric evidence of chronic airways obstruction was found in 26.4 % . Respiratory symptoms were reported by 76.6 % of subjects with chronic airways obstruction ; 55.0 % had features which may predict potential improvement on treatment ( increased non-specific bronchial responsiveness or significant bronchodilator reversibility ) . However , only 55.4 % of subjects with airways obstruction had received a diagnosis of asthma or chronic bronchitis and only 36.9 % were using inhaled bronchodilators or steroids . CONCLUSIONS : Chronic airways obstruction is very common in adults in this inner city population , but is frequently overlooked . Most subjects with chronic airways obstruction are not receiving appropriate treatment To perform a cross-sectional descriptive study of chronic obstructive pulmonary disease in the general population . We studied 600 men aged between 40 and 60 from a r and om sample ( 69.9 % of the total , 76.6 % eligible subjects ) . Each subject answered a question naire , underwent spirometric testing and measurement of CO in expired air . Smokers accounted for 50.8 % of the sample , although only 24.8 % of the population had CO levels in expired air greater than 10 ppm . The prevalence of chronic bronchitis was 9.2 % . Forty subjects ( 6.8 % ) , only 25 % of whom had previously undergone spirometry , met the criteria for air flow limitation . Air flow limitation was associated with chronic bronchitis and smoking , which were also mutually associated . Our data underline the need to combat smoking , given its relation with chronic bronchitis and airflow limitation , as well as to perform spirometry more routinely , mainly in smokers or patients with symptoms of chronic bronchitis OBJECTIVES COPD is increasingly recognized as a leading cause of global morbidity and mortality . Prevalence estimates for COPD are generally unavailable or unreliable . Thus , a simple and valid model for estimating COPD prevalence would provide essential information for policymakers in addressing a major burden of worldwide illness . METHODOLOGY We modelled the relationships among readily available demographic data ( e.g. age , gender ) , smoking prevalence , and COPD prevalence based on a literature review . We also included risks of COPD from environmental pollution and associations with socioeconomic status . RESULTS The model specifies a minimum of eight input variables to predict COPD prevalence in a given population : population by age , gender , smoking prevalence , prevalence of COPD among smokers , proportion living in rural areas , country by level of development , and exposures to environmental pollution . Actual COPD prevalence data from large population -based studies in Spain , Norway , Pol and and Nepal compared favourably with the model projections ( P > or = 0.10 ) . CONCLUSION The model is a simple tool for estimating the prevalence of COPD population s in a given region or country . Further studies are needed to prospect ively vali date the model and test the assumptions upon which it is based RATIONALE Frequent chronic obstructive pulmonary disease ( COPD ) exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation . Macrolides have airway antiinflammatory actions and may reduce the incidence of COPD exacerbations . OBJECTIVES To determine whether regular therapy with macrolides reduces exacerbation frequency . METHODS We performed a r and omized , double-blind , placebo-controlled study of erythromycin administered at 250 mg twice daily to patients with COPD over 12 months , with primary outcome variable being the number of moderate and /or severe exacerbations ( treated with systemic steroids , treated with antibiotics , or hospitalized ) . MEASUREMENTS AND MAIN RESULTS We r and omized 109 out patients : 69 ( 63 % ) males , 52 ( 48 % ) current smokers , mean ( SD ) age 67.2 ( 8.6 ) years , FEV1 1.32 ( 0.53 ) L , FEV1 % predicted 50 (18)% . Thirty-eight ( 35 % ) of the patients had three or more exacerbations in the year before recruitment , with no differences between treatment groups . There were a total of 206 moderate to severe exacerbations : 125 occurred in the placebo arm . Ten in the placebo group and nine in the macrolide group withdrew . Generalized linear modeling showed that the rate ratio for exacerbations for the macrolide-treated patients compared with placebo-treated patients was 0.648 ( 95 % confidence interval : 0.489 , 0.859 ; P = 0.003 ) and that these patients had shorter duration exacerbations compared with placebo . There were no differences between the macrolide and placebo arms in terms of stable FEV1 , sputum IL-6 , IL-8 , myeloperoxidase , bacterial flora , serum C-reactive protein , or serum IL-6 or in changes in these parameters from baseline to first exacerbation over the 1-year study period . CONCLUSIONS Macrolide therapy was associated with a significant reduction in exacerbations compared with placebo and may be useful in decreasing the excessive disease burden in this important patient population . Clinical trial registered with www . clinical trials.gov ( NCT 00147667 ) BACKGROUND A study was undertaken to record exacerbations and health re source use in patients with COPD during 6 months of treatment with tiotropium , salmeterol , or matching placebos . METHODS Patients with COPD were enrolled in two 6-month r and omised , placebo controlled , double blind , double dummy studies of tiotropium 18 micro g once daily via H and iHaler or salmeterol 50 micro g twice daily via a metered dose inhaler . The two trials were combined for analysis of heath outcomes consisting of exacerbations , health re source use , dyspnoea ( assessed by the transitional dyspnoea index , TDI ) , health related quality of life ( assessed by St George 's Respiratory Question naire , SGRQ ) , and spirometry . RESULTS 1207 patients participated in the study ( tiotropium 402 , salmeterol 405 , placebo 400 ) . Compared with placebo , tiotropium but not salmeterol was associated with a significant delay in the time to onset of the first exacerbation . Fewer COPD exacerbations/patient year occurred in the tiotropium group ( 1.07 ) than in the placebo group ( 1.49 , p<0.05 ) ; the salmeterol group ( 1.23 events/year ) did not differ from placebo . The tiotropium group had 0.10 hospital admissions per patient year for COPD exacerbations compared with 0.17 for salmeterol and 0.15 for placebo ( not statistically different ) . For all causes ( respiratory and non-respiratory ) tiotropium , but not salmeterol , was associated with fewer hospital admissions while both groups had fewer days in hospital than the placebo group . The number of days during which patients were unable to perform their usual daily activities was lowest in the tiotropium group ( tiotropium 8.3 ( 0.8 ) , salmeterol 11.1 ( 0.8 ) , placebo 10.9 ( 0.8 ) , p<0.05 ) . SGRQ total score improved by 4.2 ( 0.7 ) , 2.8 ( 0.7 ) and 1.5 ( 0.7 ) units during the 6 month trial for the tiotropium , salmeterol and placebo groups , respectively ( p<0.01 tiotropium v placebo ) . Compared with placebo , TDI focal score improved in both the tiotropium group ( 1.1 ( 0.3 ) units , p<0.001 ) and the salmeterol group ( 0.7 ( 0.3 ) units , p<0.05 ) . Evaluation of morning pre-dose FEV(1 ) , peak FEV(1 ) and mean FEV(1 ) ( 0 - 3 hours ) showed that tiotropium was superior to salmeterol while both active drugs were more effective than placebo . CONCLUSIONS Exacerbations of COPD and health re source usage were positively affected by daily treatment with tiotropium . With the exception of the number of hospital days associated with all causes , salmeterol twice daily result ed in no significant changes compared with placebo . Tiotropium also improved health related quality of life , dyspnoea , and lung function in patients with COPD BACKGROUND There is a lack of epidemiological data on COPD by disease severity . We have estimated the prevalence and underdiagnosis of COPD by disease severity defined by the British Thoracic Society ( BTS ) and Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) guidelines . The impact of smoking was evaluated by the population attributable fraction of smoking in COPD . METHODS A r and om sample of 1500 responders of the third postal survey performed in 1996 of the Obstructive Lung Disease in Northern Sweden ( OLIN ) Studies ' first cohort ( 6610 subjects recruited in 1985 ) were invited to structured interview and spirometry . One thous and two hundred and thirty-seven subjects ( 82 % ) performed spirometry . RESULTS The prevalence of mild BTS- COPD was 5.3 % , moderate 2.2 % , and severe 0.6 % ( GOLD- COPD : mild 8.2 % , moderate 5.3 % , severe 0.7 % , and very severe 0.1 % ) . All subjects with severe COPD were symptomatic , corresponding figures among mild COPD were 88 % and 70 % ( BTS and GOLD ) , Subjects with severe BTS- COPD reported a physician-diagnosis consistent with COPD in 50 % of cases , in mild BTS- COPD 19 % , while in mild GOLD- COPD only 5 % of cases . The major risk factors , age and smoking , had a synergistic effect on the COPD -prevalence . The Odds Ratio ( OR ) for having COPD among smokers aged 76 - 77 years was 59 and 34 ( BTS and GOLD ) when non-smokers aged 46 - 47 was used as reference population . CONCLUSIONS Most subjects with COPD have a mild disease . The underdiagnosis is related to disease-severity . Though being symptomatic , only a half of the subjects with severe COPD are properly labelled . Smoking and increasing age were the major risk factors and acted synergistic BACKGROUND COPD is a major cause of chronic morbidity and mortality throughout the world . Although the prevalence of COPD is already well documented , there are only few studies regarding the incidence of COPD . METHODS In a prospect i ve population -based cohort study among subjects aged > or= 55 years , COPD was diagnosed with an algorithm based on the validation of hospital discharge letters , files from the general practitioner , and spirometry reports . RESULTS In this study cohort of 7,983 participants , 648 cases were identified with incident COPD after a median follow-up time of 11 years ( interquartile range , 7.8 years ) . This result ed in an overall incidence rate ( IR ) of 9.2/1,000 person-years ( PY ) [ 95 % confidence interval ( CI ) , 8.5 to 10.0 ] . The IR of COPD was higher among men ( 14.4/1,000 PY ; 95 % CI , 13.0 to 16.0 ) than among women ( 6.2/1,000 PY ; 95 % CI , 5.5 to 7.0 ) , and higher in smokers than in never-smokers ( 12.8/1,000 PY ; 95 % CI , 11.7 to 13.9 and 3.9/1,000 PY ; 95 % CI , 3.2 to 4.7 , respectively ) . Remarkable was the high incidence in the youngest female age category of 55 to 59 years ( 7.4/1,000 PY ; 95 % CI , 4.1 to 12.6 ) . For a 55-year-old man and woman still free of COPD at cohort entry , the risk for the development of COPD over the coming 40 years was 24 % and 16 % , respectively . CONCLUSION The overall incidence of COPD in an elderly population is 9.2/1,000 PY , with a remarkably high incidence in the youngest women , suggesting a further shift toward the female sex in the gender distribution of COPD . During their further lives , one of four men and one of six women free of COPD at the age of 55 years will have COPD develop BACKGROUND Increased oxidative stress and bronchial inflammation are important mechanisms in the pathophysiology of COPD . AIM To investigate whether treatment with the inhaled corticosteroid fluticasone propionate ( FP ) or the anti-oxidative agent N-acetylcysteine ( NAC ) are effective in primary care patients . METHODS The study was a 3-year placebo-controlled r and omised controlled trial preceded by a 3-month washout and 2-week prednisolone pre-treatment . Patients were (ex-)smokers with chronic bronchitis or COPD . Interventions were inhaled FP 500microg b.i.d . , oral NAC 600 mg o.d . , or placebo . Exacerbation rate and quality of life measured with the Chronic Respiratory Question naire ( CRQ ) were the primary outcomes , FEV(1 ) decline and respiratory symptoms secondary outcomes . RESULTS 286 patients recruited from 44 general practice s were r and omised . Exacerbation rate was 1.35 times higher for NAC ( p=0.054 ) and 1.30 times higher for FP ( p=0.095 ) compared with placebo . CRQ total scores did not differ between NAC ( p=0.306 ) or FP ( p=0.581 ) treatment compared to placebo . Annual postbronchodilator FEV(1 ) decline was 64mL [ SD 5.4 ] for NAC [ p=0.569 versus placebo ] , 59mL [ SD 5.7 ] for FP [ p=0.935 ] , and 60mL [ SD 5.4 ] for placebo . CONCLUSION No beneficial treatment effects for either high-dosed inhaled fluticasone propionate or oral N-acetylcysteine were observed in our study population of patients with COPD or chronic bronchitis The prevalence of obstructive lung diseases is increasing in Sc and inavia and worldwide . The reasons for this are not known . The prevalence varies between countries but also between different areas within the same country . In northern Europe a north-south gradient and also an east-west gradient have been proposed . To our knowledge this is the first comprehensive epidemiological study concerning obstructive lung diseases and respiratory symptoms in the southern part of Sweden . The prevalence of bronchial asthma , chronic bronchitis/emphysema , respiratory symptoms , smoking habits and medication in a r and om sample of 12,071 adults aged 20 - 59 years was assessed in a postal survey with a slightly modified question naire previously used in central and northern Sweden ( the OLIN Studies ) . The question naire was based on the British Medical Research Council ( BMRC ) question naire . We also compared the prevalence figures of asthma found in the postal survey with those reported in the medical records in a part of the study area . After two reminders , the response rate was 70.1 % ( n = 8469 ) ; 33.8 % of the responders were smokers . Among younger ( 20 - 39 year age group ) individuals , smoking was most common in women , whereas in those aged 40 - 59 years , smoking was more common in men . In all , 469 subjects ( 5.5 % ) stated that they had asthma , 41.6 % of whom reported a family history of asthma compared to 15.9 % of the study sample not reporting asthma . Of all subjects reporting asthma , 60.1 % ( n = 282 ) answered that they used asthma drugs . Inhaled steroids were used by 20.7 % . Chronic bronchitis and /or emphysema was reported by 4.6 % ( n = 392 ) , 28.6 % of whom reported a family history of chronic bronchitis or emphysema compared to 6.8 % of the study sample not reporting chronic bronchitis . The most common respiratory symptom in the study population was ' phlegm when coughing ' reported by 15.1 % ( n = 1279 ) . Our data show a prevalence of self-reported asthma of 5.5 % compared with 7 % reported by Lunbäck et al. in northern Sweden , which indicates a north-south gradient OBJECTIVE To examine the prevalence of obstructive pulmonary diseases , respiratory symptoms , smoking habits and pulmonary medication in an adult population , and to compare the results with a study performed in the same geographical area in 1992 . DESIGN In 2000 , a postal question naire was sent to a r and omly selected population of 5179 subjects aged 20 - 59 years living in southern Sweden . RESULTS The participation rate was 71.3 % . Self-reported asthma was reported by 8.5 % of all respondents ( vs. 5.5 % in 1992 , P < 0.001 ) and 14.5 % of females aged 20 - 29 years . Self-reported chronic bronchitis and /or emphysema and /or chronic obstructive pulmonary disease ( CBE/ COPD ) was reported by 3.6 % ( vs. 4.6 % in 1992 , non-significant ) with the highest prevalence ( 5.7 % ) in the 50 - 59 year cohort . Smoking decreased from 33.3 % in 1992 to 28.4 % in 2000 ( P < 0.05 ) . About 46 % of asthmatics reported nocturnal respiratory symptoms , and 69 % reported having had asthma symptoms in the last 12 months . Use of inhaled steroids increased in subjects with asthma and CBE/ COPD from 19.4 % to 36.5 % ( P < 0.05 ) and from 8.6 % to 30.0 % ( P < 0.05 ) , respectively . CONCLUSIONS Self-reported asthma increased significantly between 1992 and 2000 , but the prevalence of CBE/ COPD was unchanged . The high proportion of reported symptoms in asthmatics despite an increased use of steroids suggests that further efforts are needed to improve asthma treatment BACKGROUND Remarkable overlap exists in symptoms between asthma and chronic obstructive pulmonary disease ( COPD ) , and the symptoms of the patients with mild asthma are often falsely thought to be caused by smoking . The objective of the study was to determine the prevalence of doctor-diagnosed asthma , asthmatic symptoms and doctor-diagnosed COPD in an adult population . The prevalence and relation to asthma of aspirin intolerance , nasal polyposis , allergic rhinitis and smoking habits were also examined . METHODS Postal question naire survey of a population -based r and om sample ( 4300 ) of adult women and men aged 18 - 65 years served by the Päijät-Häme Central Hospital in southern Finl and ( a region with 208 000 inhabitants ) was performed . RESULTS The non-response-adjusted prevalence ( Drane 's linear method ) of doctor-diagnosed asthma was 4.4 % ( 95 % CI : 3.3 - 5.5 % ) and of COPD 3.7 % ( 95 % CI : 2.7 - 4.8 % ) . The prevalence of allergic rhinitis was 37.3 % ( 95 % CI : 33.3 - 41.2 % ) , and of overall aspirin intolerance 5.7 % ( 95 % CI : 4.4 - 7.1 % ) . The observed prevalence of aspirin intolerance causing shortness of breath or attacks of asthma was 1.2 % and it was higher in patients with doctor-diagnosed asthma than without ( 8.8 % versus 0.8 % , relative risk [ RR ] = 11.4 , P < 0.0001 ) , and higher in those with allergic-like rhinitis than without ( 2.6 % versus 0.3 % , RR = 7.7 , P < 0.0001 ) . The prevalence of nasal polyposis was 4.3 % ( 95 % CI : 2.8 - 5.8 % ) . CONCLUSIONS The current prevalence of doctor-diagnosed asthma among adults is 4.4 % , and allergic rhinitis , nasal polyposis and aspirin intolerance are associated with an increased risk of asthma . There is also association between aspirin-induced asthma and allergic-like rhinitis BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is an important cause of morbidity and mortality worldwide . Diagnosis is customarily confirmed with spirometry , but there are few studies on documented spirometry use in everyday clinical practice . METHODS In a cross-sectional survey and study of the medical records of primary and secondary care COPD patients aged 18 - 75 in a Swedish region , patients with COPD were r and omly selected from the registers of 56 primary care centres and 14 hospital outpatient clinics . Spirometry data at diagnosis + /-6 months were analyzed . RESULTS From 1114 patients with COPD , 533 with a new diagnosis of COPD during the four-year study period were identified . In 59 % ( n=316 ) , spirometry data in connection with diagnosis were found in the medical records . Spirometry data with post-bronchodilator forced expiratory volume in 1s ( FEV(1))/ vital capacity ( VC ) ratios were available in 45 % ( n=241 ) . FEV1/VC ratio < 0.70 were found in 160 patients , which corresponds to 30 % of the patients with a new diagnosis . Lower age , female gender , current smoking , higher body mass index ( BMI ) and shorter forced exhalation time were related to COPD diagnosis despite an FEV(1)/VC ratio of > /=0.70 . The most common problem in the quality assessment was an insufficient exhalation time . CONCLUSIONS Only a third of Swedish patients with COPD had their diagnosis confirmed with spirometry . Our data indicate that female gender , current smoking , higher BMI and short exhalation time increase the risk of being diagnosed with COPD without fulfilling the spirometric criteria for the disease Four hundred sixty-seven patients between 35 and 65 years of age were studied , all taken from a r and om sample of the population of Health Area 5 of the Valencian Community . Figures for respiratory symptoms , smoking , previous lung disease , professional activity and lung function were obtained through question naires and spirometry . The prevalence of asthma found was 2.78 % ( C.I. 2.76 - 2.79 ) ; chronic bronchitis was 4.07 % ( C.I. 2.37 - 5.77 ) and airflow limitation was 6.4 % ( C.I. 4.5 - 8.3 ) . Smokers represented 33.2 % of the sample . A significant association was found between the level of intensity of symptoms and lung function . There were no differences between smokers and non smokers with respect to FEV1 % . An association between workplace exposure and spirometry was found only for FEV1/FVC% OBJECTIVE Chronic obstructive pulmonary disease ( COPD ) is a major health problem with high societal costs . The Global Initiative for Chronic Lung Disease ( GOLD ) has identified a need for health economics data for COPD . For chronic diseases , such as COPD , where the natural history of disease is lifetime , a modeling approach for economic evaluation may be more realistic than prospect i ve , piggy-backed clinical trials or specific COPD cohort studies . Simulation models can be used to extrapolate clinical data beyond the limited time frame of clinical trials , to analyze subgroups of patients or to explore uncertainty regarding the results by using sensitivity analysis techniques . Our purpose has been to develop a flexible computer simulation model for COPD that will represent disease progression and GOLD recommendations , useful for economic evaluations of new medicines to meet the needs of various payer requirements for reimbursement and re source allocation . METHODS This article describes a two-dimensional Markov model , which uses data from multiple sources about disease progression , exacerbation frequency and duration , mortality , costs , burden of illness , and the relationships between those variables . The model is evaluated using stochastic uncertainty analysis , it allows comparison of treatments affecting different disease mechanisms , and it uses primary data vali date d against published sources . RESULTS We have evaluated two hypothetical interventions treating different features of the disease ( lung function decline and acute exacerbations ) . These analyses show that reducing lung function decline must be a long-term strategy compared to reducing the number of exacerbations . It was necessary to have a long term like 30 years , with 10,000 patients and 20 % increase in price , or 20 years with equal prices to show cost-effectiveness with statistical significance for a treatment that reduces lung function decline . CONCLUSIONS Our study shows the value of modeling as a tool for evaluating different scenarios and for combining several sources of data , to provide estimates that would otherwise be unavailable . Clinical trials of this size and duration would be unrealistic BACKGROUND Acute exacerbations form a major component of the socioeconomic burden of COPD . As yet , little information is available about the long-term outcome of patients who have been hospitalized with acute exacerbations , although high mortality rates have been reported . STUDY OBJECTIVE The aim of this study was to investigate prospect ively the outcome for all patients admitted to the hospital with acute exacerbations of COPD during hospital admission and after 1-year of follow-up . Furthermore , patient characteristics related to increased mortality rate were analyzed . DESIGN We investigated prospect ively the 1-year mortality rate and potential determinants of mortality for all patients admitted to the hospital with an acute exacerbation between January 1 and December 31 , 1999 . RESULTS A total of 171 patients were included in the study . The mortality rate during hospital stay was 8 % , increasing to 23 % after 1 year of follow-up . Despite a comparable in-hospital mortality rate ( 6 % ) , the 1-year mortality rate was significantly higher for patients admitted to the ICU for respiratory failure ( 35 % ) . The multivariate Cox proportional hazards model was used to determine independent predictors of survival . Variables included in the regression model were age , sex , FEV(1 ) , PaO(2 ) , PaCO(2 ) , body mass index , long-term use of oral corticosteroids , comorbidity index , and hospital readmissions . The maintenance use of oral glucocorticosteroids ( relative risk [ RR ] , 5.07 ; 95 % confidence interval [ CI ] , 2.03 to 12.64 ) , PaCO(2 ) ( RR , 1.17 ; 95 % CI , 1.01 to 1.38 ) , and age ( RR , 1.07 ; 95 % CI , 1.01 to 1.12 ) were independently related to mortality . CONCLUSION We conclude that the prognosis for patients who have been admitted to the hospital for acute exacerbation of COPD is poor . Long-term use of oral corticosteroids , higher PaCO(2 ) , and older age could be identified as risk factors associated with higher mortality Abstract Objectives : To determine the effect of long term inhaled corticosteroids on lung function , exacerbations , and health status in patients with moderate to severe chronic obstructive pulmonary disease . Design : Double blind , placebo controlled study . Setting : Eighteen UK hospitals . Participants : 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second ( FEV1 ) 50 % of predicted normal . Interventions : Inhaled fluticasone propionate 500 μg twice daily from a metered dose inhaler or identical placebo . Main outcome measures : Efficacy measures : rate of decline in FEV1 after the bronchodilator and in health status , frequency of exacerbations , respiratory withdrawals . Safety measures : morning serum cortisol concentration , incidence of adverse events . Results : There was no significant difference in the annual rate of decline in FEV1 ( P=0.16 ) . Mean FEV1 after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo ( P<0.001 ) . Median exacerbation rate was reduced by 25 % from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate ( P=0.026 ) . Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate ( P=0.0043 ) . Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group ( 25 % v 19 % , P=0.034 ) . Conclusions : Fluticasone propionate 500 μg twice daily did not affect the rate of decline in FEV1 but did produce a small increase in FEV1 . Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status . These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease |
10,319 | 28,325,471 | There was very low QoE for other moderators or prognostic factors associated with MMF treatment outcomes . | OBJECTIVES We aim ed to summarize the evidence examining factors that predict differential response to mycophenolate mofetil ( MMF ) in systemic lupus erythematosus ( SLE ) . | The presence of renal noninflammatory necrotizing vasculopathy ( NNV ) is often associated with a severe form of lupus nephritis ( LN ) , which is unresponsive to st and ard therapy . We conducted a 6-month r and omized , prospect i ve , open-label trial comparing mycophenolate mofetil ( MMF ) ( 1.5—2.0 g/day ) with monthly i.v . cyclophosphamide ( CTX ) ( 0.75—1.0 g/m2 ) as induction therapy for class IV LN with NNV . The primary and second end points were complete remission ( CR ) and partial remission ( PR ) , respectively . Of 20 patients recruited , nine were r and omly assigned to MMF and 11 to CTX . The baseline characteristics between groups were not significant . CR was achieved in four patients ( 44.4 % ) receiving MMF and in none of the patients receiving CTX ( P = 0.026 ) . PR was achieved in two patients ( 22.2 % ) in the MMF group and three patients ( 27.2 % ) in the CTX group . The total remission rate ( CR + PR ) in the MMF and CTX group was 66.6 and 27.2 % , respectively ( P = 0.17 ) . MMF was more effective than i.v . CTX in reducing proteinuria and haematuria . Adverse events were significantly less frequent with MMF than with CTX ( P = 0.028 ) . MMF was superior to i.v . CTX in inducing CR of LN with NNV and had a more favourable safety profile . Lupus ( 2007 ) 16 , 707—712 Class V lupus nephritis ( LN ) occurs in one-fifth of biopsy-proven cases of systemic lupus erythematosus . To study the effectiveness of treatments in this group of patients , we pooled analysis of two large r and omized controlled multicenter trials of patients with diverse ethnic and racial background who had pure class V disease . These patients received mycophenolate mofetil ( MMF ) or intravenous cyclophosphamide ( IVC ) as induction therapy for 24 weeks , with percentage change in proteinuria and serum creatinine as end points . Weighted mean differences , pooled odds ratios , and confidence intervals were calculated by using a r and om-effects model . A total of 84 patients with class V disease were divided into equal groups , each group had comparable entry variables but one received MMF and one received IVC . Within these groups , 33 patients on MMF and 32 patients on IVC completed 24 weeks of treatment . There were no differences between the groups in mean values for the measured end points . Similarly , no difference was found regarding the number of patients who did not complete the study or who died . In patients with nephrotic syndrome , no difference was noted between those treated with MMF and IVC regarding partial remission or change in urine protein . Hence we found that the response to MMF as induction treatment of patients with class V LN appears to be no different from that to IVC BACKGROUND Although mycophenolate mofetil ( MMF ) is being increasingly used to manage lupus nephritis ( LN ) , long-term experience is limited . Despite treatment , a significant proportion of patients will be refractory to this regime . METHODS We report , in this observational study , our long-term experience treating 70 patients with biopsy-proven LN , with MMF as continuous induction-maintenance therapy , who were followed up prospect ively over a 5-year period . As rescue therapy for MMF-resistant cases , tacrolimus ( 0.075 mg/kg/day ) was added . The study primary end point was complete response ( CR ) . Secondary end points included partial response ( PR ) , treatment failure , relapse and side effects . Predictor factors associated to renal outcome were analysed by Cox regression analysis . RESULTS Thirty-six MMF-treated patients ( 51 % ) remained in CR , and 23 ( 33 % ) failed treatment at last follow-up . Time to treatment failure was associated with persistent hypoalbuminaemia ( hazard ratio ( HR ) = 0.87 ; 95%CI , 0.81 - 0.95 ; P = 0.001 ) , higher proteinuria ( HR = 1.29 ; 95%CI , 1.03 - 1.62 ; P = 0.030 ) and fewer early responses ( HR 0.28 ; 95%CI , 0.10 - 0.77 ; P = 0.014 ) . Renal relapse occurred in 24 ( 34 % ) patients . Time to flare was associated with persistent anti-dsDNA titres ( HR = 1.001 ; 95%CI , 1.001 - 1.003 ; P = 0.005 ) and younger age at inclusion ( HR = 0.36 ; 95%CI , 0.14 - 0.90 ; P = 0.029 ) . Tacrolimus was added to 17 ( 24 % ) patients . A significant reduction of proteinuria was already observed at 3 months ( P = 0.002 ) . After 2 years follow-up , 12 ( 70 % ) of them achieved clinical response ( six CR and six PR ) . Conclusions . MMF is an effective treatment for LN . Combination therapy with tacrolimus is an effective and safe alternative for MMF-resistant patients Background Current method ological guidelines provide advice about the assessment of sub-group analysis within RCTs , but do not specify explicit criteria for assessment . Our objective was to provide research ers with a set of criteria that will facilitate the grading of evidence for moderators , in systematic review s. Method We developed a set of criteria from method ological manuscripts ( n = 18 ) using snowballing technique , and electronic data base search es . Criteria were review ed by an international Delphi panel ( n = 21 ) , comprising authors who have published method ological papers in this area , and research ers who have been active in the study of sub-group analysis in RCTs . We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data . Free responses were coded for consensus and disagreement . In a subsequent round additional criteria were extracted from the Cochrane Review ers ' H and book , and the process was repeated . Results The recommendations are that meta-analysts report both confirmatory and exploratory findings for sub-groups analysis . Confirmatory findings must only come from studies in which a specific theory/ evidence based a-priori statement is made . Exploratory findings may be used to inform future/subsequent trials . However , for inclusion in the meta- analysis of moderators , the following additional criteria should be applied to each study : Baseline factors should be measured prior to r and omisation , measurement of baseline factors should be of adequate reliability and validity , and a specific test of the interaction between baseline factors and interventions must be presented . Conclusions There is consensus from a group of 21 international experts that method ological criteria to assess moderators within systematic review s of RCTs is both timely and necessary . The consensus from the experts result ed in five criteria divided into two groups when synthesis ing evidence : confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research . These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies Background Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis ( LN ) . This investigator-initiated r and omised trial tested whether mycophenolate mofetil ( MMF ) was superior to azathioprine ( AZA ) as maintenance treatment . Methods A total of 105 patients with lupus with proliferative LN were included . All received three daily intravenous pulses of 750 mg methylprednisolone , followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg . Based on r and omisation performed at baseline , AZA ( target dose : 2 mg/kg/day ) or MMF ( target dose : 2 g/day ) was given at week 12 . Analyses were by intent to treat . Time to renal flare was the primary end point . Mean ( SD ) follow-up of the intent-to-treat population was 48 ( 14 ) months . Results The baseline clinical , biological and pathological characteristics of patients allocated to AZA or MMF did not differ . Renal flares were observed in 13 ( 25 % ) AZA-treated and 10 ( 19 % ) MMF-treated patients . Time to renal flare , to severe systemic flare , to benign flare and to renal remission did not statistically differ . Over a 3-year period , 24 h proteinuria , serum creatinine , serum albumin , serum C3 , haemoglobin and global disease activity scores improved similarly in both groups . Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients . Adverse events did not differ between the groups except for haematological cytopenias , which were statistically more frequent in the AZA group ( p=0.03 ) but led only one patient to drop out . Conclusions Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance Recent studies have suggested that mycophenolate mofetil ( MMF ) may offer advantages over intravenous cyclophosphamide ( IVC ) for the treatment of lupus nephritis , but these therapies have not been compared in an international r and omized , controlled trial . Here , we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational , two-phase ( induction and maintenance ) study . We r and omly assigned 370 patients with classes III through V lupus nephritis to open-label MMF ( target dosage 3 g/d ) or IVC ( 0.5 to 1.0 g/m(2 ) in monthly pulses ) in a 24-wk induction study . Both groups received prednisone , tapered from a maximum starting dosage of 60 mg/d . The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine . Secondary end points included complete renal remission , systemic disease activity and damage , and safety . Overall , we did not detect a significantly different response rate between the two groups : 104 ( 56.2 % ) of 185 patients responded to MMF compared with 98 ( 53.0 % ) of 185 to IVC . Secondary end points were also similar between treatment groups . There were nine deaths in the MMF group and five in the IVC group . We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events , serious adverse events , or infections . Although most patients in both treatment groups experienced clinical improvement , the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis 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 In the United States , approximately 35 % of adults with Systemic Lupus Erythematosus ( SLE ) have clinical evidence of nephritis at the time of diagnosis ; with an estimated total of 50–60 % developing nephritis during the first 10 years of disease [ 1–4 ] . The prevalence of nephritis is significantly higher in African Americans and Hispanics than in Caucasians , and is higher in men than in women . Renal damage is more likely to develop in non-Caucasian groups [ 2–4 ] . Overall survival in patients with SLE is approximately 95 % at 5 years after diagnosis and 92 % at 10 years [ 5 , 6 ] . The presence of lupus nephritis significantly reduces survival , to approximately 88 % at 10 years , with even lower survival in African Americans [ 5 , 6 ] . The American College of Rheumatology ( ACR ) last published guidelines for management of systemic lupus erythematosus ( SLE ) in 1999 [ 7 ] . That publication was design ed primarily for education of primary care physicians and recommended therapeutic and management approaches for many manifestations of SLE . Recommendations for management of lupus nephritis ( LN ) consisted of pulse glucocorticoids followed by high dose daily glucocorticoids in addition to an immunosuppressive medication , with cyclophosphamide viewed as the most effective immunosuppressive medication for diffuse proliferative glomerulonephritis . Mycophenolate mofetil was not yet in use for lupus nephritis and was not mentioned . Since that time , many clinical trials of glucocorticoids-plus-immunosuppressive interventions have been published , some of which are high quality prospect i ve trials , and some not only prospect i ve but also r and omized . Thus , the ACR determined that a new set of management recommendations was in order . A combination of extensive literature review and the opinions of highly qualified experts , including rheumatologists , nephrologists and pathologists , has been used to reach the recommendations . The management strategies discussed here apply to lupus nephritis in adults , particularly to those receiving care in the United States of America , and include interventions that were available in the United States as of April 2011 . While these recommendations were developed using rigorous methodology , guidelines do have inherent limitations in informing individual patient care ; hence the selection of the term “ recommendations . ” While they should not supplant clinical judgment or limit clinical judgment , they do provide expert advice to the practicing physician managing patients with lupus nephritis OBJECTIVE To identify predictors of moderate-to-severe systemic lupus erythematosus ( SLE ) flare in 562 patients treated with st and ard therapy alone in phase III belimumab trials , and to evaluate the impact of st and ard therapies on preventing flares . METHODS Post hoc analysis assessed baseline demographics , disease activity , and biomarkers in patients with and those without flare at treatment weeks 24 and 52 . Severe flare was defined by the modified SLE Flare Index ( SFI ) and the development of any new British Isles Lupus Assessment Group ( BILAG ) A domain score . Severe and moderate flare was defined by development of 1 new BILAG A domain score or 2 new BILAG B domain scores . Baseline characteristics associated with a ≥10 % absolute difference or a ≥50 % increase in flare rates were considered predictive . RESULTS Frequencies of flares over 52 weeks according to the SFI , any new BILAG A domain score , and 1 new BILAG A domain score or 2 new BILAG B domain scores were 23.7 % , 23.1 % , and 32.0 % , respectively . Flare predictors by univariate analysis on all 3 indices at weeks 24 and 52 were a score ≥12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index ( SELENA-SLEDAI ) ; anti-double-str and ed DNA ( anti-dsDNA ) positivity ; proteinuria ( ≥0.5 gm/24 hours ) ; BILAG renal , vasculitic , and hematologic scores ; elevated C-reactive protein levels ; and B lymphocyte stimulator ( BLyS ) levels ≥2 ng/ml . Independent predictors by multivariate analysis at week 52 were SELENA-SLEDAI and /or BILAG renal involvement and anti-dsDNA ≥200 IU/ml ( on all 3 indices ) ; SELENA-SLEDAI and /or BILAG neurologic and vasculitic involvement ( on 2 indices : any new BILAG A domain score and 1 new BILAG A domain score or 2 new BILAG B domain scores ) ; BLyS levels ≥2 ng/ml ( on 2 indices : the SFI and 1 new BILAG A domain score or 2 new BILAG B domain scores ) ; and low C3 level ( on the SFI ) . Baseline medications did not significantly decrease or increase moderate-to-severe SLE flare risk . CONCLUSION Patients who were receiving st and ard SLE therapy and had renal , neurologic , or vasculitic involvement , elevated anti-dsDNA or BLyS levels , or low C3 had increased risk of clinical ly meaningful flare over 1 year . Hydroxychloroquine use was not predictive BACKGROUND Mycophenolate mofetil ( MMF ) frequently is used as an alternative to intravenous cyclophosphamide to treat lupus nephritis . Whether MMF is adequate for patients with severely decreased kidney function at the time of treatment is uncertain . STUDY DESIGN We conducted a post hoc subgroup analysis of patients with low estimated glomerular filtration rates ( eGFRs ) from a large trial of MMF compared to cyclophosphamide in lupus nephritis . SETTING S & PARTICIPANTS We included all patients with an eGFR < 30 mL/min/1.73 m(2 ) from the Aspreva Lupus Management Study ( ALMS ) . INTERVENTION MMF ( target , 3 g/d ) compared to monthly intravenous cyclophosphamide ( 0.5 - 1 g/m(2 ) ) . OUTCOMES We compared the proportion of patients that responded to therapy and change in eGFR over 24 weeks . MEASUREMENTS Response was evaluated by a decrease in proteinuria and stabilization or improvement of serum creatinine level . RESULTS Of 370 patients in ALMS , 32 were included in the subgroup analysis : 20 r and omly assigned to MMF and 12 r and omly assigned to cyclophosphamide treatment . The patients included were similar at baseline between groups . Four ( 20.0 % ) patients treated with MMF responded compared with 2 ( 16.7 % ) patients treated with cyclophosphamide ( risk ratio , 1.2 ; 95 % CI , 0.3 - 5.1 ; P = 0.9 ) . eGFR in the MMF group improved more quickly than in the cyclophosphamide group , by 1.51 ( 95 % CI , 0.99 - 2.02 ) mL/min/1.73 m(2 ) each week ( P < 0.001 ) . Serious adverse events occurred in 9 ( 45.0 % ) MMF-treated patients and 7 ( 63.6 % ) cyclophosphamide-treated patients ( P = 0.5 ) . LIMITATIONS Small sample size and post hoc subgroup of a larger trial . CONCLUSIONS We did not detect a difference in the primary outcome of response in patients with low eGFR treated with MMF or cyclophosphamide . However , MMF may result in quicker recovery of kidney function compared with those treated with cyclophosphamide . Larger studies including more patients with poor kidney function are warranted AIM This pilot study compared mycophenolate mofetil ( MMF ) and tacrolimus ( Tac ) in the treatment of severe membranous lupus nephritis ( MLN ) . METHOD This was a 24 month prospect i ve , r and omized , open-label multi-centre exploratory study on Chinese patients with biopsy-proven pure Class V MLN with nephrotic syndrome . Patients were r and omized to treatment with either MMF or Tac , both in combination with prednisolone and the efficacy and tolerability outcomes were examined . RESULTS Sixteen patients were included , seven in the MMF and nine in the Tac treatment arm . At 24 months the complete response , partial response and overall response rates were 57.1 % vs. 11.1 % ( P = 0.049 ) , 14.3 % vs. 44.4 % ( P = 0.197 ) and 71.4 % vs. 55.6 % ( P = 0.515 ) in the MMF and Tac groups , respectively . The two groups had similar reduction of proteinuria and longitudinal profiles of serum albumin and creatinine levels . Serum creatinine remained stable in both groups , except in two patients who had a transient increase associated with high Tac blood levels . Adverse events in the MMF group included herpes zoster in one patient and reversible leucopenia in another , while in the Tac group four patients had severe infections and one developed new onset diabetes . No relapse occurred during the study period . CONCLUSION Both MMF and Tac when combined with corticosteroids are effective treatment options for severe MLN 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 The safety and efficacy of mycophenolate mofetil ( MMF ) were evaluated in adolescent patients with systemic lupus erythematosus and active or active/chronic class III – V lupus nephritis . During the 24-week induction phase , patients were r and omized to oral MMF ( target dose 3.0 g/day ) or intravenous cyclophosphamide ( IVC ) ( 0.5–1.0 g/m2/month ) , plus prednisone . Response was defined as a decrease in 24-hour urine protein : creatinine ratio ( P : Cr ) to <3 in patients with baseline nephrotic range proteinuria , or by ≥50 % if subnephrotic baseline proteinuria , and stabilization ( ±25 % ) or improvement in serum creatinine . In the 36-month maintenance phase , induction therapy responders were r and omized 1:1 to MMF ( 1.0 g twice daily ) or oral azathioprine ( AZA ) ( 2 mg/kg/day ) , plus prednisone . In the induction phase , 10 patients received MMF and 14 received IVC ; 15 ( 62.5 % ) achieved treatment response ( MMF , 7 ( 70 % ) ; IVC , 8/15 ( 57.1 % ) ; p = 0.53 , odds ratio ( 95 % confidence interval ) 2.0 ( 0.2 , 15.5 ) ) . There was a non-statistically significant difference in maintenance of response to MMF ( 7/8 ; 87.5 % ) versus AZA ( 3/8 ; 37.5 % ) . Seven patients withdrew ( MMF , 2 ; AZA , 5 ) . During both phases , rates of serious adverse events were similar in both arms . During both phases treatment response with MMF was as effective as the comparator BACKGROUND Since anecdotal series and small , prospect i ve , controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis , larger trials are desirable . METHODS We conducted a 24-week r and omized , open-label , noninferiority trial comparing oral mycophenolate mofetil ( initial dose , 1000 mg per day , increased to 3000 mg per day ) with monthly intravenous cyclophosphamide ( 0.5 g per square meter of body-surface area , increased to 1.0 g per square meter ) as induction therapy for active lupus nephritis . A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response . The study protocol specified adjunctive care and the use and tapering of corticosteroids . The primary end point was complete remission at 24 weeks ( normalization of abnormal renal measurements and maintenance of baseline normal measurements ) . A secondary end point was partial remission at 24 weeks . RESULTS Of 140 patients recruited , 71 were r and omly assigned to receive mycophenolate mofetil and 69 were r and omly assigned to receive cyclophosphamide . At 12 weeks , 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses . In the intention-to-treat analysis , 16 of the 71 patients ( 22.5 percent ) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide ( 5.8 percent ) had complete remission , for an absolute difference of 16.7 percentage points ( 95 percent confidence interval , 5.6 to 27.9 percentage points ; P=0.005 ) , meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide . Partial remission occurred in 21 of the 71 patients ( 29.6 percent ) and 17 of the 69 patients ( 24.6 percent ) , respectively ( P=0.51 ) . Three patients assigned to cyclophosphamide died , two during protocol therapy . Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate . CONCLUSIONS In this 24-week trial , mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile Objective To compare the efficacy of tacrolimus ( TAC ) and mycophenolate mofetil ( MMF ) for the initial therapy of lupus nephritis ( LN ) . Study design This is an open r and omised controlled parallel group study . Methods Adult patients with biopsy-confirmed active LN ( class III/IV/V ) were r and omised to receive prednisolone ( 0.6 mg/kg/day for 6 weeks and tapered ) in combination with either TAC ( 0.06–0.1 mg/kg/day ) or MMF ( 2–3 g/day ) for 6 months . Good responders were shifted to azathioprine for maintenance . The primary outcome was the rate of complete renal response ( CR ) at 6 months and the secondary outcomes included partial renal response , renal flares and decline of renal function over time . Results 150 patients ( 92 % women ; aged 35.5±12.8 years ; 81 % class III/IV ) were r and omised ( 76 MMF , 74 TAC ) . At month 6 , the rate of CR was 59 % in the MMF and 62 % in the TAC group ( treatment difference : 3.0 % ( −12 % , 18 % ) ; p=0.71 ) . Major infective episodes occurred in 9.2 % patients treated with MMF and in 5.4 % patients treated with TAC ( p=0.53 ) . Maintenance therapy with azathioprine was given to 79 % patients . After 60.8±26 months , proteinuric and nephritic renal flares developed in 24 % and 18 % of patients in the MMF group and 35 % ( p=0.12 ) and 27 % ( p=0.21 ) in the TAC group , respectively . The cumulative incidence of a composite outcome of decline of creatinine clearance by ≥30 % , development of chronic kidney disease stage 4/5 or death was 21 % in the MMF and 22 % in the TAC group of patients ( p=0.35 ) . Conclusions TAC is non-inferior to MMF , when combined with prednisolone , for induction therapy of active LN . With azathioprine maintenance for 5 years , a non-significant trend of higher incidence of renal flares and renal function decline is observed with the TAC regimen . Trial registration number Hospital Authority Research Ethics Committee Clinical Trial Registry ( HARECCTR0500018 ; Hong Kong ) and US Clinical Trials.gov ( NCT00371319 ) Mycophenolic acid ( MPA ) , an effective immunosuppressive drug used in renal transplantation , is extensively glucuroni date d by several uridine diphosphate – glucuronosyltransferases ( UGTs ) into an inactive 7‐O‐glucuronide and , to a lesser extent , into a pharmacologically active acyl‐glucuronide . Experiments using human liver microsomes have shown that T—275A and C—2152 T single‐nucleotide polymorphisms ( SNPs ) of the UGT1A9 promoter region are associated with higher hepatic expression of UGT1A9 and increased in vitro glucuronidation activity for MPA WHAT IS KNOWN AND OBJECTIVE Mycophenolate mofetil ( MMF ) has been reported recently to be effective in the treatment of systemic lupus erythematosus ( SLE ) . The therapeutic range of mycophenolic acid ( MPA ) in SLE in the remission-maintenance phase remains to be clarified . The aim of this study was to evaluate the therapeutic efficacy of MMF and predose plasma concentrations of MPA and its phenolic glucuronide ( MPAG ) in patients with SLE in the remission-maintenance phase . METHODS Thirty-one patients with SLE receiving a fixed dosage regimen of MMF ( median and interquartile range , 1500 and 1000 - 2000mg/day ) for at least 1month and who had not experienced any adverse drug reactions for more than 3months were enrolled . RESULTS Significant improvement was observed after MMF administration in total haemolytic complement CH(50 ) and its fractions C3 and C4 , immunoglobulins IgG , IgA and IgM , anti-dsDNA antibody , serum concentration of albumin and red blood cell count , even though the mean daily dose of prednisolone was significantly reduced ( P=0·02 ) . Median predose plasma concentrations of MPA and MPAG were 1·95 and 26·2μg/mL ( interquartile ranges , 0·94 - 2·96 and 18·6 - 53·7 μg/mL ) . Predose plasma concentrations of MPA and MPAG correlated significantly with MMF dose ( r=0·64 , P<0·01 and r=0·39 , P=0·03 ) . WHAT IS NEW AND CONCLUSIONS MMF improved clinical laboratory markers and reduced prednisolone dosage in SLE patients with predose plasma concentration of MPA and MPAG in the interquartile ranges of 0·94 - 2·96 and 18·6 - 53·7μg/mL , respectively |
10,320 | 26,916,333 | The quality of the studies was high in relation to the clarity of aims , data collection and analysis , but weaker in terms of sample size and the use of theoretical frameworks . | Workplace stress is high among healthcare professionals ( HCPs ) and is associated with reduced psychological health , quality of care and patient satisfaction .
This systematic review and meta- analysis review s evidence on the effectiveness of mindfulness-based interventions ( MBIs ) for reducing stress in HCPs . | Purpose In addition to structural transformations , deeper changes are needed to enhance physicians ’ sense of meaning and satisfaction with their work and their ability to respond creatively to a dynamically changing practice environment . The purpose of this research was to underst and what aspects of a successful continuing education program in mindful communication contributed to physicians ’ well-being and the care they provide . Method In 2008 , the authors conducted in-depth , semistructured interviews with primary care physicians who had recently completed a 52-hour mindful communication program demonstrated to reduce psychological distress and burnout while improving empathy . Interviews with a r and om sample of 20 of the 46 physicians in the Rochester , New York , area who attended at least four of eight weekly sessions and four of eight monthly sessions were audio-recorded , transcribed , and analyzed qualitatively . The authors identified salient themes from the interviews . Results Participants reported three main themes : ( 1 ) sharing personal experiences from medical practice with colleagues reduced professional isolation , ( 2 ) mindfulness skills improved the participants ’ ability to be attentive and listen deeply to patients ’ concerns , respond to patients more effectively , and develop adaptive reserve , and ( 3 ) developing greater self-awareness was positive and transformative , yet participants struggled to give themselves permission to attend to their own personal growth . Conclusions Interventions to improve the quality of primary care practice and practitioner well-being should promote a sense of community , specific mindfulness skills , and permission and time devoted to personal growth UNLABELLED RATIONALE , AIMS & OBJECTIVE : Tools for the assessment of the quality of research studies tend to be specific to a particular research design ( e.g. r and omized controlled trials , or qualitative interviews ) . This makes it difficult to assess the quality of a body of research that addresses the same or a similar research question but using different approaches . The aim of this paper is to describe the development and preliminary evaluation of a quality assessment tool that can be applied to a method ologically diverse set of research articles . METHODS The 16-item quality assessment tool ( QATSDD ) was assessed to determine its reliability and validity when used by health services research ers in the disciplines of psychology , sociology and nursing . Qualitative feedback was also gathered from mixed- methods health research ers regarding the comprehension , content , perceived value and usability of the tool . RESULTS Reference to existing widely used quality assessment tools and experts in systematic review confirmed that the components of the tool represented the construct of ' good research technique ' being assessed . Face validity was subsequently established through feedback from a sample of nine health research ers . Inter-rater reliability was established through substantial agreement between three review ers when applying the tool to a set of three research papers ( κ = 71.5 % ) , and good to substantial agreement between their scores at time 1 and after a 6-week interval at time 2 confirmed test-retest reliability . CONCLUSIONS The QATSDD shows good reliability and validity for use in the quality assessment of a diversity of studies , and may be an extremely useful tool for review ers to st and ardize and increase the rigour of their assessment s in review s of the published papers which include qualitative and quantitative work Positive psychology has flourished in the last 5 years . The authors review recent developments in the field , including books , meetings , courses , and conferences . They also discuss the newly created classification of character strengths and virtues , a positive complement to the various editions of the Diagnostic and Statistical Manual of Mental Disorders ( e. g. , American Psychiatric Association , 1994 ) , and present some cross-cultural findings that suggest a surprising ubiquity of strengths and virtues . Finally , the authors focus on psychological interventions that increase individual happiness . In a 6-group , r and om-assignment , placebo-controlled Internet study , the authors tested 5 purported happiness interventions and 1 plausible control exercise . They found that 3 of the interventions lastingly increased happiness and decreased depressive symptoms . Positive interventions can supplement traditional interventions that relieve suffering and may someday be the practical legacy of positive psychology We investigated the impact of mindfulness training ( MT ) on working memory capacity ( WMC ) and affective experience . WMC is used in managing cognitive dem and s and regulating emotions . Yet , persistent and intensive dem and s , such as those experienced during high-stress intervals , may deplete WMC and lead to cognitive failures and emotional disturbances . We hypothesized that MT may mitigate these deleterious effects by bolstering WMC . We recruited 2 military cohorts during the high-stress predeployment interval and provided MT to 1 ( MT , n = 31 ) but not the other group ( military control group , MC , n = 17 ) . The MT group attended an 8-week MT course and logged the amount of out-of-class time spent practicing formal MT exercises . The operation span task was used to index WMC at 2 testing sessions before and after the MT course . Although WMC remained stable over time in civilians ( n = 12 ) , it de grade d in the MC group . In the MT group , WMC decreased over time in those with low MT practice time , but increased in those with high practice time . Higher MT practice time also corresponded to lower levels of negative affect and higher levels of positive affect ( indexed by the Positive and Negative Affect Schedule ) . The relationship between practice time and negative , but not positive , affect was mediated by WMC , indicating that MT-related improvements in WMC may support some but not all of MT 's salutary effects . Nonetheless , these findings suggest that sufficient MT practice may protect against functional impairments associated with high-stress context CONTEXT Primary care physicians report high levels of distress , which is linked to burnout , attrition , and poorer quality of care . Programs to reduce burnout before it results in impairment are rare ; data on these programs are scarce . OBJECTIVE To determine whether an intensive educational program in mindfulness , communication , and self-awareness is associated with improvement in primary care physicians ' well-being , psychological distress , burnout , and capacity for relating to patients . DESIGN , SETTING , AND PARTICIPANTS Before- and -after study of 70 primary care physicians in Rochester , New York , in a continuing medical education ( CME ) course in 2007 - 2008 . The course included mindfulness meditation , self-awareness exercises , narratives about meaningful clinical experiences , appreciative interviews , didactic material , and discussion . An 8-week intensive phase ( 2.5 h/wk , 7-hour retreat ) was followed by a 10-month maintenance phase ( 2.5 h/mo ) . MAIN OUTCOME MEASURES Mindfulness ( 2 subscales ) , burnout ( 3 subscales ) , empathy ( 3 subscales ) , psychosocial orientation , personality ( 5 factors ) , and mood ( 6 subscales ) measured at baseline and at 2 , 12 , and 15 months . RESULTS Over the course of the program and follow-up , participants demonstrated improvements in mindfulness ( raw score , 45.2 to 54.1 ; raw score change [ Delta ] , 8.9 ; 95 % confidence interval [ CI ] , 7.0 to 10.8 ) ; burnout ( emotional exhaustion , 26.8 to 20.0 ; Delta = -6.8 ; 95 % CI , -4.8 to -8.8 ; depersonalization , 8.4 to 5.9 ; Delta = -2.5 ; 95 % CI , -1.4 to -3.6 ; and personal accomplishment , 40.2 to 42.6 ; Delta = 2.4 ; 95 % CI , 1.2 to 3.6 ) ; empathy ( 116.6 to 121.2 ; Delta = 4.6 ; 95 % CI , 2.2 to 7.0 ) ; physician belief scale ( 76.7 to 72.6 ; Delta = -4.1 ; 95 % CI , -1.8 to -6.4 ) ; total mood disturbance ( 33.2 to 16.1 ; Delta = -17.1 ; 95 % CI , -11 to -23.2 ) , and personality ( conscientiousness , 6.5 to 6.8 ; Delta = 0.3 ; 95 % CI , 0.1 to 5 and emotional stability , 6.1 to 6.6 ; Delta = 0.5 ; 95 % CI , 0.3 to 0.7 ) . Improvements in mindfulness were correlated with improvements in total mood disturbance ( r = -0.39 , P < .001 ) , perspective taking subscale of physician empathy ( r = 0.31 , P < .001 ) , burnout ( emotional exhaustion and personal accomplishment subscales , r = -0.32 and 0.33 , respectively ; P < .001 ) , and personality factors ( conscientiousness and emotional stability , r = 0.29 and 0.25 , respectively ; P < .001 ) . CONCLUSIONS Participation in a mindful communication program was associated with short-term and sustained improvements in well-being and attitudes associated with patient-centered care . Because before- and -after design s limit inferences about intervention effects , these findings warrant r and omized trials involving a variety of practicing physicians Mindfulness-based stress reduction ( MBSR ) has produced behavioral , psychological , and physiological benefits , but these programs typically require a substantial time commitment from the participants . This study assessed the effects of a shortened ( low-dose [ ld ] ) work-site MBSR intervention ( MBSR-ld ) on indicators of stress in healthy working adults to determine if results similar to those obtained in traditional MBSR could be demonstrated . Participants were r and omized into MBSR-ld and wait-list control groups . Self-reported perceived stress , sleep quality , and mindfulness were measured at the beginning and end of the 6-week intervention . Salivary cortisol was assessed weekly . Significant reductions in perceived stress ( p = .0025 ) and increases in mindfulness ( p = .0149 ) were obtained for only the MBSR-ld group ( n = 22 ) . Scores on the global measure of sleep improved for the MBSR-ld group ( p = .0018 ) as well as for the control group ( p = .0072 ; n = 20 ) . Implication s and future research are discussed This article is the second in a series reporting on research exploring the effects of Mindfulness-based Stress Reduction on nurses and describes the quantitative data . The third article describes qualitative data . Treatment group participants reduced scores on 2 of 3 subscales of the Maslach Burnout Inventory significantly more than wait-list controls ; within-group comparisons for both groups pretreatment and posttreatment revealed similar findings . Changes were maintained as long as 3-month posttreatment . Implication s of these findings are discussed Cultivating Awareness and Resilience in Education ( CARE for Teachers ) is a mindfulness-based professional development program design ed to reduce stress and improve teachers ' performance and classroom learning environments . A r and omized controlled trial examined program efficacy and acceptability among a sample of 50 teachers r and omly assigned to CARE or waitlist control condition . Participants completed a battery of self-report measures at pre- and postintervention to assess the impact of the CARE program on general well-being , efficacy , burnout/time pressure , and mindfulness . Participants in the CARE group completed an evaluation of the program after completing the intervention . ANCOVAs were computed between the CARE group and control group for each outcome , and the pretest scores served as a covariate . Participation in the CARE program result ed in significant improvements in teacher well-being , efficacy , burnout/time-related stress , and mindfulness compared with controls . Evaluation data showed that teachers viewed CARE as a feasible , acceptable , and effective method for reducing stress and improving performance . Results suggest that the CARE program has promise to support teachers working in challenging setting s and consequently improve classroom environments This study implemented an innovative new model of delivering a Mindfulness-Based Stress Reduction ( MBSR ) program that replaces six of the eight traditional in-person sessions with group telephonic sessions ( tMBSR ) and measured the program 's impact on the health and well-being of nurses employed within a large health care organization . As part of a nonr and omized pre – post intervention study , 36 nurses completed measures of health , stress , burnout , self-compassion , serenity , and empathy at three points in time . Between baseline ( Time 1 ) and the end of the 8-week tMBSR intervention ( Time 2 ) , participants showed improvement in general health , t(37 ) = 2.8 , p < .01 , decreased stress , t(37 ) = 6.8 , p < .001 , decreased work burnout , t(37 ) = 4.0 , p < .001 , and improvement in several other areas . Improvements were sustained 4 months later ( Time 3 ) , and individuals who continued their MBSR practice after the program demonstrated better outcomes than those that did not . Findings suggest that the tMBSR program can be a low cost , feasible , and scalable intervention that shows positive impact on health and well-being , and could allow MBSR to be delivered to employees who are otherwise unable to access traditional , on-site programs Evidence -based medicine is crucial to contemporary healthcare . It is dependent on systematic review methodology modelled on an arguably inadequate hierarchy of evidence . There has been a significant increase in medical and health research using qualitative and mixed method design s. The perspective taken in this article is that we need to broaden our evidence base if we are to fully take account of issues of context , acceptability and feasibility in the development and implementation of healthcare interventions . One way of doing this is to use a range of methods that better fit the different aspects of intervention development and implementation . Methods for the systematic review of evidence , other than r and omised-controlled trials , are available and there is a readiness to incorporate these other types of evidence into good- practice guidance , but we need a clear methodology to translate these advances in research into the world of policy Abstract Health workers in general , and midwives and nurses in particular , experience high levels of stress/distress due to the nature of their work and workplaces ; and , their socialization into ways of working that minimizes the likelihood of self-care . Increasing interest in the development of resilient workers has meant an enormous growth in interest in the role of holistic practice s such as mindfulness meditation . Kabat-Zinn ’s mindfulness-based stress reduction ( MBSR ) is one of the most commonly used by those seeking to practise , theorize or research mindfulness across multiple context s. The primary aim of this study was to pilot the effectiveness of an adapted mindfulness-based stress reduction intervention on the psychological wellbeing of nurses and midwives . More specifically , we sought to test the acceptability and feasibility of a modified MBSR intervention to inform a future r and omized controlled trial ( RCT ) . The pilot study used a pre and post intervention design . Twenty midwives and 20 nurses participated in a one-day workshop , undertook to meditate daily for 8 weeks and completed pre and post intervention measures : general health question naire ( GHQ-12 ) ; sense of coherence ( SOC ) – orientation to life and the depression , anxiety and stress scale ( DASS ) . A subgroup took part in interviews or focus group discussion s of their experiences of the program and their ongoing mindfulness practice . The quantitative findings included significant improvements on the GHQ-12 , SOC and the stress subscale of the DASS . Qualitative findings support the acceptability of the intervention , and highlighted a number of issues related to feasibility of any future RCT . In conclusion , mindfulness practice holds promise for increasing individual and workplace resilience , however , meaningful research evidence from carefully constructed studies will be required to engage and motivate participation and organizational support |
10,321 | 29,076,263 | Compared with usual psychiatric care , family intervention was more effective in reducing care burden over all follow-up periods .
Family intervention was also superior to usual care with regards to caregiving experience in the short term and improved utilization of formal support and family functioning over longer-term follow up .
Mutual support is more effective than psychoeducation in improving family functioning when measured 1 to 2 years after the intervention but had equivalent effects on utilization of formal support services .
CONCLUSIONS This review provides evidence that family intervention is effective for caregivers of recent-onset psychosis , especially for care burden where the positive effects are enhanced over time | AIM We aim ed to systematic ally review the evidence of the effectiveness of family interventions for caregivers of people with recent-onset psychosis compared with usual psychiatric care .
A secondary objective was to directly compare the effects of different types of family interventions . | Schizophrenia is a disruptive and distressing illness , not only for the person affected but also for family members . Family intervention , particularly in a group format using a diverse range of modalities , is thought to effectively satisfy the informational needs of families and enhance their coping abilities when caring for a relative with schizophrenia , and thus reduce a patient ’s relapse from illness . This study tested the hypothesis that participants in a family psychoeducation and mutual support group would demonstrate significant improvements in levels of patient and family functioning and shorter duration of re-hospitalization than families in routine care . A r and omized controlled trial was conducted with a sample of 68 Chinese families of schizophrenia sufferers in Hong Kong , who were r and omly assigned to either a family psychoeducation and support group ( n = 34 ) , or a routine care group ( n = 34 ) . The interventions were delivered at two psychiatric outpatient clinics over a nine-month period . Results of multivariate analyses of variance test indicated that the psychoeducation and support group reported greater improvements on family and patient functioning and shorter lengths of patient hospitalizations at the two post-tests ( one month and one year after completion of the intervention ) , compared with the routine care group . The findings substantiate that within a Chinese context , psychoeducation and mutual support group intervention can effectively help families care for a mentally ill relative OBJECTIVE The present study aims to assess the efficacy of a structured psychoeducational group intervention for adolescents with early-onset psychosis and their families . The intervention was implemented in parallel in 2 separate groups by focusing specifically on problem-solving strategies and structured psychosis-related information to manage daily life difficulties associated with the disease , to mitigate crises , and to prevent relapses . METHOD We performed a 9-month , r and omized , rater-blinded clinical trial involving 55 adolescent patients with early-onset psychosis and either or both of their parents . A psychoeducational problem-solving group intervention ( n = 27 ) was compared with a nonstructured group intervention ( n = 28 ) . The primary outcomes were number of hospitalizations , days of hospitalization , and visits to the emergency department . The secondary outcome measures were clinical variables and family environment . RESULTS Assessment s were performed before and after the intervention . At the end of the group intervention , 15 % of patients in the psychoeducational group and 39 % patients in the nonstructured group had visited the emergency department ( χ² = 3.62 , df = 1 , p = .039 ) . The improvement in negative symptoms was more pronounced in the psychoeducational group ( 12.84 [ 7.87 ] ) than in the nonstructured group ( 15.81 [ 6.37 ] ) ( p = .039 ) . CONCLUSION A parallel psychoeducational group intervention providing written instructions in a structured manner could help adolescents with early-onset psychosis and their parents to manage crises by implementing problem-solving strategies within the family , thus reducing the number of visits to the emergency department . Negative symptoms improved in adolescents in the psychoeducational group . Clinical trial registration information -- Intervention Module AGES ( AGES-CM ) ; http:// clinical trials.gov/ ; NCT02101372 . [ corrected ] BACKGROUND Family intervention reduces relapse rates in psychosis . Cognitive-behavioural therapy ( CBT ) improves positive symptoms but effects on relapse rates are not established . AIMS To test the effectiveness of CBT and family intervention in reducing relapse , and in improving symptoms and functioning in patients who had recently relapsed with non-affective psychosis . METHOD A multicentre r and omised controlled trial ( IS RCT N83557988 ) with two pathways : those without carers were allocated to treatment as usual or CBT plus treatment as usual , those with carers to treatment as usual , CBT plus treatment as usual or family intervention plus treatment as usual . The CBT and family intervention were focused on relapse prevention for 20 sessions over 9 months . RESULTS A total of 301 patients and 83 carers participated . Primary outcome data were available on 96 % of the total sample . The CBT and family intervention had no effects on rates of remission and relapse or on days in hospital at 12 or 24 months . For secondary outcomes , CBT showed a beneficial effect on depression at 24 months and there were no effects for family intervention . In people with carers , CBT significantly improved delusional distress and social functioning . Therapy did not change key psychological processes . CONCLUSIONS Generic CBT for psychosis is not indicated for routine relapse prevention in people recovering from a recent relapse of psychosis and should currently be reserved for those with distressing medication-unresponsive positive symptoms . Any CBT targeted at this acute population requires development . The lack of effect of family intervention on relapse may be attributable to the low overall relapse rate in those with carers BACKGROUND Family intervention in schizophrenia can reduce patient relapse and improve medication adherence , but few studies on this have involved a Chinese population . AIMS To examine the effects of a mutual support group for Chinese families of people with schizophrenia , compared with psychoeducation and st and ard care . METHOD R and omised controlled trial in Hong Kong with 96 families of out- patients with schizophrenia , of whom 32 received mutual support , 33 psychoeducation and 31 st and ard care . The psychoeducation group included patients in all the sessions , the mutual support group did not . Intervention was provided over 6 months , and patient- and family-related psychosocial outcomes were compared over an 18-month follow-up . RESULTS Mutual support consistently produced greater improvement in patient and family functioning and caregiver burden over the intervention and follow-up periods , compared with the other two conditions . The number of readmissions did not decrease significantly , but their duration did . CONCLUSIONS Mutual support for families of Chinese people with schizophrenia can substantially benefit family and patient functioning and caregiver burden Background Caring for a young person experiencing first-episode psychosis is challenging and can affect carers ’ well-being adversely . While some face-to-face approaches have achieved promising outcomes , they are costly and re source -intensive to provide , restricting their reach and penetration . Guided self-help in book-form ( or bibliotherapy ) is an alternative but untested approach in these circumstances . In this study , we aim ed to evaluate carers ’ beliefs about the usefulness of problem-solving guided self-help manual for primary carers of young people with first-episode psychosis . Methods A qualitative process evaluation nested in a r and omised controlled trial , conducted across two early intervention psychosis services in Melbourne , Australia . 124 carers were r and omised to problem-solving guided self-help intervention or treatment as usual . We also undertook a qualitative process evaluation , using individual interviews , with a r and om sample of 24 of the intervention group . A thematic analysis of the qualitative data was undertaken , which is the subject of this paper . Interviews were conducted between January 2009 and September 2010 . Results Three themes were abstract ed from the data , reflecting carers ’ beliefs about the usefulness of the manual : promoting carers ’ well-being , increasing carers ’ underst and ing of and support for the young person with first-episode psychosis , and accessibility and delivery modes of the programme . Conclusion This process evaluation highlights that guided self-help is useful in informing and supporting carers of affected young people . While there is scope for broadening the delivery modes , the approach is easy to use and accessible , and can be used as a cost-effective adjunct to st and ard support provided to carers , by community mental health nurses and other clinicians . Trial registration Abstract Aim Caring for young people with first‐episode psychosis is difficult and dem and ing , and has detrimental effects on carers ' well‐being , with few evidence ‐based re sources available to assist carers to deal with the problems they are confronted with in this situation . We aim ed to examine if completion of a self‐directed problem‐solving bibliotherapy by first‐time carers of young people with first‐episode psychosis improved their social problem solving compared with carers who only received treatment as usual . Methods A r and omized controlled trial was carried out through two early intervention psychosis services in Melbourne , Australia . A sample of 124 carers were r and omized to problem‐solving bibliotherapy or treatment as usual . Participants were assessed at baseline , 6‐ and 16‐week follow‐up . Results Intent‐to‐treat analyses were used and showed that recipients of bibliotherapy had greater social problem‐solving abilities than those receiving treatment as usual , and these effects were maintained at both follow‐up time points . Conclusions Our findings affirm that bibliotherapy , as a low‐cost complement to treatment as usual for carers , had some effects in improving their problem‐solving skills when addressing problems related to the care and support of young people with first‐episode psychosis Family interventions for first-episode psychosis ( FEP ) are an integral component of treatment , with positive effects mainly on patients ’ mental state and relapse rate . However , comparatively little attention has been paid to the effects of family interventions on caregivers ’ stress coping and well-being , especially in non-Western countries . We aim ed to test the effects of a 5-month clinician-supported problem-solving bibliotherapy ( CSPSB ) for Chinese family caregivers of people with FEP in improving family burden and carers ’ problem-solving and caregiving experience , and in reducing psychotic symptoms and duration of re-hospitalizations , compared with those only received usual outpatient family support ( UOFS ) . A r and omized controlled trial was conducted across 2 early psychosis clinics in Hong Kong , where there might be inadequate usual family support services for FEP patients . A total of 116 caregivers were r and omly selected , and after baseline measurement , r and omly assigned to the CSPSB or UOFS . They were also assessed at 1-week and 6- and 12-month post-intervention . Intention-to-treat analyses were applied and indicated that the CSPSB group reported significantly greater improvements in family burden and caregiving experience , and reductions in severity of psychotic symptoms and duration of re-hospitalizations , than the UOFS group at 6- and 12-month follow-up . CSPSB produces moderate long-term benefits to caregivers and FEP patients , and is a low-cost adjunct to UOFS This r and omized controlled trial examined the effectiveness of a 12-session mutual support group conducted over 3-months for Chinese family caregivers of a relative with schizophrenia compared with routine family support services in Hong Kong . Forty-eight family caregivers from two psychiatric outpatient clinics were allocated r and omly to an experimental ( mutual support and usual outpatient care ) group ( n = 24 ) or a control ( usual outpatient care only ) group ( n = 24 ) . Data were collected prior to , 1 week and 3 months after the intervention . Families allocated to the mutual support group experienced decreased levels of family burden and increased family functioning and these changes were significantly greater than those of the controls at both post-intervention time points . The experimental group also showed a significant decrease in the duration of patient re-hospitalization ( the total number of days of psychiatric hospitalization ) at 3 months compared with the control group . This suggests that the mutual support group provided a more responsive service for patients than st and ard care . However , there was no significant difference in family service utilization between the two groups . The findings indicate that a mutual support group can provide benefits for family caregivers of people with schizophrenia that go beyond those provided by routine family support OBJECTIVE To investigate whether the beneficial effects of a structured , psychoeducational , parallel-group program for adolescents with early-onset psychosis and their families observed immediately after the intervention were maintained 2 years later . METHOD The present study examines the longitudinal efficacy of a r and omized controlled trial based on a psychoeducational , problem-solving , structured group intervention for adolescents with early-onset psychosis and their families ( PE ) and compares it with that of a nonstructured group intervention ( NS ) after a 2-year follow-up . We analyzed whether the differences between PE and NS found after the intervention persisted 2 years later . Intergroup differences in number and duration of hospitalizations , symptoms , and functioning were also assessed . RESULTS After 2 years of follow-up , we were able to reassess 89 % of patients . In the PE group , 13 % of patients had visited the emergency department , compared with 50 % in the NS group ( p = .019 ) . However , no statistically significant differences were found between the groups for negative symptoms or number and duration of hospitalizations . A significant improvement in Positive and Negative Syndrome Scale ( PANSS ) general symptoms was observed in the PE group . CONCLUSION Our psychoeducational group intervention showed sustained effects by diminishing the number of visits to emergency departments 2 years after the intervention . Our findings indicate that this psychoeducational intervention could provide patients with long-lasting re sources to manage crises more effectively . Clinical trial registration information-Intervention Module AGES ( AGES-CM ) ; http:// clinical trials.gov/ ; NCT02101372 OBJECTIVE This study was conducted to test the effects of a nine-month family-led peer support group for Chinese people with schizophrenia in Hong Kong over a three-year follow-up and to compare outcomes with those of psychoeducation and st and ard psychiatric outpatient care . METHODS A r and omized controlled trial of 106 Chinese families of patients with schizophrenia was conducted between August 2007 and January 2011 in three psychiatric outpatient clinics . Families were r and omly assigned to peer support ( N=35 ) , psychoeducation ( N=35 ) , or st and ard care ( N=36 ) . In addition to st and ard care received , peer support and psychoeducation consisted of 14 two-hour group sessions , with patients participating in six to 14 sessions . Multiple patient and family outcomes --including families ' support service utilization and functioning and patients ' functioning mental state and rehospitalization rate -- were measured at recruitment and one week , 18 months , and 36 months after completion of the interventions . RESULTS Patients and families in the peer support group reported consistently greater improvements over three years in overall functioning ( family p<.005 ; patient p<.001 ) and reductions in duration and number of hospitalizations ( p<.01 for both ) , without any increase in service utilization . CONCLUSIONS Family-led peer support groups were an effective intervention for Chinese people with schizophrenia , result ing in long-term effects of improving patient and family functioning and reducing rehospitalizations BACKGROUND Carers ' satisfaction with psychiatric services related to information and advice is generally poor . This may be particularly true for services trying to meet the needs of ethnically diverse communities . It is important that services attempt to ameliorate carers ' concerns as early as possible . The authors aim ed to assess the impact of a brief educational and advice support service on carers of patients with a first episode of psychotic illness . METHOD Carers of all patients identified with a first episode of psychosis in a defined psychiatric catchment area of North London were invited to participate . Following consent from patients and relatives , relatives were r and omly allocated to receive ( in addition to usual services ) a brief intervention comprising education and advice about the disorder from a support team or to usual care from community psychiatric services . RESULTS One hundred and six carers were recruited to the study . Take-up of the intervention was less than expected and the intervention had little impact . The authors found no differences over time between the r and omized arms for relatives ' satisfaction ( F = 23 , p = 0 .4 , df = 1 ) or number of days spent by patients in hospital over nine months from entry to the trial ( F= 1.7 , p= 0.18 , df = 1 ) . CONCLUSIONS It was found that the support and advice intervention for families had little impact on their satisfaction or on patients ' outcomes . However , failure to take up the intervention threatens the conclusions as the power to show an effect was reduced . Although family interventions , in general , are considered an important adjunct to the treatment of patients with chronic psychosis , there may be difficulties in providing an educational and support intervention shortly after first onset . How and when psychiatric services provide information and advice to carers of people newly diagnosed with a psychosis requires further study BACKGROUND Positive effects on the relapse from illness and compliance with medication by patients have been observed from family intervention for schizophrenia . However , little attention has been paid to the effects on family members , particularly those in non-Western countries . Inconsistent and inconclusive findings were found on the family-related outcomes and longer-term effects of family intervention . OBJECTIVE This study tested the effects of a nine-month family-led mutual support group for Chinese people with schizophrenia , compared with a psycho-education group and st and ard psychiatric care over a 24-month follow-up . DESIGN A r and omised controlled trial [ registered with Clinical Trials.gov ( NCT00940394 ) ] with repeated- measures , three-group design . SETTING S Two regional psychiatric outpatient clinics in Hong Kong . PARTICIPANTS One hundred and thirty-five Chinese family caregivers and their patients with schizophrenia were r and omly recruited , of whom 45 family dyads received family-led mutual support group , a psycho-education group , or st and ard care . METHODS After completing the pre-test question naire , the participants were r and omly assigned into one of the three study groups . The mutual support and psycho-education groups comprised 14 two-hour group sessions , with patients participating in at least 5 sessions . Those in st and ard care ( and two treatment groups ) received routine psychiatric care . Multiple patient and family-related psychosocial outcomes were compared at recruitment and at one week , 12 months , and 24 months following interventions . RESULTS One hundred and twenty-six of 135 family dyads completed the three post-tests and 43 ( 95.6 % ) attended at least nine group sessions ( 60 % ) of the mutual support group programme . Mean ages of the family caregivers in the study ranged from 41.2 ( SD=7.0 ) to 42.7 ( SD=7.6 ) years . About two-thirds of the caregivers were male and patients ' parent or spouse . The results of multivariate analysis of variance followed by Helmert contrasts tests indicated that the participants in the mutual support group indicated significantly greater improvement in family and patient functioning [ F(2 , 132)=5.40 , p=0.005 and F(2 , 132)=6.88 , p=0.001 , respectively ] and social support for families [ F(2 , 131)=5.01 , p=0.005 ] , and in reducing patients ' symptom severity [ F(2 , 132)=4.65 , p=0.01 ] and length of re-hospitalisations [ F(2 , 132)=4.78 , p=0.01 ] at 12- and 24-month follow-ups . CONCLUSIONS Family-led mutual support group for schizophrenia produces longer-term benefits to both the patients ' and families ' functioning and relapse prevention for patients , compared with psycho-education and st and ard care . This group programme can be an effective family intervention for Chinese people with schizophrenia BACKGROUND Carers of young people with first episode psychosis ( FEP ) often face burden . Underst and ing ways in which carers cope is not only important for providing support to them but might maximise patient outcomes . The aim of this study was to examine strategies carers use to cope with the burden of caring for a young person with FEP . METHODS The study was part of a r and omized controlled trial focusing on the effectiveness of a problem-solving bibliotherapy intervention for carers of FEP patients , in terms of promoting coping and reducing psychological distress . Baseline data on the Ways of Coping ( WOC ) scale was available for 124 carers aged between 18 and 66 years . Principal component analysis with PROMAX rotation was used to determine the number of factors that could be used to characterise coping behaviour . Regression analyses were used to determine how the factors were related to carers ' demographics , burden , psychological well-being and expressed emotion . RESULTS Approximately half of the carers reported that they frequently use positive coping techniques such as self-talk , active problem solving , and positive reframing . The factor analysis yielded five factors : ( i ) cognitive-escape coping ; ( ii ) optimistic coping ; ( iii ) seeking connections ; ( iv ) tension reduction ; and ( v ) distancing . The relationships between these factors and demographic characteristics , carers ' perception of burden , expressed emotion , and psychological distress are reported . CONCLUSIONS Avoidance coping strategies are related to psychological distress , emotional over-involvement , and increased carer burden . Interventions facilitating the use of adaptive problem solving and positive re- appraisal will promote carer coping and reduce psychological distress BACKGROUND Family intervention for psychotic disorders is an integral part of psychiatric treatment with positive effects on patients ' mental state and relapse rate . However , the effect of such family-based intervention on caregivers ' psychological distress and well-being , especially in non-Western countries , has received comparatively much less attention . OBJECTIVES To test the effects of guided problem-solving-based manual-guided self-learning programme for family caregivers of adults with recent-onset psychosis over a 6-month period of follow-up , when compared with those in usual family support service . DESIGN A single-centre r and omised controlled trial , which was registered at Clinical Trials.gov ( NCT02391649 ) , with a repeated- measures , two-arm ( parallel-group ) design . SETTING S One main psychiatric outpatient clinic in the New Territories of Hong Kong . PARTICIPANTS A r and om sample of 116 family caregiverss of adult out patients with recent-onset psychosis . METHODS Following pre-test measurement , caregivers were assigned r and omly to one of two study groups : a 5-month self-help , problem-solving-based manual-guided self-learning ( or bibliotherapy ) programme ( in addition to usual care ) , or usual family support service only . Varieties of patient and caregiver health outcomes were assessed and compared at baseline and at 1-week and 6-month post-intervention . RESULTS One hundred and eleven ( 96 % ) caregivers completed the 6-month follow-up ( two post-tests ) ; 55 of them ( 95 % ) completed ≥4 modules and attended ≥2 review sessions ( i.e. , 75 % of the intervention ) . The family participants ' mean age was about 38 years and over 64 % of them were female and patient 's parent or spouse . Multivariate analyses of variance indicated that the manual-guided self-learning group reported significantly greater improvements than the usual care group in family burden [ F(1,110)=6.21 , p=0.006 ] and caregiving experience [ F(1,110)=6.88 , p=0.0004 ] , and patients ' psychotic symptoms [ F(1,110)=6.25 , p=0.0003 ] , functioning [ F(1,110)=7.01 , p=0.0005 ] and number of hospitalisations [ F(1,110)=5.71 , p=0.005 ] over 6-month follow-up . CONCLUSIONS Problem-solving-based , manual-guided self-learning programme for family caregivers of adults with recent-onset psychosis can be an effective self-help programme and provide medium-term benefits to patients ' and caregivers ' mental health and duration of patients ' re-hospitalisations Caring for young people with first-episode psychosis ( FEP ) is challenging and can adversely affect carer well-being , with limited evidence -based support material s available . We aim ed to examine whether completion of a self-directed problem-solving bibliotherapy among carers of young people with FEP led to a better experience of caring , less distress and expressed emotion , and better general health than carers who only received treatment as usual ( TAU ) . A r and omized controlled trial was conducted across two early-intervention psychosis services in Melbourne , Australia . A total of 124 carers were r and omized to problem-solving bibliotherapy intervention ( PSBI ) or TAU and assessed at baseline , 6-week and 16-week follow-up . Intent-to-treat analyses were carried out and indicated that recipients of PSBI had a more favorable experience of caring than those receiving TAU , and these effects were sustained at both follow-up time points . Across the other measures , both groups demonstrated improvements by week 16 , although the PBSI group tended to improve earlier . The PSBI group experienced a greater reduction in negative emotional evaluations of the need to provide additional support to young people with FEP than the TAU group by week 6 , while the level of psychological distress decreased at a greater rate from baseline to 6 weeks in the PSBI compared with the TAU group . These findings support the use of problem-solving bibliotherapy for first-time carers , particularly as a cost-effective adjunct to TAU |
10,322 | 24,148,111 | Transcranial direct current stimulation is likely to be effective in enhancing motor performance in the short term when applied selectively to patients with stroke . | Transcranial direct current stimulation has been gaining increasing interest as a potential therapeutic treatment in stroke recovery .
We performed a systematic review with meta- analysis of r and omized controlled trials to collate the available evidence in adults with residual motor impairments as a result of stroke . | Background . No rehabilitation intervention has effectively improved functional use of the arm and h and in patients with severe upper limb paresis after stroke . Pilot studies suggest the potential for transcranial direct current stimulation and bilateral robotic training to enhance gains . Objective . In a double-blind , r and omized trial the combination of these interventions was tested . Methods . This study r and omized 96 patients with an ischemic supratentorial lesion of 3 to 8 weeks ’ duration with severe impairment of motor control with a Fugl-Meyer score ( FMS ) for the upper limb < 18 into 3 groups . For 6 weeks , group A received anodal stimulation of the lesioned hemisphere , group B received cathodal stimulation of the nonlesioned side for 20 minutes at 2.0 mA , and group C received sham stimulation . The electrodes were placed over the h and area and above the contralateral orbit . Contemporaneously , the subjects practice d 400 repetitions each of 2 different bilateral movements on a robotic assistive device . Results . The groups were matched at onset . The FMS improved in all patients at 6 weeks ( P < .001 ) . No between-group differences were found ; initial versus finish FMS scores were 7.8 ± 3.8 versus 19.1 ± 14.4 in group A , 7.9 ± 3.4 versus 18.8 ± 10.5 in group B , and 8.2 ± 4.4 versus 19.2 ± 15.0 in group C. No significant changes between groups were present at 3 months . Conclusions . Neither anodal nor cathodal transcranial direct current stimulation enhanced the effect of bilateral arm training in this exploratory trial of patients with cortical involvement and severe weakness . Unilateral h and training and upregulation of the nonlesioned hemisphere might also be tried in this population Objective : Motor recovery after stroke depends on the integrity of ipsilesional motor circuits and interactions between the ipsilesional and contralesional hemispheres . In this sham-controlled r and omized trial , we investigated whether noninvasive modulation of regional excitability of bilateral motor cortices in combination with physical and occupational therapy improves motor outcome after stroke . Methods : Twenty chronic stroke patients were r and omly assigned to receive 5 consecutive sessions of either 1 ) bihemispheric transcranial direct current stimulation ( tDCS ) ( anodal tDCS to upregulate excitability of ipsilesional motor cortex and cathodal tDCS to downregulate excitability of contralesional motor cortex ) with simultaneous physical/occupational therapy or 2 ) sham stimulation with simultaneous physical/occupational therapy . Changes in motor impairment ( Upper Extremity Fugl-Meyer ) and motor activity ( Wolf Motor Function Test ) assessment s were outcome measures while functional imaging parameters were used to identify neural correlates of motor improvement . Results : The improvement of motor function was significantly greater in the real stimulation group ( 20.7 % in Fugl-Meyer and 19.1 % in Wolf Motor Function Test scores ) when compared to the sham group ( 3.2 % in Fugl-Meyer and 6.0 % in Wolf Motor Function Test scores ) . The effects outlasted the stimulation by at least 1 week . In the real-stimulation group , stronger activation of intact ipsilesional motor regions during paced movements of the affected limb were found postintervention whereas no significant activation changes were seen in the control group . Conclusions : The combination of bihemispheric tDCS and peripheral sensorimotor activities improved motor functions in chronic stroke patients that outlasted the intervention period . This novel approach may potentiate cerebral adaptive processes that facilitate motor recovery after stroke . Classification of evidence : This study provides Class I evidence that for adult patients with ischemic stroke treated at least 5 months after their first and only stroke , bihemispheric tDCS and simultaneous physical/occupational therapy given over 5 consecutive sessions significantly improves motor function as measured by the Upper Extremity Fugl-Meyer assessment ( raw change treated 6.1 ± 3.4 , sham 1.2 ± 1.0 ) PURPOSE It is thought that following a stroke the contralesional motor region exerts an undue inhibitory influence on the lesional motor region which might limit recovery . Pilot studies have shown that suppressing the contralesional motor region with cathodal transcranial Direct Current Stimulation ( tDCS ) can induce a short lasting functional benefit ; greater and longer lasting effects might be achieved with combining tDCS with simultaneous occupational therapy ( OT ) and applying this intervention for multiple sessions . METHODS We carried out a r and omized , double blind , sham controlled study of chronic stroke patients receiving either 5 consecutive days of cathodal tDCS ( for 30 minutes ) applied to the contralesional motor region and simultaneous OT , or sham tDCS+OT . RESULTS we showed that cathodal tDCS+OT result ed in significantly more improvement in Range-Of-Motion in multiple joints of the paretic upper extremity and in the Upper-Extremity Fugl-Meyer scores than sham tDCS+OT , and that the effects lasted at least one week post-stimulation . Improvement in motor outcome scores was correlated with decrease in fMRI activation in the contralesional motor region exposed to cathodal stimulation . CONCLUSIONS This suggests that cathodal tDCS combined with OT leads to significant motor improvement after stroke due to a decrease in the inhibitory effect that the contralesional hemisphere exerts onto the lesional hemisphere We set out to answer two questions with this study : 1 . Can stroke patients improve voluntary control of their paretic ankle by practising a visuo-motor ankle-tracking task ? 2 . Are practice effects enhanced with non-invasive brain stimulation ? A carefully selected sample of chronic stroke patients able to perform the experimental task attended three data collection sessions . Facilitatory transcranial direct current stimulation ( tDCS ) was applied in a r and om order over the lower limb primary motor cortex of the lesioned hemisphere or the non-lesioned hemisphere or sham stimulation was delivered over the lesioned hemisphere . In each session , tDCS was applied as patients practice d tracking a sinusoidal waveform for 15 min using dorsiflexion – plantarflexion movements of their paretic ankle . The difference in tracking error prior to , and after , the 15 min of practice was calculated . A practice effect was revealed following sham stimulation , and this effect was enhanced with tDCS applied over the lesioned hemisphere . The practice effect observed following sham stimulation was eliminated by tDCS applied over the non-lesioned hemisphere . The study provides the first evidence that non-invasive brain stimulation applied to the lesioned motor cortex of moderate- to well-recovered stroke patients enhances voluntary control of the paretic ankle . The results provide a basis for examining whether this enhanced ankle control can be induced in patients with greater impairments and whether enhanced control of a single or multiple lower limb joints improves hemiparetic gait patterns Recovery of function after a stroke is determined by a balance of activity in the neural network involving both the affected and the unaffected brain hemispheres . Increased activity in the affected hemisphere can promote recovery , while excessive activity in the unaffected hemisphere may represent a maladaptive strategy . We therefore investigated whether reduction of the excitability in the unaffected hemisphere by cathodal transcranial direct current stimulation could result in motor performance improvement in stroke patients . We compared these results with excitability-enhancing anodal transcranial direct current stimulation of the affected hemisphere and sham transcranial direct current stimulation . Both cathodal stimulation of the unaffected hemisphere and anodal stimulation of the affected hemisphere ( but not sham transcranial direct current stimulation ) improved motor performance significantly . These results suggest that the appropriate modulation of bihemispheric brain structures can promote motor function recovery Kim DY , Ohn SH , Yang EJ , Park C-I , Jung KJ : Enhancing Motor Performance by Anodal Transcranial Direct Current Stimulation in Subacute Stroke Patients . Objective : To investigate whether anodal transcranial direct current stimulation enhances motor performance in the paretic h and of subacute poststroke patients and how long the improvement persisted after the session . Design : Ten subacute poststroke patients who suffered stoke within 12 wks were recruited for this single-blinded , sham-controlled , crossover study . Anodal transcranial direct current stimulation or sham stimulation was r and omly delivered on the hot spot of the first dorsal interosseous in the affected hemisphere . The duration of transcranial direct current stimulation was 20 mins and sham was 30 secs. The Box and Block test and finger acceleration measurement were performed before , during , immediately after , and 30 and 60 mins after anodal or sham stimulation to assess time-dependent changes in motor performance . Results : Finger acceleration measurement and Box and Block test were significantly improved after anodal transcranial direct current stimulation compared with sham stimulation ( P < 0.05 ) . Anodal transcranial direct current stimulation significantly improved Box and Block test for at least 60 mins and finger acceleration until 30 mins after stimulation ( P < 0.05 ) without significant differences in attention and fatigue . Conclusions : Anodal transcranial direct current stimulation on the affected hemisphere can enhance motor performance of the hemiparetic h and transiently , outlasting the stimulation session OBJECTIVE Brain polarization in the form of transcranial direct current stimulation ( tDCS ) , which influences motor function and learning processes , has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation . Proper testing in Neurorehabilitation requires double-blind sham-controlled study design s. Here , we evaluated the effects of tDCS and sham stimulation ( SHAM ) on healthy subjects and stroke patients ' self-report measures of attention , fatigue , duration of elicited sensations and discomfort . METHODS tDCS or SHAM was in all cases applied over the motor cortex . Attention , fatigue , and discomfort were self rated by study participants using visual analog scales . Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined . Investigators question ing the patients were blind to the intervention type . RESULTS tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue , and could not be distinguished from SHAM by study participants nor investigators . CONCLUSIONS Successful blinding of subjects and investigators and ease of application simultaneously with training protocol s supports the feasibility of using tDCS in double-blind , sham-controlled r and omized trials in clinical Neurorehabilitation . SIGNIFICANCE tDCS could evolve into a useful tool , in addition to TMS , to modulate cortical activity in Neurorehabilitation Objective : To evaluate whether robot-assisted gait training combined with transcranial direct current stimulation is more effective than robot-assisted gait training alone or conventional walking rehabilitation for improving walking ability in stroke patients . Design : Pilot r and omized clinical trial . Setting : Rehabilitation unit of a university hospital . Subjects : Thirty patients with chronic stroke . Interventions : All patients received ten 50-minute treatment sessions , five days a week , for two consecutive weeks . Group 1 ( n = 10 ) underwent a robot-assisted gait training combined with transcranial direct current stimulation ; group 2 ( n = 10 ) underwent a robot-assisted gait training combined with sham transcranial direct current stimulation ; group 3 ( n = 10 ) performed overground walking exercises . Main measures : Patients were evaluated before , immediately after and two weeks post treatment . Primary outcomes : six-minute walking test , 10-m walking test . Results : No differences were found between groups 1 and 2 for all primary outcome measures at the after treatment and follow-up evaluations . A statistically significant improvement was found after treatment in performance on the six-minute walking test and the 10-m walking test in favour of group 1 ( six-minute walking test : 205.20 ± 61.16 m ; 10-m walking test : 16.20 ± 7.65 s ) and group 2 ( six-minute walking test : 182.5 ± 69.30 m ; 10-m walking test : 17.71 ± 8.20 s ) compared with group 3 ( six-minute walking test : 116.30 ± 75.40 m ; 10-m walking test : 26.30 ± 14.10 s ) . All improvements were maintained at the follow-up evaluation . Conclusions : In the present pilot study transcranial direct current stimulation had no additional effect on robot-assisted gait training in patients with chronic stroke . Larger studies are required to confirm these preliminary findings Kim DY , Lim JY , Kang EK , You DS , Oh MK , Oh BM , Paik NJ : Effect of transcranial direct current stimulation on motor recovery in patients with subacute stroke . Objective : To test the hypothesis that 10 sessions of transcranial direct current stimulation combined with occupational therapy elicit more improvement in motor function of the paretic upper limb than sham stimulation in patients with subacute stroke . Design : Eighteen patients with subacute stroke with h and motor impairment were r and omly assigned to one of the three 10-day sessions of ( a ) anodal transcranial direct current stimulation over the affected motor cortex , ( b ) cathodal transcranial direct current stimulation over the unaffected motor cortex , or ( c ) sham stimulation . Blinded evaluators assessed upper limb motor impairment and global functional state with the Fugl-Meyer Assessment score and the Modified Barthel Index at baseline , 1 day after stimulation , and 6 mos after stimulation . Results : Baseline scores for Fugl-Meyer Assessment and Modified Barthel Index were comparable in all groups ( P > 0.05 ) . At 6-mo follow-up , cathodal transcranial direct current stimulation led to a greater improvement in Fugl-Meyer Assessment than the sham procedure ( P < 0.05 ) . There was a significant inverse correlation between baseline Fugl-Meyer Assessment and Fugl-Meyer Assessment increase at 6 mos ( r = −0.846 ; P < 0.01 ) . Conclusions : Our results suggest a potentially beneficial effect of noninvasive cortical stimulation during rehabilitative motor training of patients who have suffered from subacute strokes Neurophysiological and computer modelling studies have shown that electrode montage is a critical parameter to determine the neuromodulatory effects of transcranial direct current stimulation ( tDCS ) . We tested these results clinical ly by systematic ally investigating optimal tDCS electrode montage in stroke . Ten patients received in a counterbalanced and r and omised order the following conditions of stimulation ( i ) anodal stimulation of affected M1 ( primary motor cortex ) and cathodal stimulation of unaffected M1 ( ‘ bilateral tDCS ’ ) ; ( ii ) anodal stimulation of affected M1 and cathodal stimulation of contralateral supraorbital area ( ‘ anodal tDCS ’ ) ; ( iii ) cathodal stimulation of unaffected M1 and anodal stimulation of contralateral supraorbital area ( ‘ cathodal tDCS ’ ) ; ( iv ) anodal stimulation of affected M1 and cathodal stimulation of contralateral deltoid muscle ( ‘ extra-cephalic tDCS ’ ) and ( v ) sham stimulation . We used the Jebsen – Taylor Test ( JTT ) as a widely accepted measure of upper limb function . Bilateral tDCS , anodal tDCS and cathodal tDCS were shown to be associated with significant improvements on the JTT . Placing the reference electrode in an extracephalic position and use of sham stimulation did not induce any significant effects . This small sham controlled cross-over clinical trial is important to provide additional data on the clinical effects of tDCS in stroke and for planning and design ing future large tDCS trials in patients with stroke |
10,323 | 27,456,352 | Conclusions Little is known about how to improve the implementation of guidelines in nursing homes , and the evidence to support or discourage particular interventions is inconclusive . | Background Research on guideline implementation strategies has mostly been conducted in setting s which differ significantly from a nursing home setting and its transferability to the nursing home setting is therefore limited .
The objective of this study was to systematic ally review the effects of interventions to improve the implementation of guidelines in nursing homes . | Background The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting . Methods Twenty facilities took part in a r and omized controlled trial with a seven month follow-up period . Two outreach visits were delivered by a pharmacist . At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates , psychotropic drug prescribing and stroke risk reduction practice s ( BP monitoring , aspirin and warfarin use ) for the facility relevant to the physician . The effect of the interventions was determined via pre- and post-intervention case note audit . Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications . Chi-square tests , independent sample s t-test , and logistic regression were used in the analysis . Results Data were available from case notes at baseline ( n = 897 ) and seven months follow-up ( n = 902 ) , 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits . Pre- and post-intervention data were available for 715 participants . There were no differences between the intervention and control groups for the three month fall rate . We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention . The exception was significantly greater use of " as required " antipsychotics in the intervention group compared with the control group after the pharmacy intervention ( RR = 4.95 ; 95%CI 1.69–14.50 ) . There was no statistically significant difference between groups for the numbers of patients " at risk of stroke " on aspirin at follow-up . Conclusions While the strategy was well received by the physicians involved , there was no change in prescribing patterns . Patient care in residential setting s is complex and involves contributions from the patient 's physician , family and residential care staff . The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained OBJECTIVE To test the effect of a complex guideline -based intervention on agitation and psychotropic prescriptions . DESIGN , SETTING , PARTICIPANTS Cluster r and omized controlled trial ( VIDEANT ) with blinded assessment of outcome in 18 nursing homes in Berlin , Germany , comprising 304 dementia patients . INTERVENTION Training , support , and activity therapy intervention , delivered at the level of each nursing home , focusing on the management of agitation in dementia . Control group nursing homes received treatment as usual . MEASUREMENTS Levels of agitated and disruptive behavior ( Cohen-Mansfield agitation inventory [ CMAI ] ) as the primary outcome . Number of neuroleptics , antidepressants , and cholinesterase inhibitors ( ChEIs ) prescribed in defined daily dosages ( DDDs ) . RESULTS Of 326 patients screened , 304 ( 93.3 % ) were eligible and cluster-r and omized to 9 intervention ( n = 163 ) and 9 control ( n = 141 ) nursing homes . Data were collected from 287 ( 94.4 % ) patients at 10 months . At 10 months , compared with controls , nursing home residents with dementia in the intervention group exhibited significantly less agitation as measured with the CMAI ( adjusted mean difference , 6.24 ; 95 % CI 2.03 - 14.14 ; P = .009 ; Cohen 's d = 0.43 ) , received fewer neuroleptics ( P < .05 ) , more ChEIs ( P < .05 ) , and more antidepressants ( P < .05 ) . CONCLUSION Complex guideline -based interventions are effective in reducing agitated and disruptive behavior in nursing home residents with dementia . At the same time , increased prescription of ChEIs and antidepressants together with decreased neuroleptic prescription suggests an effect toward guideline -based pharmacotherapy OBJECTIVES To evaluate the effectiveness of efforts to translate and disseminate evidence -based guidelines about atypical antipsychotic use to nursing homes ( NHs ) . DESIGN Three-arm , cluster r and omized trial . SETTING NHs . PARTICIPANTS NHs in the state of Connecticut . MEASUREMENTS Evidence -based guidelines for atypical antipsychotic prescribing were translated into a toolkit targeting NH stakeholders , and 42 NHs were recruited and r and omized to one of three toolkit dissemination strategies : mailed toolkit delivery ( minimal intensity ) ; mailed toolkit delivery with quarterly audit and feedback reports about facility-level antipsychotic prescribing ( moderate intensity ) ; and in-person toolkit delivery with academic detailing , on-site behavioral management training , and quarterly audit and feedback reports ( high intensity ) . Outcomes were evaluated using the Reach , Effectiveness , Adoption , Implementation , Maintenance ( RE- AIM ) framework . RESULTS Toolkit awareness of 30 % ( 7/23 ) of leadership of low-intensity NHs , 54 % ( 19/35 ) of moderate-intensity NHs , and 82 % ( 18/22 ) of high-intensity NHs reflected adoption and implementation of the intervention . Highest levels of use and knowledge among direct care staff were reported in high-intensity NHs . Antipsychotic prescribing levels declined during the study period , but there were no statistically significant differences between study arms or from secular trends . CONCLUSION RE- AIM indicators suggest some success in disseminating the toolkit and differences in reach , adoption , and implementation according to dissemination strategy but no measurable effect on antipsychotic prescribing trends . Further dissemination to external stakeholders such as psychiatry consultants and hospitals may be needed to influence antipsychotic prescribing for NH residents 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 OBJECTIVE To test the effectiveness of using a full-time project nurse to assist residential aged care facilities in using evidence -based approaches to falls injury prevention . DESIGN , SETTING AND PARTICIPANTS Cluster r and omised controlled trial involving 5391 residents in 88 aged care facilities in the Hunter and Lower Mid North Coast areas of New South Wales . Residents were followed for 545 days or until death or discharge . Data were collected from July 2005 to June 2007 . INTERVENTION Employment of a project nurse to encourage best- practice falls injury prevention strategies during the 17-month intervention period . MAIN OUTCOME MEASURES Monthly data about falls , falls injury and falls injury prevention programs ; audit of hospitalisation for fractured neck of femur . RESULTS Despite significant increases in the provision of hip protectors and use of vitamin D supplementation in both intervention and control facilities , there was no difference in the number of falls or falls injuries between the intervention and control groups , nor a reduction in falls overall . There was also no difference between the 7-month pre-intervention period and the intervention period in the number of falls or falls injuries . Factors related to residents having an increased risk of falls with fractured neck of femur included being ambulant , having dementia , increasing age , and having a high falls risk assessment score . CONCLUSION It is difficult to change falls risk among high-risk population s , including people with dementia . The use of important strategies such as hip protectors and vitamin D and calcium supplementation increased during the study , probably with contamination of control facilities . Longer follow-up may be required to measure the impact on falls outcomes of the strategy of using a facilitating nurse . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry ACTRN12605000540617 In this prospect i ve cluster r and omized controlled trial we evaluated the impact of short-term provision of enhanced infection control support on infection control practice in nursing homes in South London . Twelve nursing homes were recruited , six each in intervention ( 300 residents ) and control ( 265 residents ) groups . Baseline observations of h and hygiene facilities , environmental cleanliness and safe disposal of clinical waste showed poor compliance in both groups . Post-intervention observations showed improvement in both groups . There was no statistical difference between the two groups in the compliance for h and hygiene facilities ( P=0.69 ) ; environmental cleanliness ( P=0.43 ) and safe disposal of clinical waste ( P=0.96 ) . In both groups , greatest improvement was in compliance with safe disposal of clinical waste and the least improvement was in h and hygiene facilities . Since infection control practice improved in intervention and control groups , we could not demonstrate that provision of short-term , enhanced , infection control support in nursing homes had a significant impact in infection control practice BACKGROUND Pain prevalence in nursing homes remains high , with multiple resident , staff , and physician barriers presenting serious challenges to its improvement . AIMS The study aims were to ( 1 ) develop and test a multifaceted , culturally competent intervention to improve nursing home pain practice s ; ( 2 ) improve staff , resident , and physician knowledge and attitudes about pain and its management ; ( 3 ) improve actual pain practice s in nursing homes ; and ( 4 ) improve nursing home policies and procedures related to pain . METHODS A multifaceted , culturally competent intervention was developed and tested in six Colorado nursing homes , with another six nursing homes serving as control sites . Both educational and behavioral change strategies were employed . FINDINGS The intervention was successful in improving the percentage of residents reporting constant pain in the treatment homes . Context ual factors ( implementation of Medicare 's Nursing Home Compare report card ) appeared to exert a positive influence on pain documentation . There was no reduction in the percentage of residents reporting pain or reporting moderate/severe pain . DISCUSSION Multiple challenges to quality improvement exist in nursing homes . Turnover of nursing staff reduced actual exposure to the intervention , and turnover of directors of nursing influenced constancy of message and overall facility stability . Residents often failed to report their pain , and physicians were reluctant to alter their prescribing practice s. IMPLICATION S Any intervention to improve pain management in nursing homes must target explicitly the residents , nursing home staff , and primary care physicians . Implementation strategies need to accommo date the high turnover rates among staff , as well as the changes among the nursing home leadership . CONCLUSIONS Pain is a complex problem in the nursing home setting . Multiple factors must be considered in both the design and implementation of interventions to improve pain practice s and reduce pain prevalence in nursing homes BACKGROUND Frail older people admitted to nursing homes are at risk of a range of adverse outcomes , including pressure ulcers . Clinical decision support systems are believed to have the potential to improve care and to change the behaviour of healthcare professionals . OBJECTIVES To determine whether a multi-faceted tailored strategy to implement an electronic clinical decision support system for pressure ulcer prevention improves adherence to recommendations for pressure ulcer prevention in nursing homes . DESIGN Two-armed r and omized controlled trial in a nursing home setting in Belgium . The trial consisted of a 16-week implementation intervention between February and June 2010 , including one baseline , four intermediate , and one post-testing measurement . Primary outcome was the adherence to guideline -based care recommendations ( in terms of allocating adequate pressure ulcer prevention in residents at risk ) . Secondary outcomes were the change in resident outcomes ( pressure ulcer prevalence ) and intermediate outcomes ( knowledge and attitudes of healthcare professionals ) . SETTING R and om sample of 11 wards ( 6 experimental ; 5 control ) in a convenience sample of 4 nursing homes in Belgium . PARTICIPANTS In total , 464 nursing home residents and 118 healthcare professionals participated . METHODS The experimental arm was involved in a multi-faceted tailored implementation intervention of a clinical decision support system , including interactive education , reminders , monitoring , feedback and leadership . The control arm received a hard-copy of the pressure ulcer prevention protocol , supported by st and ardized 30 min group lecture . RESULTS Patients in the intervention arm were significantly more likely to receive fully adequate pressure ulcer prevention when seated in a chair ( F=16.4 , P=0.003 ) . No significant improvement was observed on pressure ulcer prevalence and knowledge of the professionals . While baseline attitude scores were comparable between both groups [ exp . 74.3 % vs. contr . 74.5 % ( P=0.92 ) ] , the mean score after the intervention was 83.5 % in the experimental group vs. 72.1 % in the control group ( F=15.12 , P<0.001 ) . CONCLUSION The intervention was only partially successful to improve the primary outcome . Attitudes improved significantly while the knowledge of the healthcare workers remained unsatisfactorily low . Further research should focus on the underlying reasons for these findings OBJECTIVES To compare two strategies for implementing guidelines for nursing home-acquired pneumonia ( NHAP ) and to measure outcomes associated with treatment in accordance with the guidelines . DESIGN R and omized controlled trial . SETTING Ten skilled nursing facilities ( SNFs ) from a single metropolitan area . PARTICIPANTS Patients with an episode of pneumonia acquired more than 3 days after admission to SNF ( N = 350 ) : 226 preintervention episodes of pneumonia and 116 postintervention episodes . INTERVENTIONS Multi-faceted education intervention including small-group consensus process limited to physicians and a similar intervention that included physicians and nurses within r and omly selected SNFs . MEASUREMENTS Antibiotic use at diagnosis compared with the guidelines , hospital admission , severity of pneumonia , and 30-day mortality . RESULTS Data were complete for 344 episodes of NHAP . For the preintervention group ( n = 226 ) , 62.2 % ( 79/127 ) of the episodes were treated with parenteral antibiotics ( PA ) when PA were recommended by the guidelines and 57.6 % ( 57/99 ) of episodes were treated with oral antibiotics ( OA ) when OA were indicated by the guidelines . Postintervention , treatment with PA and OA according to the guidelines was not significantly different between the two groups of r and omized SNFs . A multivariate analysis comparing PA use pre- and postintervention for all SNFs , adjusted for variation in the frequency and severity of pneumonia , found significantly more of the postintervention episodes were treated with PA in accordance with the guidelines ( P < .02 ) . A preintervention significant difference in 30-day mortality observed between episodes with indications for PA ( 37.8 % ( 48/127 ) ) and episodes with indications for OA ( 6.1 % ( 6/99 ) ) ( P < .001 ) was not present postintervention ( 11.5 % ( 6/52 ) ; ( 23.8 % ( 15/64 ) ; P = .06 ) . There was no significant difference in 30-day mortality preintervention and postintervention for episodes with guideline indications for OA ( P = .35 ) or for PA ( P = .05 ) ( P = .16 for multivariate analysis ) . The difference in PA use was not associated with significant differences in hospital admissions for episodes on NHAP . CONCLUSION The increase in the use of PA provides evidence that care within SNFs can be significantly changed using st and ard quality improvement techniques . Use of the guidelines did not significantly affect mortality . The addition of a practical severity of NHAP model or a change in reimbursement structure may enhance the guidelines ' impact on hospitalization for NHAP . The financial benefits available with use of the guidelines will be limited unless the guidelines contribute to a reduction in rates of hospitalization 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 Patient care guidelines are usually implemented one at a time , yet patients are at risk for multiple , often preventable , adverse events simultaneously . OBJECTIVE The SAFE or SORRY ? programme targeted three adverse events ( pressure ulcers , urinary tract infections and falls ) and was successful in reducing the incidence of these events . This article explores the process of change and describes the effect on the preventive care given . DESIGN Separate data on preventive care were collected along the cluster r and omised trial , which was conducted between September 2006 and November 2008 . SETTING S Ten hospital wards and ten nursing home wards . PARTICIPANTS We monitored nursing care given to adult patients with an expected length of stay of at least five days . METHODS The SAFE or SORRY ? programme consisted of the essential recommendations of guidelines for pressure ulcers , urinary tract infections and falls . A multifaceted implementation strategy was used to implement this multiple guidelines programme . Data on preventive care given to patients were collected in line with these guidelines and the difference between the intervention and the usual care group at follow-up was analysed . RESULTS The study showed no overall difference in preventive pressure ulcer measures between the intervention and the usual care group in hospitals ( estimate=6 % , CI : -7 - 19 ) and nursing homes ( estimate=4 % , CI : -5 - 13 ) . For urinary tract infections , even statistically significantly fewer hospital patients at risk received preventive care ( estimate=19 % , CI : 17 - 21 ) . For falls in hospitals and nursing homes , no more patients at risk received preventive care . CONCLUSION Though the SAFE OR SORRY ? programme effectively reduced the number of adverse events , an increase in preventive care given to patients at risk was not demonstrated . These results seem to emphasise the difficulties in measuring the compliance to guidelines . More research is needed to explore the possibilities for measuring the implementation of multiple guidelines using process indicators Background Unrelieved pain among nursing home ( NH ) residents is a well-documented problem . Attempts have been made to enhance pain management for older adults , including those in NHs . Several evidence -based clinical guidelines have been published to assist providers in assessing and managing acute and chronic pain in older adults . Despite the proliferation and dissemination of these practice guidelines , research has shown that intensive systems-level implementation strategies are necessary to change clinical practice and patient outcomes within a health-care setting . One promising approach is the embedding of guidelines into explicit protocol s and algorithms to enhance decision making . Purpose The goal of the article is to describe several issues that arose in the design and conduct of a study that compared the effectiveness of pain management algorithms coupled with a comprehensive adoption program versus the effectiveness of education alone in improving evidence -based pain assessment and management practice s , decreasing pain and depressive symptoms , and enhancing mobility among NH residents . Methods The study used a cluster-r and omized controlled trial ( RCT ) design in which the individual NH was the unit of r and omization . The Roger ’s Diffusion of Innovations theory provided the framework for the intervention . Outcome measures were surrogate-reported usual pain , self-reported usual and worst pain , and self-reported pain-related interference with activities , depression , and mobility . Results The final sample consisted of 485 NH residents from 27 NHs . The investigators were able to use a staggered enrollment strategy to recruit and retain facilities . The adaptive r and omization procedures were successful in balancing intervention and control sites on key NH characteristics . Several strategies were successfully implemented to enhance the adoption of the algorithm . Limitations /Lessons The investigators encountered several method ological challenges that were inherent to both the design and implementation of the study . The most problematic issue concerned the measurement of outcomes in persons with moderate to severe cognitive impairment . It was difficult to identify valid , reliable , and sensitive outcome measures that could be applied to all NH residents regardless of the ability to self-report . Another challenge was the inability to incorporate advances in implementation science into the ongoing study Conclusions Method ological challenges are inevitable in the conduct of an RCT . The need to optimize internal validity by adhering to the study protocol is compromised by the emergent logistical issues that arise during the course of the study OBJECTIVES To assess the impact of a hygiene-encouragement program on reducing infection rates ( primary end point ) by 5 % . DESIGN A cluster r and omized study was carried out over a 5-month period . SETTING S AND PARTICIPANTS Fifty nursing homes ( NHs ) with 4345 beds in France were r and omly assigned by stratified-block r and omization to either a multicomponent intervention ( 25 NHs ) or an assessment only ( 25 NHs ) . INTERVENTION The multicomponent intervention was targeted to caregivers and consisted of implementing a bundle of infection prevention consensual measures . Interactive educational meetings using a slideshow were organized at the intervention NHs . The NHs were also provided with color posters emphasizing h and hygiene and a kit that included hygienic products such as alcoholic-based h and sanitizers . Knowledge surveys were performed periodically and served as reminders . MEASUREMENTS The primary end point was the total infection rate ( urinary , respiratory , and gastrointestinal infections ) in those infection cases classified either as definite or probable . Analyses corresponded to the underlying design and were performed according to the intention-to-treat principle . This study was registered ( # NCT01069497 ) . RESULTS Forty-seven NHs ( 4515 residents ) were included and followed . The incidence rate of the first episode of infection was 2.11 per 1000 resident-days in the interventional group and 2.15 per 1000 resident-days in the control group ; however , the difference between the groups did not reach statistical significance in either the unadjusted ( Hazard Ratio [ HR ] = 1.00 [ 95 % confidence interval ( CI ) 0.89 - 1.13 ] ; P = .93 ] ) or the adjusted ( HR = 0.99 [ 95 % CI 0.87 - 1.12 ] ; P = .86 ] ) analysis . CONCLUSION Disentangling the impact of this type of intervention involving behavioral change in routine practice in caregivers from the prevailing environmental and context ual determinants is often complicated and confusing to interpret the results OBJECTIVE To compare a supervised versus a non-supervised implementation of an oral health care guideline in Fl and ers ( Belgium ) . BACKGROUND The key factor in realising good oral health is daily oral hygiene care . In 2007 , the Dutch guideline ' Oral health care in care homes for elderly people ' was developed to improve oral health of institutionalised elderly . MATERIAL S AND METHODS A r and om sample of 12 nursing homes was r and omly allocated to the intervention or the control group . Representative sample s of 30 residents in each home were monitored during a 6-month study period . The intervention included a supervised implementation of the guideline . RESULTS At the 6-month follow-up , only a small but statistically significant ( p = 0.002 ) beneficial effect ( 0.32 ) of the intervention was observed for denture plaque after adjustment for baseline value and the r and om effect of the institution . In the linear mixed regression models , including a r and om institution effect , difference in denture plaque level was no longer statistically significant at the 5 % level . CONCLUSION Only denture hygiene has been improved by the supervised implementation , although with lower benefits than presumed . Factors on institutional level , difficult to assess quantitatively , may play an important role in the final result Background : Despite three decades of empirical investigation into research utilization and a renewed emphasis on evidence -based medicine and evidence -based practice in the past decade , underst and ing of factors influencing research uptake in nursing remains limited . There is , however , increased awareness that organizational influences are important . Objectives : To develop and test a theoretical model of organizational influences that predict research utilization by nurses and to assess the influence of varying degrees of context , based on the Promoting Action on Research Implementation in Health Services ( PARIHS ) framework , on research utilization and other variables . Methods : The study sample was drawn from a census of registered nurses working in acute care hospitals in Alberta , Canada , accessed through their professional licensing body ( n = 6,526 nurses ; 52.8 % response rate ) . Three variables that measured PARIHS dimensions of context ( culture , leadership , and evaluation ) were used to sort cases into one of four mutually exclusive data sets that reflected less positive to more positive context . Then , a theoretical model of hospital- and unit-level influences on research utilization was developed and tested , using structural equation modeling , and 300 cases were r and omly selected from each of the four data sets . Results : Model test results were as follows-low context : & khgr;2 = 124.5 , df = 80 , p < . 001 ; partially low : & khgr;2 = 144.2 , p < . 001 , df = 80 ; partially high : & khgr;2 = 157.3 , df = 80 , p < . 001 ; and partially low : & khgr;2 = 146.0 , df = 80 , p < . 001 . Hospital characteristics that positively influenced research utilization by nurses were staff development , opportunity for nurse-to-nurse collaboration , and staffing and support services . Increased emotional exhaustion led to less reported research utilization and higher rates of patient and nurse adverse events . Nurses working in context s with more positive culture , leadership , and evaluation also reported significantly more research utilization , staff development , and lower rates of patient and staff adverse events than did nurses working in less positive context s ( i.e. , those that lacked positive culture , leadership , or evaluation ) . Conclusion : The findings highlight the combined importance of culture , leadership , and evaluation to increase research utilization and improve patient safety . The findings may serve to strengthen the PARIHS framework and to suggest that , although it is not fully developed , the framework is an appropriate guide to implement research into practice OBJECTIVE To evaluate the impact of regular multidisciplinary team interventions on the quantity and quality of psychotropic drug prescribing in Swedish nursing homes . DESIGN A r and omized controlled trial . SETTING A sample of 33 nursing homes : 15 experimental homes and 18 control homes representing 5 % of all Swedish nursing homes . PARTICIPANTS The sample consisted of 1854 long-term care residents with an average age of 83 years . Seventy percent of the residents were women , and 42 % had a documented diagnosis of dementia . An additional 5 % had a psychotic disorder , and 7 % had a diagnosis of depression . INTERVENTION Experimental homes participated in an outreach program that was design ed to influence drug use through improved teamwork among physicians , pharmacists , nurses , and nurses ' assistants . Multidisciplinary team meetings were held on a regular basis throughout the 12-month study period . MEASUREMENTS Lists of each resident 's prescriptions were collected 1 month before and 1 month after the 12-month intervention . Measures included the proportion of residents with any psychotropic drug , polymedicine , and therapeutic duplication and proportion of residents with nonrecommended and acceptable drugs in each psychotropic drug class , as defined by current Swedish guidelines . RESULTS Baseline results show extensive psychotropic drug prescribing , with the most commonly prescribed drugs being hypnotics ( 40 % ) , anxiolytics ( 40 % ) , and antipsychotics ( 38 % ) . After 12 months of team meetings in the experimental homes , there was a significant decrease in the prescribing of psychotics ( -19 % ) , benzodiazepine hypnotics ( -37 % ) , and antidepressants ( -59 % ) . Orders for more acceptable antidepressants also increased in the experimental homes . In the control homes there was increased use of acceptable antidepressants , but there were no significant reductions in other drug classes . CONCLUSIONS There is excessive prescription of psychotropic drugs in Swedish nursing homes . Improved teamwork among caregivers can improve prescribing as defined by clinical guidelines BACKGROUND Use of restraint amongst institutionalised elderly with dementia and problem behaviour not only remains widespread , but also appears to be accepted as inevitable . OBJECTIVE The aim of this study was to reduce problem behaviour and the use of restraint in demented patients using a staff training program as intervention . METHODS The study was a r and omised single-blind controlled trial and took place in Stavanger , Norway . Four nursing homes were r and omised to a control or an intervention group after stratification for size . The intervention consisted of a full day seminar , followed by a one-hour session of guidance per month over six months . The content of the educational program focused on the decision making process in the use of restraint and alternatives to restraint consistent with professional practice and quality care . The primary outcome measures were number of restraints per patient in the nursing homes in one week and agitation as measured with the Brief Agitation Rating Scale ( BARS ) . These were rated before and immediately after the intervention was completed . The assessment s were performed blind to design and r and omisation group . RESULTS Clinical and demographic variables did not differ between the intervention and control groups at baseline . After the intervention period , the number of restraints had declined by 54 % in the treatment group , and increased by 18 % in the control group . The difference between the two groups was statistically significant ( p = 0.013 ) . There was a trend towards higher BARS score in the intervention compared to the control group at follow up ( p = 0.052 ) . CONCLUSION Although the level of agitated behaviour remained unchanged or increased slightly , the educational program led to a significant reduction of the use of restraint in institutionalised elderly with dementia . These results suggest that educational programs can improve the quality of care of people with dementia OBJECTIVE To study the effects of introducing a nursing guideline on depression in residents with dementia of psychogeriatric nursing home wards . METHODS A multi-center controlled clinical trial with r and omization at ward level was used to study the effects of the guideline introduction . Nursing teams were trained in applying the guideline to their own residents diagnosed with depression in dementia . Key elements of the nursing guideline are increasing individualized pleasant activities and decreasing unpleasant events . Participating residents were 97 residents diagnosed with dementia and comorbid depression , from 18 psychogeriatric nursing home wards , in 9 Dutch nursing homes . Measurements took place at pre-test , post-test and follow-up . Primary outcome was severity of depression measured with the MDS/RAI-Depression Rating Scale ( DRS ) and the Cornell Scale for Depression in Dementia . Secondary outcome is mood as measured by the FACE-observation scale . RESULTS Compliance with the nursing guideline was moderate . Despite this , residents on the experimental wards showed a significant reduction in depression on the DRS . With the Cornell scale a reduction of depression was found as well , although not significantly different from that in the control group . No effects on observed mood were found . CONCLUSION This study shows significant reductions in depression severity by introducing a nursing guideline on psychogeriatric nursing home wards . Better compliance with the guideline could probably enlarge the effects . Some ways to achieve enhanced compliance are : ( 1 ) additionally train non-certified nurse assistants , and ( 2 ) emphasize necessary conditions for successful introduction of the guideline to nursing team managers OBJECTIVE To determine the effectiveness of different types of interventions in improving health professional performance and health outcomes . DATA SOURCES MEDLINE , SCI SEARCH , CINAHL and the Research and Development Re source Base in CME were search ed for trials of educational interventions in the health care professions published between 1970 and 1993 inclusive . STUDY SELECTION Studies were selected if they provided objective measurements of health professional performance or health outcomes and employed r and om or quasi-r and om allocation methods in their study design s to assign individual subjects or groups . Interventions included such activities as conferences , outreach visits , the use of local opinion leaders , audit and feedback , and reminder systems . DATA EXTRACTION Details extracted from the studies included the study design ; the unit of allocation ( e.g. , patient , provider , practice , hospital ) ; the characteristics of the targeted health care professionals , educational interventions and patients ( when appropriate ) ; and the main outcome measure . DATA SYNTHESIS The inclusion criteria were met by 102 trials . Areas of behaviour change included general patient management , preventive services , prescribing practice s , treatment of specific conditions such as hypertension or diabetes , and diagnostic service or hospital utilization . Dissemination-only strategies , such as conferences or the mailing of unsolicited material s , demonstrated little or no changes in health professional behaviour or health outcome when used alone . More complex interventions , such as the use of outreach visits or local opinion leaders , ranged from ineffective to highly effective but were most often moderately effective ( result ing in reductions of 20 % to 50 % in the incidence of inappropriate performance ) . CONCLUSION There are no " magic bullets " for improving the quality of health care , but there are a wide range of interventions available that , if used appropriately , could lead to important improvements in professional practice and patient outcomes BACKGROUND Patient care guidelines are usually implemented one at a time , yet patients are at risk for multiple , often preventable , adverse events simultaneously . OBJECTIVE This study aim ed to test the effect of the SAFE or SORRY ? programme on the incidence of three adverse events ( pressure ulcers , urinary tract infections and falls ) . This paper describes Part I of the study : the effect on the incidence of adverse events . DESIGN A cluster r and omised trial was conducted between September 2006 and November 2008 . After a three-month baseline period the intervention was implemented followed by a nine-month follow-up period . SETTING S Ten wards from four hospitals and ten wards from six nursing homes were stratified for institute and ward type and then r and omised to intervention or usual care group . PARTICIPANTS During baseline and follow-up , patients ( ≥18 years ) with an expected length of stay of at least five days , were asked to participate . METHODS The SAFE or SORRY ? programme consisted of the essential recommendations of guidelines for the three adverse events . A multifaceted implementation strategy was used for the implementation : education , patient involvement and feedback on process and outcome indicators . The usual care group continued care as usual . Data were collected on the incidence of adverse events and a Poisson regression model was used to estimate the rate ratio of the adverse events between the intervention and the usual care group at follow-up . RESULTS At follow-up , 2201 hospital patients with 3358 patient weeks and 392 nursing home patients with 5799 patient weeks were observed . Poisson regression analyses showed a rate ratio for the development of an adverse event in favour of the intervention group of 0.57 ( 95 % CI : 0.34 - 0.95 ) and 0.67 ( 95 % CI : 0.48 - 0.99 ) for hospital patients and nursing home patients respectively . CONCLUSION This study showed that implementing multiple guidelines simultaneously is possible , which is promising . Patients in the intervention groups developed 43 % and 33 % fewer adverse events compared to the usual care groups in hospitals and nursing homes respectively . Even so , more research is necessary to underline these results . TRIAL REGISTRATION clinical trials.gov , number NCT00365430 |
10,324 | 26,630,545 | There is evidence that different non-pharmacological interventions can be used with preterms , neonates , and older infants to significantly manage pain behaviors associated with acutely painful procedures .
The most established evidence was for non-nutritive sucking , swaddling/facilitated tucking , and rocking/holding .
There are significant gaps in the existing literature on non-pharmacological management of acute pain in infancy | BACKGROUND Infant acute pain and distress is commonplace .
Infancy is a period of exponential development .
Unrelieved pain and distress can have implication s across the lifespan .
This is an up date of a previously published review in the Cochrane Data base of Systematic Review s , Issue 10 2011 entitled ' Non-pharmacological management of infant and young child procedural pain ' .
OBJECTIVES To assess the efficacy of non-pharmacological interventions for infant and child ( up to three years ) acute pain , excluding kangaroo care , and music . | We previously demonstrated that local massage for one minute can enhance immunogenicity of diphtheria , tetanus , and whole-cell pertussis ( DTPw ) vaccination . This study further analyzes the effects of more intense local manipulation on infants after DTPw and DTPa ( diphtheria , tetanus , and acellular pertussis ) vaccination . A total of 808 infants aged two months were recruited to be vaccinated with either DTPw or DTPa . Vaccinees in both groups were further divided into two groups ; those receiving local manipulation ( massage and hot packing after vaccinations ) and those receiving only vaccinations . Results showed that safety profiles were largely similar between those who had local manipulation following vaccination and those without . The only significant difference was more frequent local reactions including pain and swelling following the first two doses in both the DTPa and DTPw groups receiving manipulation compared with the groups not receiving manipulation . Serologic tests revealed that local manipulation had no significant effect on antibody response to pertussis toxin and filamentous hemagglutinin , and diphtheria and tetanus toxins . The effect of local massage on DTPw was related to the intensity of local massage . Too vigorous a local manipulation caused adverse local reactions and no beneficial effect on antibody response . As for the infants receiving DTPa and local massages for two minutes with hot packing , no significant effect on either the reactogenicity or immunogenicity was found AIMS This study examined the effectiveness of non-nutritive sucking on preterm infant pain , changes in infant behaviour and frequency of abnormal physiological signals during heel stick procedures in Taiwan . BACKGROUND Preterm infants ' repetitive exposure to painful procedures may result in changes to brain organisation . Pain management should be a priority in neonatal care . DESIGN R and omised control trial . METHODS Preterm infants ( gestational age 28.9 - 37 weeks ) were r and omised to two groups : those receiving ( experimental , n = 52 ) or not receiving non-nutritive sucking ( control , n = 52 ) during heel stick procedures . Pain was measured before ( for three minutes ) , during and after ( during 10-minute recovery ) heel stick procedures by the Premature Infant Pain Profile , changes in infant behaviour and abnormal physiological parameters . Results . Infants in both groups had similar odds ratios for pain and moderate-to-severe pain ( 0.57 and 0.58 , respectively ) , after adjusting for time effects , postconceptional age , heel stick duration , painful experiences and baseline Premature Infant Pain Profile score . The pain scores of infants with non-nutritive sucking were significantly lower than those of non-nutritive sucking infants at all eight phases of the heel stick procedures . Infants undergoing heel stick procedures in the experimental group had lower rates ratios for ' grimace ' and ' h and to mouth or face ' behaviours than control infants ( 0.73 and 0.78 , respectively ) . CONCLUSION Non-nutritive sucking effectively reduced pain , particularly mild to moderate pain and behavioural responses to pain in infants receiving heel stick procedures , suggesting that nurses can offer this intervention to relieve pain in preterm infants undergoing invasive procedures . RELEVANCE TO CLINICAL PRACTICE Infants should be given an appropriate-sized pacifier for comfort during painful procedures . Nurses need to be informed about the effectiveness of non-nutritive sucking , its analgesic mechanisms and how to use and incorporate it into practice OBJECTIVE To test the efficacy of maternal skin-to-skin contact , or kangaroo care ( KC ) , on diminishing the pain response of preterm neonates to heel lancing . DESIGN A crossover design was used , in which the neonates served as their own controls . Subjects Preterm neonates ( n = 74 ) , between 32 and 36 weeks ' postmenstrual age and within 10 days of birth , who were breathing without assistance and who were not receiving sedatives or analgesics in 3 level II to III neonatal intensive care units in Canada . INTERVENTIONS In the experimental condition , the neonate was held in KC for 30 minutes before the heel-lancing procedure and remained in KC for the duration of the procedure . In the control condition , the neonate was in the prone position in the isolette . The ordering of conditions was r and om . MAIN OUTCOME MEASURES The primary outcome was the Premature Infant Pain Profile , which is composed of 3 facial actions , maximum heart rate , and minimum oxygen saturation changes from baseline in 30-second blocks . Videotapes , taken with the camera positioned on the neonate 's face so that an observer could not tell whether the neonate was being held or was in the isolette , were coded by research assistants who were naïve to the purpose of the study . Heart rate and oxygen levels were continuously monitored into a computer for later analysis . A repeated- measures analysis of covariance was used , with order of condition and site as factors and severity of illness as a covariate . RESULTS Premature Infant Pain Profile scores across the first 90 seconds from the heel-lancing procedure were significantly ( .002<P<.04 ) lower by 2 points in the KC condition . CONCLUSIONS For preterm neonates who are 32 weeks ' postmenstrual age or older , KC seems to effectively decrease pain from heel lancing . Further study is needed to determine if younger neonates or those requiring assistance in breathing , or older infants or toddlers , would benefit from KC , or if it would remain effective over several procedures . Given its effectiveness , and that parents of neonates in critical care units want to participate more in comforting their children , KC is a potentially beneficial strategy for promoting family health This experiment had three goals : 1 . To identify the basis of sucking-induced analgesia in healthy , term , newborn humans undergoing the painful , routine , procedure of heel lance and blood collection . 2 . To evaluate how taste-induced and sucking-induced analgesias combine to combat pain . 3 . To determine whether facial grimacing was an accurate index of diminished pain , or whether it was linked to tissue trauma . We report that : 1 . Sucking an unflavored pacifier was analgesic when and only when suck rate exceeded 30 sucks/min . 2 . The combination of sucrose and nonnutritive sucking was remarkably analgesic ; we saw no behavioral indication in nine of the ten infants that the heel lance had even occurred . 3 . Grimacing was reduced to almost naught by procedures that essentially eliminated crying and markedly reduced heart rate during the blood harvesting procedure Background Co-bedding , a developmental care strategy , is the practice of caring for diaper clad twins in one incubator ( versus separating and caring for each infant in separate incubators ) , thus creating the opportunity for skin-to-skin contact and touch between the twins . In studies of mothers and their infants , maternal skin-to-skin contact has been shown to decrease procedural pain response according to both behavioral and physiological indicators in very preterm neonates . It is uncertain if this comfort is derived solely from maternal presence or from stabilization of regulatory processes from direct skin contact . The intent of this study is to compare the comfort effect of co-bedding ( between twin infants who are co-bedding and those who are not ) on infant pain response and physiologic stability during a tissue breaking procedure ( heelstick ) . Methods / Design Medically stable preterm twin infants admitted to the Neonatal Intensive Care Unit will be r and omly assigned to a co-bedding group or a st and ard care group . Pain response will be measured by physiological and videotaped facial reaction using the Premature Infant Pain Profile scale ( PIPP ) . Recovery from the tissue breaking procedure will be determined by the length of time for heart rate and oxygen saturation to return to baseline . Sixty four sets of twins ( n = 128 ) will be recruited into the study . Analysis and inference will be based on the intention-to-treat principle . Discussion If twin contact while co-bedding is determined to have a comforting effect for painful procedures , then changes in current neonatal care practice s to include co-bedding may be an inexpensive , non invasive method to help maintain physiologic stability and decrease the long term psychological impact of procedural pain in this high risk population . Knowledge obtained from this study will also add to existing theoretical models with respect to the exact mechanism of comfort through touch . Trial registration OBJECTIVE . The role of laparoscopic surgery in pediatric inguinal hernia repair is unclear . We aim ed to compare day-case laparoscopic hernia repair with open repair . METHODS . A prospect i ve , single-blinded r and omized study in children aged 4 months to 16 years with unilateral inguinal hernia was performed . The primary outcome measure was the time to normal daily activities after surgery . Secondary outcome measures included postoperative pain , time in the operation room , results , and complications . RESULTS . Eighty-nine patients were enrolled ( laparoscopic hernia repair : 47 , open repair : 42 ) . The mean number of days to normal activity after laparoscopic hernia repair and open repair was 2.4 and 2.5 , respectively . Thirty-seven ( 79 % ) patients with laparoscopic hernia repair and 20 ( 42 % ) with open repair required rescue analgesia postoperatively . The median pain score in the second postoperative morning was significantly higher after laparoscopic hernia repair . The median times in the operation room for laparoscopic hernia repair and open repair were 63 and 38 minutes , respectively . Surgical and cosmetic results were similar at up to 2 years ' follow-up . CONCLUSIONS . Recovery and outcome were similar after open repair and laparoscopic hernia repair in children . Laparoscopic hernia repair was associated with increased theater time and postoperative pain BACKGROUND : Suprapubic aspiration ( SPA ) and urine catheterization ( UC ) are performed frequently in preterm neonates to rule out urinary tract infection ; however , a comparison of the pain caused by both procedures has not been made previously . OBJECTIVE : To compare pain responses in preterm infants who are undergoing urine collection by using SPA versus UC . METHODS : Prospect i ve , single-blind , r and omized clinical trial was conducted in 2 NICUs . Preterm infants who required urine sample s for microbiologic analysis were r and omly assigned to undergo either SPA or UC . The infants ' facial and physiologic responses were videotaped during the procedure and later scored by a research assistant who was blind to the method of urine collection . The primary outcome measure was facial-grimacing during the procedure , which was assessed by measuring the percentage of time the infants displayed brow-bulging . Secondary outcomes included changes in heart rate ( beats per minute ) , oxygen saturation ( % ) , and procedural success rate . RESULTS : Forty-eight preterm infants participated . Characteristics did not differ ( P > .05 ) between groups . The mean ( SD ) percent brow-bulging score was higher in the SPA group than in the UC group ( 67 % [ 34 ] vs 42 % [ 38 ] ; P = .02 ) . Heart rate and oxygen saturation did not differ ( P = .50 and .74 , respectively ) . The procedure-success rate , although lower in the SPA group , was not statistically different ( 60 % vs 78 % ; P = .17 ) . CONCLUSIONS : SPA was more painful than UC , as assessed by brow-bulging , and had a tendency to be associated with a higher rate of procedure failure . These findings should be taken into consideration when choosing between these 2 procedures for preterm infants who undergo urine sampling OBJECTIVES : Cobedding of preterm twin infants provides tactile , olfactory , and auditory stimulation and may affect pain reactivity . We carried out a r and omized trial to assess the effect of cobedding on pain reactivity and recovery in preterm twin neonates . METHODS : Stable preterm twins ( n = 67 sets ) between 28 and 36 weeks of gestational age were r and omly assigned to a cobedding group ( cared for in the same incubator or crib ) or a st and ard care group ( cared for in separate incubators or cribs ) . Pain response ( determined by the Premature Infant Pain Profile [ PIPP ] ) and time to return to physiologic baseline parameters were compared between groups with adjustment for the nonindependence of twin infants . RESULTS : Maternal and infant characteristics were not significantly different between twin infants in the cobedding and st and ard care groups except for 5-minute Apgar < 7 and postnatal age and corrected gestational age on the day of the heel lance . Mean PIPP scores were not different between groups at 30 , 60 , or 120 seconds . At 90 seconds , mean PIPP scores were higher in the cobedding group ( 6.0 vs 5.0 , P = .04 ) . Recovery time was shorter in the cobedding group compared with the st and ard care group , ( mean = 75.6 seconds versus 142.1 seconds , P = .001 ) . No significant adverse events were associated with cobedding . Adjustment for nonindependence between twins and differences in baseline characteristics did not change the results . CONCLUSIONS : Cobedding enhanced the physiologic recovery of preterm twins undergoing heel lance , but did not lead to lower pain scores The objective of this study was to compare the effects of containment and swaddling on premature infants ' heart rates ( HR ) , oxygen saturation ( SpO(2 ) , and the Premature Infant Pain Profile ( PIPP ) scores after heelstick . The study used a cross-over experimental design , 32 premature infants with gestational age < 37 weeks , bodyweight < or= 2500 grams , and no diagnosis of congenital heart disease , deformity , sepsis or < or= Grade 3 intraventricular hemorrhage were selected as subjects . Each subject was r and omly assigned to containment or swaddling once while undergoing two heelsticks in different time periods . Heart rate , oxygen saturation , facial expression and PIPP score were recorded from 5 minutes before to 11 minutes after heelstick . According to the paired t test , the results showed ( 1 ) . that mean HR was higher and mean SpO(2 ) was lower than their respective baseline values under the two interventions after heelstick ( p < .05 ) , and that premature infants in swaddling returned to their baseline HR and SpO(2 ) values in shorter time periods compared to those in containment , though the variations of HR and SpO(2 ) between the two interventions exhibited no significant differences ; and ( 2 ) . that pain responses to heelstick under swaddling yielded lower scores than those under containment according to the total PIPP scores , but significant difference between the two interventions was only found at the 3rd and 7th minute . As a whole , there is little difference between the effects of swaddling and containment on attenuating physiological and behavioral stress caused by acute pain . The results of this study can serve as an evidence basis for nursing interventions in acute pain for premature infants . In clinical practice , containment and swaddling can be administered interchangeably according to patients ' individual differences OBJECTIVE To compare operative time , intraoperative and postoperative bleeding and pain using two different techniques for tonsillectomy : electronic molecular resonance bipolar tonsillectomy and blunt dissection tonsillectomy . METHODS From January 2005 to December 2006 , a prospect i ve , r and omised study was performed in 800 children , aged from 3 to 10 years , admitted to the ENT ( Ear Nose Throat ) Unit of Giannina Gaslini Institute , Genoa , Italy to undergo tonsillectomy . Patients were r and omised into two surgical groups , Group A ( electronic molecular resonance tonsillectomy , EMRBT ) and Group B ( blunt dissection tonsillectomy ) . Operative time , intraoperative blood loss and postoperative complications were recorded . During 10 days after surgery , children and their parents were also asked to provide a rating of the patients ' current pain intensity using a visual analogue scale . In this period , the parents were also asked to note the analgesic drugs administered . RESULTS Duration of surgery and blood loss were significantly much lower in the group undergoing electronic molecular resonance bipolar tonsillectomy ( p<0.0001 ) . Postoperative pain scores result ed significantly different between the two methods on days 5 ( p=0.05 ) and 8 ( p=0.001 ) in evaluations by mothers . Moreover , in evaluations by patients pain scores result ed significantly different between the two methods on days 3 ( p=0.02 ) , 8 ( p=0.005 ) and 9 ( p=0.01 ) . We found no difference between boys and girls in pain scores in the 10 days considered , nor between children older than 5 yrs and children younger than or aged 5 years . No statistically significant differences between the two techniques were found in the use of analgesics in all postoperative evaluations . CONCLUSIONS This study showed that the use of electronic molecular resonance bipolar tonsillectomy , compared to blunt dissection , has several advantages . Reduced operative time and intraoperative bleeding make EMRBT more cost effective and allow an increased number of operations . Concerning postoperative pain , the two techniques did not present significant differences in the use of analgesics . The number of postoperative bleeding episodes was also similar in the two groups of patients Fifty-four pediatric cancer patients were studied to determine the relative efficacy of two forms of behavioral intervention for reducing chemotherapy-related distress . Following baseline assessment , subjects were r and omly assigned to receive either hypnosis , non-hypnotic distraction/relaxation , or attention placebo ( control ) during the subsequent identical chemotherapy course . Observational and interview measures of anticipatory and postchemotherapy nausea , vomiting , distress , and functional disruption served as outcome data . Results indicated that treatment condition was the single best predictor of change from baseline to intervention , with children in the hypnosis group reporting the greatest reduction of both anticipatory and postchemotherapy symptoms . The cognitive distraction/relaxation intervention appeared to have a maintenance effect in which symptoms did not get much worse or much better , while children in the control group had symptoms that consistently became worse over time . Emetic potential of the chemotherapy and the prophylactic use of antiemetics each appeared to contribute to the overall severity of symptoms . While the efficacy of hypnosis in the management of chemotherapy distress is supported , the complexities of interacting biologic and psychologic factors are highlighted Background Lumbar punctures ( LPs ) are common in children with cancer . Although pain management during the lumbar puncture has been well st and ardized , dealing with stress and anxiety is not well addressed yet . Our objective was to evaluate the potential improvement of the LP success rate using a positioning pillow , to ensure maximum lumbar flexion , and allow paravertebral muscles to relax , in children who are awake , with either conscious sedation or no sedation . Methods Children aged 2–18 years undergoing LP were r and omly assigned to a positioning pillow or no intervention . The primary outcome was the rate of success , i.e. achieving the LP ( sampling or injection ) at the first attempt , without bleeding ( RBC < 50/mm3 ) . The secondary outcomes included : the child 's pain , assessed by a self-administered visual analogical scales ( VAS ) for children over 6 years of age ; the parents ' and caregivers ' perception of the child 's pain ; the satisfaction of the children , the parents , the caregivers and the physician . The child 's cooperation and the occurrence of post-LP syndrome were also evaluated . Results 124 children ( 62 in each group ) were included . The LP pillow tended to increase the success rate of LPs ( 67 % vs. 57 % , p = 0.23 ) , and decreased the post-LP syndromes ( 15 % vs. 24 % , p = 0.17 ) but the differences were not statistically significant . In children over 6-year of age ( n = 72 ) , the rate of success was significantly higher in the pillow group ( 58.5 % vs. 41.5 % , p = 0.031 ) , with a tendency to feel less pain ( median VAS 25 vs. 15 mm , p = 0.39 ) and being more satisfied ( 84.4 % vs. 75.0 % , p = 0.34 ) . Conclusion Overall results do not demonstrate a benefit in using this pillow for lumbar punctures . This study results also suggest a benefit in the sub group of children over 6-year of age ; this result needs confirmation . Trial Registration The trial was registered with Clinical Trials.gov ( number NCT00775112 ) BACKGROUND Heel stick is the most common painful procedure for preterm infants in neonatal intensive care units . Result ant pain causes adverse physiological effects in major organ systems . Kangaroo Care ( KC ) , involving mother-infant skin-to-skin contact is a promising analgesic for infant pain ; however , the effect of KC on the autonomic nervous system 's response to pain is unknown . AIM To determine if KC results in improved balance in autonomic responses to heel stick pain than the st and ard method where infants remain in an incubator care ( IC ) for the heel stick . STUDY DESIGN A r and omized cross-over trial . SUBJECTS Fourteen preterm infants , 30 - 32 weeks gestational age and less than 9 days postnatal age . OUTCOME MEASURES Infant behavioral state , heart rate , heart rate variability ( HRV ) indices including low frequency ( LF ) and high frequency ( HF ) power , and the LF/HF ratio measured over Baseline , Heel Warming , Heel Stick , and Recovery periods in KC and IC conditions . RESULTS HRV differences between KC and IC were that LF was higher in KC at Baseline ( p<.01 ) and at Heel Stick ( p<.001 ) , and HF was higher in KC at Baseline than in the IC condition ( p<.05 ) . The LF/HF ratio had less fluctuation across the periods in KC than in IC condition and was significantly lower during Recovery in KC than in IC ( p<.001 ) . CONCLUSIONS Infants experienced better balance in response in KC than IC condition as shown by more autonomic stability during heel stick . KC may be helpful in mediating physiologic response to painful procedures in preterm infants We examined responses of preterm infants to swaddling after a heel lance . Fifteen preterm infants from two postconceptional age ( PCA ) groups ( Group 1 : n = 7 , PCA < 31 wk ; Group 2 : n = 8 , PCA ≥ 31 wk ) were observed for 30 minutes during blood sampling followed by routine care ; blood sampling followed by swaddling ; and no blood sampling and routine care . In both groups , blood sampling result ed in concurrent increases in heart rate and state of arousal , in negative facial displays , and in reductions in blood oxygen-saturation . After the blood was drawn , infants less than 31 weeks PCA exhibited an immediate and spontaneous return to behavioral patterns similar to those observed during the no-blood- sample condition , regardless of treatment condition . Infants 31 weeks PCA or older exhibited protracted behavioral disturbance that was significantly reduced by the use of swaddling . We discuss the significance of these findings The objective of this study was to test the efficacy and suitability of virtual reality ( VR ) as a pain distraction for pediatric intravenous ( i.v . ) placement . Twenty children ( 12 boys , 8 girls ) requiring i.v . placement for a magnetic resonance imaging/computed tomography ( MRI/CT ) scan were r and omly assigned to two conditions : ( 1 ) VR distraction using Street Luge ( 5DT ) , presented via a head-mounted display , or ( 2 ) st and ard of care ( topical anesthetic ) with no distraction . Children , their parents , and nurses completed self-report question naires that assessed numerous health-related outcomes . Responses from the Faces Pain Scale-Revised indicated a fourfold increase in affective pain within the control condition ; by contrast , no significant differences were detected within the VR condition . Significant associations between multiple measures of anticipatory anxiety , affective pain , i.v . pain intensity , and measures of past procedural pain provided support for the complex interplay of a multimodal assessment of pain perception . There was also a sufficient amount of evidence supporting the efficacy of Street Luge as a pediatric pain distraction tool during i.v . placement : an adequate level of presence , no simulator sickness , and significantly more child- , parent- , and nurse-reported satisfaction with pain management . VR pain distraction was positively endorsed by all reporters and is a promising tool for decreasing pain , and anxiety in children undergoing acute medical interventions . However , further research with larger sample sizes and other routine medical procedures is warranted Background Skin-to-skin contact , or kangaroo mother care ( KMC ) has been shown to be efficacious in diminishing pain response to heel lance in full term and moderately preterm neonates . The purpose of this study was to determine if KMC would also be efficacious in very preterm neonates . Methods Preterm neonates ( n = 61 ) between 28 0/7 and 31 6/7 weeks gestational age in three Level III NICU 's in Canada comprised the sample . A single-blind r and omized crossover design was employed . In the experimental condition , the infant was held in KMC for 15 minutes prior to and throughout heel lance procedure . In the control condition , the infant was in prone position swaddled in a blanket in the incubator . The primary outcome was the Premature Infant Pain Profile ( PIPP ) , which is comprised of three facial actions , maximum heart rate , minimum oxygen saturation levels from baseline in 30-second blocks from heel lance . The secondary outcome was time to recover , defined as heart rate return to baseline . Continuous video , heart rate and oxygen saturation monitoring were recorded with event markers during the procedure and were subsequently analyzed . Repeated measures analysis -of-variance was employed to generate results . Results PIPP scores at 90 seconds post lance were significantly lower in the KMC condition ( 8.871 ( 95%CI 7.852–9.889 ) versus 10.677 ( 95%CI 9.563–11.792 ) p < .001 ) and non-significant mean differences ranging from 1.2 to1.8 . favoring KMC condition at 30 , 60 and 120 seconds . Time to recovery was significantly shorter , by a minute(123 seconds ( 95%CI 103–142 ) versus 193 seconds ( 95%CI 158–227 ) . Facial actions were highly significantly lower across all points in time reaching a two-fold difference by 120 seconds post-lance and heart rate was significantly lower across the first 90 seconds in the KMC condition . Conclusion Very preterm neonates appear to have endogenous mechanisms elicited through skin-to-skin maternal contact that decrease pain response , but not as powerfully as in older preterm neonates . The shorter recovery time in KMC is clinical ly important in helping maintain homeostasis . Trial Registration ( Current Controlled Trials ) IS RCT PURPOSE Premature infants lack the tactile stimulation they would have otherwise experienced in the womb . Infant massage is a developmentally supportive intervention that has been documented for several decades to have a positive effect on both full term and preterm infants . The purpose of this study was to assess the short and long term benefits of massage on stable preterm infants . METHODS A quasi experimental design was used , 66 infants were recruited from two university hospitals with tertiary level NICUs ; 32 infants received the massage therapy by their mothers . Data collection by a research er blind to the infants ' group assignments included weight at discharge , pain responses on the PIPP scale at discharge , length of stay in hospital , neuro-developmental outcome ( Bayley scores ) and breastfeeding duration at 12 months corrected age . RESULTS Infants who were massaged had significantly lower scores on the PIPP after a heel-stick compared to before the massage and had lower PIPP scores at discharge compared to the control group . Massaged infants had higher cognitive scores at 12 months corrected age . Weight gain , length of stay , breastfeeding duration and motor scores did not differ between groups . CONCLUSION Stable preterm infants benefit from massage therapy given by their mothers and may be a culturally acceptable form of intervention to improve the outcomes of preterm infants PURPOSE The purpose of this study was to identify the effects of Yakson therapy as a pain management tool on the physiologic and behavioral responses of infants with a painful heelstick procedure . METHOD Infants were r and omly assigned to a group that underwent a series of Yakson therapy and a control that received nothing before a heelstick . Heart rate , oxygen saturation , and NIPS were compared between the experimental ( n=16 ) and control ( n=16 ) infants during an undisturbed baseline and after a st and ard heelstick procedure . Yakson therapy consisted of laying a h and on the back , and caressing the abdomen by h and for 5 minutes . RESULT The pain scores of the Yakson group were lower than the control group . For oxygen saturation , there were statistically significant differences between groups . For heart rate , there were no statistically significant differences between groups . CONCLUSION This data suggests that Yakson therapy had a pain relief effect in behavior responses and SaO2 . Accordingly , Yakson therapy should be used as a nursing intervention for simple pain management for a heel prick AIM To compare the efficacies of non-nutritive sucking and glucose solution as pain-relief interventions for neonates undergoing a venipuncture procedure . BACKGROUND Neonates may be subjected to painful procedures . The individual efficacies of non-nutritive sucking or oral glucose solution used alone on pain-relief for neonates still remain controversial . DESIGN A r and omised , parallel-group controlled trial was design ed . METHODS A total of 105 neonates were r and omly assigned to one of the three groups : non-nutritive sucking , glucose solution , or control group . When a neonate underwent a venipuncture during a newborn screening test , his/her pain manifestations were videotaped and subsequently measured using the Neonatal Infant Pain Scale . Both the stability analysis and the analysis of repeated relationships were performed by generalised estimating equations . RESULTS The level of pain was regressed over the study variables ( time and group ) and covariate ( gestational age ) . Both the non-nutritive sucking and glucose solution groups had significantly lower pain scores than the control group during the venipuncture and recovery phases . Furthermore , non-nutritive sucking seemed to be more effective than glucose solution . CONCLUSION Nurses can use a pain assessment tool and the pain-relief intervention to improve the quality of neonatal care in clinical practice . This study indicates that either non-nutritive sucking or glucose solution can effectively decrease the level of pain . RELEVANCE TO CLINICAL PRACTICE If a painful procedure on neonates is inevitable , simple , convenient and effective pain-relief methods such as non-nutritive sucking or glucose solution can be provided alone . Based on a neonate 's condition , nurses can provide 2 ml of 25 % glucose solution through a syringe for a breastfeeding infant before an invasive procedure if nipple confusion is the concern OBJECTIVE To compare the effects of two pediatric venipuncture distress-management distraction strategies that differed in the degree to which they required children 's interaction . METHODS Eighty-eight 1- to 7-year-old children receiving venipuncture were r and omly assigned to one of three treatment conditions : interactive toy distraction , passive movie distraction , or st and ard care . Distress was examined via parent , nurse , self-report ( children over 4 years ) , and observational coding . Engagement in distraction was assessed via observational coding . RESULTS Children in the passive condition were more distracted and less distressed than children in the interactive condition . Although children in the interactive condition were more distracted than st and ard care children , there were no differences in distress between these groups . CONCLUSIONS Despite literature that suggests that interactive distraction should lower distress more than passive distraction , results indicate that a passive strategy might be most effective for children 's venipuncture . It is possible that children 's distress interfered with their ability to interact with the distractor BACKGROUND : To measure the analgesic effectiveness of the 5 S ’s ( swaddling , side/stomach position , shushing , swinging , and sucking ) alone and combined with sucrose , during routine immunizations at 2 and 4 months . METHODS : We conducted a prospect i ve , r and omized , placebo-controlled trial with 2- and 4-month-old infants during well-child visits . Patients were assigned into 4 groups ( 2 × 2 ) receiving either 2 mL of water or 2 mL of 24 % oral sucrose and then either st and ard-of-care comfort measures by parents or intervention with the 5 S ’s immediately postvaccination . The Modified Riley Pain Score was used to score the infants ’ pain at 15-second intervals for 2 minutes , then every 30 seconds up to 5 minutes postvaccination . Repeated- measures analysis of variance examined between group differences and within-subject variability of treatment effect on overall pain scores and length of crying . RESULTS : Two hundred thirty infants were enrolled . Results revealed significantly different mean pain scores between study groups with the exception of the 5S ’s and 5S ’s with sucrose groups . These 2 groups had lower similar mean scores over time , followed by sucrose alone , then control . The same trend was found with the proportion of children crying as with the mean pain score outcome measure . CONCLUSIONS : Physical intervention of the 5 S ’s ( swaddling , side/stomach position , shushing , swinging , and sucking ) provided decreased pain scores on a vali date d pain scale and decreased crying time among 2- and 4-month-old infants during routine vaccinations . The use of 5S ’s did not differ from 5S ’s and sucrose This study aim ed to determine the effects of audiovisual distraction on pain in children during laceration repair in emergency room setting s. This study was design ed as a r and omized controlled trial . Eighty-four children aged 3 - 10 years were r and omized to either the experimental group or the control group . Pain response was assessed by the Faces Pain Rating Scale , a visual analogue scale and the Procedure Behaviour Checklist . We measured salivary cortisol levels as a physiological pain response . The results showed that the sensory and affective pain responses were significantly lower in magnitude in the experimental group than in the control group . There was no statistically significant difference in physiological pain responses between the two groups . Audiovisual distraction might be a helpful method to reduce children 's pain during laceration repair in emergency room setting A total of 50 premature infants ( 25 in KC group , 25 in control group ) were included in this comparative , r and omized , controlled study . Gestational and postnatal ages of the infants were between 26 - 36 weeks and 0 - 28 days , respectively . Infants with congenital abnormalities or sepsis and those who needed mechanical ventilation or surgical intervention were not included in the study . None of the infants received narcotic analgesics . Behavioral and physiologic responses to pain were recorded and Premature Infant Pain Profile ( PIPP ) was used to evaluate the severity of pain . Collected data was evaluated using SPSS for Windows 11.5 program . Premature Infant Pain Profile scores were significantly lower at each measurement during or soon after the invasive procedure in infants in the KC group compared to controls . In conclusion , KC starting 30 minutes before and continuing 10 minutes after an invasive procedure was found to be effective in decreasing pain during and after the invasive procedure in premature infants AIMS AND OBJECTIVES The aim of this study was to evaluate if discomfort levels are statistically significant when two different topical and intraurethral precatheterisation analgesia strategies are used . The primary objective of this research project was to examine methods to decrease pain experienced by paediatric cystogram patients . BACKGROUND Paediatric patients undergoing urinary catheterisations frequently report discomfort . To alleviate catheterisation discomfort in children , some institutions have either used sedation techniques or topical analgesia strategies . St and ardisation of topical anaesthetic application prior to paediatric urinary catheterisation has not been demonstrated in the research literature . DESIGN A prospect i ve , single-blind , r and omised , controlled trial . METHODS The trial was performed with infants and children aged two months-eight years . The first group received one application of lidocaine five minutes prior to catheterisation . The control group received two applications , spaced five minutes apart prior to catheterisation . The FLACC pain score , as the primary outcome variable , was assessed at the time of the catheterisation . Secondary outcome variables including pre- and postcatheterisation heart rate and parental perception were also measured . CONCLUSIONS Two hundred children between two months-eight years of age were r and omly assigned for study inclusion with 91 patients enrolled into the two application groups and 109 patients into the single application group . No statistically significant differences ( p = 0.779 ) in the mean FLACC pain score at the time of the catheterisation between the intervention ( single application ) group ( mean = 3.30 ) and the control ( two application ) group ( mean = 3.39 ) , heart rate or parental perceptions were observed . RELEVANCE TO CLINICAL PRACTICE Topical and intraurethral lidocaine analgesia strategies prior to urinary catheterisation provide an important tool in reducing discomfort for paediatric patients undergoing urinary catheterisation procedures . This study confirms that multiple applications of intraurethral lidocaine gel add little additional benefits in reducing discomfort over single intraurethral application techniques BACKGROUND Despite an increasing awareness regarding pain management in neonates and the availability of published guidelines for the treatment of procedural pain , preterm neonates experience pain leading to short- and long-term detrimental effects . OBJECTIVE To assess the frequency of use of analgesics in invasive procedures in neonates and the associated pain burden in this population . METHODS For 151 neonates , we prospect ively recorded all painful procedures , including the number of attempts required , and analgesic therapy used during the first 14 days of neonatal intensive care unit admission . These data were linked to estimates of the pain of each procedure , obtained from the opinions of experienced clinicians . RESULTS On average , each neonate was subjected to a mean + /- SD of 14 + /- 4 procedures per day . The highest exposure to painful procedures occurred during the first day of admission , and most procedures ( 63.6 % ) consisted of suctioning . Many procedures ( 26 of 31 listed on a question naire ) were estimated to be painful ( pain scores > 4 on a 10-point scale ) . Preemptive analgesic therapy was provided to fewer than 35 % of neonates per study day , while 39.7 % of the neonates did not receive any analgesic therapy in the neonatal intensive care unit . CONCLUSIONS Clinicians estimated that most neonatal intensive care unit procedures are painful , but only a third of the neonates received appropriate analgesic therapy . Despite the accumulating evidence that neonatal procedural pain is harmful , analgesic treatment for painful procedures is limited . Systematic approaches are required to reduce the occurrence of pain and to improve the analgesic treatment of repetitive pain in neonates Background Although sucrose has been accepted as an effective analgesic agent for procedural pain in neonates , previous studies are largely in the NICU population using the procedure of heel lance . This is the first report of the effect of sucrose , pacifier or the combination thereof for the procedural pain of venipuncture in infants in the pediatric emergency department population . Methods The study design was a double ( sucrose ) and single blind ( pacifier ) , placebo-controlled r and omized trial – factorial design carried out in a pediatric emergency department . The study population was infants , aged 0 – 6 months . Eighty-four patients were r and omly assigned to one of four groups : a ) sucrose b ) sucrose & pacifier c ) control d ) control & pacifier . Each child received 2 ml of either 44 % sucrose or sterile water , by mouth . The primary outcome measure : FLACC pain scale score change from baseline . Secondary outcome measures : crying time and heart rate change from baseline . Results Sucrose did not significantly reduce the FLACC score , crying time or heart rate . However sub-group analysis revealed that sucrose had a much greater effect in the younger groups . Pacifier use reduced FLACC score ( not statistically significant ) , crying times ( statistically significant ) but not heart rate . Subgroup analysis revealed a mean crying time difference of 76.52 seconds ( p < 0.0171 ) ( 0–1 month ) and 123.9 seconds ( p < 0.0029 ) ( 1–3 month ) . For subgroup age > 3 months pacifier did not have any significant effect on crying time . Age adjusted regression analysis revealed that both sucrose and pacifier had significant effects on crying time . Crying time increased with both increasing age and increasing gestational age . Conclusion Pacifiers are inexpensive , effective analgesics and are easy to use in the PED for venipuncture in infants aged 0–3 months . The benefits of sucrose alone as an analgesic require further investigation in the older infant , but sucrose does appear to provide additional benefit when used with a pacifier in this age group . Trial registration Current Controlled Trials IS RCT PURPOSE To determine if a recording of a mother 's voice talking soothingly to her baby is useful in diminishing pain in newborns born between 32 and 36 weeks ' gestational age ( GA ) during routine painful procedures . BACKGROUND While maternal skin-to-skin contact has been proven efficacious for diminishing procedural pain in both full-term and preterm neonates , it is often not possible for mothers to be present during a painful procedure . Because auditory development occurs before the third trimester of gestation , it was hypothesized that maternal voice could substitute for maternal presence and be effective in diminishing pain response . SUBJECTSPreterm infants between 32 and 36 weeks ' GA ( n = 20 ) in the first 10 days of life admitted to 2 urban university-affiliated neonatal intensive care units . DESIGN AND METHODS Crossover design with r and om ordering of condition . Following informed consent , an audio recording of the mother talking soothingly to her baby was filtered to simulate the mother 's voice traveling through amniotic fluid . A final 10-minute recording of repetition of mothers ' talking was recorded with maximum peaks of 70 decibels ( dB ) and played at levels ranging between 60 and 70 ambient decibels ( dbA ) , selected above recommendations of the American Academy of Pediatrics in order to be heard over high ambient noise in the setting s. This was played to her infant by a portable cassette tape player 3 times daily during a 48-hour period after feedings ( gavage , bottle , or breast ) . At the end of 48 hours when blood work was required for clinical purpose s , using a crossover design , the infant underwent the heel lancing with or without the recording being played . The order of condition was r and omized , and the second condition was within 10 days . The Premature Infant Pain Profile ( PIPP ) was used as primary outcome . This is a composite measure using heart rate , oxygen saturation , 3 facial actions , behavioral state , and gestational age . This measure has demonstrated reliability and validity indexes . RESULTS There were no significant differences between groups on the PIPP or any of the individual components of the PIPP except a lower oxygen saturation level in the voice condition following the procedure . The second condition , regardless of whether it was voice or control , had higher heart rate scores and lower oxygen saturation scores even in the prelance baseline and warming phases . Order did not affect PIPP scores or facial actions . CONCLUSIONS Different modalities of maternal presence would appear to be necessary to blunt pain response in infants , and recorded maternal voice alone is not sufficient . The loudness of the recording may have obliterated the infant 's ability to discern the mother 's voice and may even have been aversive , reflected in decreased oxygen saturation levels in the voice condition . Preterm neonates of 32 to 36 weeks ' gestation may become sensitized to painful experiences and show anticipatory physiological response This study investigated a behavioral intervention incorporating parent coaching , attentional distraction , and positive reinforcement to control child distress during invasive cancer treatment . Children ( N = 23 ) requiring physical restraint to complete venipuncture were alternately assigned to either a behavioral intervention or an attention control condition . Child distress behaviors were recorded , and self-reports of parent , child , and nurse distress were obtained . Parent and nurse also rated child distress . Results of planned comparisons indicate that observed child distress , parent-rated child distress , and parent ratings of his/her own distress were significantly reduced by behavioral intervention and were maintained across the course of three intervention trials . The use of physical restraint to manage child behavior was also significantly reduced . Child self-reported pain and nurse ratings of child distress were not significantly affected ABSTRACT . We assessed the effectiveness of an odor ( familiar or unfamiliar ) in soothing healthy full-term newborns undergoing a routine heel stick . Forty-four breast-fed newborns were r and omly assigned to one of four groups : Before the heel stick , Group 1 was naturally familiarized with their mother 's milk odor , Group 2 was familiarized with a vanilla smell , and Groups 3 and 4 did not received any familiarization . During and after the heel stick , Group 1 was presented with their mother 's milk odor , Group 2 was presented with the familiar vanilla , Group 3 was presented with an unfamiliar odor , and Group 4 was a control group . Infants ' crying , grimacing , and head movements were analyzed before , during , and after the heel stick . Results show that infants who smelled a familiar odor ( their mother 's milk or vanilla ) cried and grimaced significantly less during the recovery phase compared with the heel stick phase . Infants who were presented with an unfamiliar odor or no odor showed no significant changes during recovery . Moreover , infants who smelled their mother 's milk exhibited significantly less motor agitation during the heel stick compared with the other groups . These findings indicate that smelling a familiar odor reduces agitation during the heel stick and diminishes distress after the procedure OBJECTIVES : To evaluate the efficacy of Floseal as a hemostatic sealant compared to traditional electrocautery hemostasis after cold knife adenotonsillectomy . STUDY DESIGN : Prospect i ve , r and omized , controlled trial of 68 consecutive patients undergoing cold steel adenotonsillectomy . Patients were r and omized to receive either Floseal ( FS ) or electrocautery ( EC ) for hemostasis . RESULTS : FS patients had shorter operative times than EC patients ( 16 min vs 31.2 min , P < 0.0001 ) and less blood loss ( 49.2 mL vs 70.8 mL , P < 0.05 ) . Four EC patients were crossed over to Floseal when adequate hemostasis could not be achieved in the adenoid bed . No Floseal patients were crossed over . FS patients had significantly less pain on postoperative days two through 11 ( P < 0.05 ) and less use of narcotic pain medications over the first 10 postoperative days ( P < 0.05 ) . FS patients also had a faster return to regular diet ( 5.5 days vs 7.9 days , P < 0.01 ) and activity ( 5.3 days vs 7.8 days , P < 0.01 ) as compared to the EC patients . There were no significant complications in either group . CONCLUSIONS : Floseal is safe and efficacious , and decreases postoperative morbidity as compared to electrocautery hemostasis after cold steel adenotonsillectomy . SIGNIFICANCE : This study demonstrates the safety and efficacy of Floseal as a hemostatic method in children undergoing adenotonsillectomy OBJECTIVE To evaluate the pain in healthy newborns requiring blood test by a heel-prick procedure and compare different pain management methods . PATIENTS AND METHOD We studied 150 term infants , in three r and omised groups , from the Maternity Unit of our Hospital for a period of three months . The first group of 50 newborns , received no specific analgesic intervention during blood tests , except our usual nursing intervention ( " facilitated tucking " ) . The second and third group ( 50 newborns ) , received non-nutritive sucking-placebo and non-nutritive sucking-24 % sucrose respectively . RESULTS In the control group , the average score on the scale of discomfort was 3.92 , moderate pain , causing a crying time of 51.72 seconds ; the group receiving a non-nutritive sucking-placeboscored 2.1 , slight pain , 10.68 seconds crying , while the group receiving non-nutritive sucking-24 % sucrose , expressed a level of discomfort of 1.5 points , slight , with an average crying time of 10.70 seconds . The comparative results between the control group and groups of non-nutritive sucking on placebo and 24 % sucrose , both showed significant differences in the scores of the scale of discomfort , as well as in the time crying ( p < 0.001 ) . The comparative analysis between groups of non-nutritive sucking sucrose and placebo showed no significant differences . CONCLUSIONS The blood test by heel lance represents a painful procedure of moderate intensity capable of analgesic treatment . A proper nursing method , along with a complement of non-nutritive sucking during extraction , significantly decreases the discomfort and crying , it being unnecessary to consider other analgesics OBJECTIVE Inadequate assessment of pain in premature infants is a persistent clinical problem . The objective of this research was to develop and vali date a measure for assessing pain in premature infants that could be used by both clinicians and research ers . DESIGN The Premature Infant Pain Profile ( PIPP ) was developed and vali date d using a prospect i ve and retrospective design . Indicators of pain were identified from clinical experts and the literature . Indicators were retrospectively tested using four existing data sets . PATIENTS AND SETTING S Infants of varying gestational ages undergoing different painful procedures from three different setting s were utilized to develop and vali date the measure . METHODS AND RESULTS The largest data set ( n = 124 ) was used to develop the PIPP . The development process included determining the factor structure of the data , developing indicators and indicator scales and establishing internal consistency . The remaining three data sets were utilized to establish beginning construct validity . CONCLUSIONS The PIPP is a newly developed pain assessment measure for premature infants with beginning content and construct validity . The practicality and feasibility for using the PIPP in clinical practice will be determined in prospect i ve research in the clinical setting Manipulated experimentally mothers ' verbal behavior during a routine intramuscular injection in order to help clarify the role of nonprocedural talk ( distraction ) and parental reassurance on children 's reaction to the injection . 42 child-mother dyads were recruited from a general pediatric primary care clinic and were r and omly assigned to a parental reassurance , parental nonprocedural talk ( distraction ) or minimal-treatment control group . Children in the maternal distraction condition exhibited significantly less distress during the immunization injection than those in the reassurance and control conditions . Specifically , children in the maternal distraction group exhibited less crying than children in the other two groups . Children in the reassurance and control groups did not differ from each other in terms of behavioral distress . The present findings serve further to bolster the evidence for the efficacy of maternal distraction as a way to ameliorate child distress during invasive medical procedures Purpose To measure the difference in pain scores for newborns who were held and swaddled while undergoing routine heel lance procedures compared to newborns who were lying on their backs and not swaddled during heel lance . Additionally , we sought to compare the total amount of time it took to collect the specimens in each group . Design and Methods A total of 42 neonates recruited from a large tertiary hospital were enrolled in a r and omized controlled trial . Infants in the experimental group ( n = 22 ) were swaddled and held in an upright position during routine heel lance procedures while neonates in the control group ( n = 20 ) remained in a st and ard care position . Pain was measured with the Neonatal Inventory Pain Scale ( NIPS ) at two points in time for each group ( just before the heel lance procedure and at the completion of the heel lance ) . Total collection time was measured using a stopwatch accurate to 1/100th of a second . Specimen quality was measured based on the number of rejected specimens for each group . Descriptive statistics and t tests were used to analyze the data . Results The mean NIPS score for neonates who were swaddled and held during the procedure ( experimental group ) was significantly lower ( M = 1.3 , SD = .9 ) than the score for infants in the st and ard position ( control group ) ( M = 2.7 , SD = 1.3 ) , t ( 40 ) = -4.48 , p < .001 . Although the total collection time was lower for infants who were swaddled ( 2 minutes and 17 seconds , SD = 59 ) versus ( 2 minutes and 47 seconds , SD = 85 ) for controls , this was not a statistically significant difference ( p = .45 ) . Clinical Implication sSwaddling combined with positioning neonates upright during routine heel lance procedures offers nurses a nonpharmacologic method of neonatal pain reduction for heel sticks . This technique can be easily implemented on any unit independent of facility protocol s. Furthermore , the technique is not associated with any cost or policy development , making it more likely that nurses can use it in practice This study was design ed to investigate whether a brief intervention encouraging parental coping-promoting talk within the treatment room would have beneficial effects on infant pain responses to an immunization injection . Infant-parent dyads were recruited from a 6-month immunization clinic and r and omized to an intervention group ( n = 25 ) or st and ard care control group ( n = 25 ) . Parents in the intervention group received an information sheet describing adult verbalizations associated with better pain outcomes for infants . The immunization procedure was videotaped . Parents in the intervention condition made significantly more coping-promoting statements than parents in the control condition . Infants in the control condition cried significantly longer than infants in the intervention condition . Coping-promoting and distress-promoting statements did not differ in terms of affective quality . Infants whose parents had rated them as more difficult in temperament cried longer following the injection . Teaching parents to engage in coping-promoting behaviors within the infant treatment room is an effective , low-cost intervention Objective The purpose of this study was to examine the influence of prone and supine position in preterm infants during acute pain of blood collection . Setting Level III Neonatal Intensive Care Unit ( NICU ) . Study Design Thirty-eight preterm infants ( birthweight 1339 [ 590–2525 ] g , GA 29 [ 25– 32 ] wks ) were in 2 groups depending on their position in the isolette prior to and during heel lance at 32 weeks post-conceptional age . The study design was a comparison between groups ( Prone , Supine ) during 2 events ( Baseline , Heel lance ) . Outcome MeasurePain measures were multidimensional , including behavioral ( sleep – wake state and facial activity ) and physiological ( heart rate ) responses measured continuously prior to ( Baseline ) and during blood collection ( Lance ) . Results Both groups of infants displayed statistically significant shifts in sleep – wake state to greater arousal , and increased facial activity and heart rate , from Baseline to Lance . Prone position was associated with significantly more deep sleep during Baseline , compared with Supine position , but there were no differences in sleep-wake state during Lance . Minor increased facial activity was shown in some time segments of Baseline for infants in Supine compared with Prone , but did not differ overall between positions . Prone and Supine position did not affect heart rate significantly during Baseline or Lance events . Conclusions Prone position promotes deep sleep in preterm neonates at 32 weeks post-conceptional age when they are undisturbed . However , placement in prone position is not a sufficient environmental comfort intervention for painful invasive procedures such as heel lance for blood sampling in the NICU . Neonates require other environmental supports to promote coping with this stressful event Summary Background Many infants admitted to hospital undergo repeated invasive procedures . Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores . We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants . Methods In this double-blind , r and omised controlled trial , 59 newborn infants at University College Hospital ( London , UK ) were r and omly assigned to receive 0·5 mL 24 % sucrose solution or 0·5 mL sterile water 2 min before undergoing a clinical ly required heel lance . R and omisation was by a computer-generated r and omisation code , and research ers , clinicians , participants , and parents were masked to the identity of the solutions . The primary outcome was pain-specific brain activity evoked by one time-locked heel lance , recorded with electroencephalography and identified by principal component analysis . Secondary measures were baseline behavioural and physiological measures , observational pain scores ( PIPP ) , and spinal nociceptive reflex withdrawal activity . Data were analysed per protocol . This study is registered , number IS RCT N78390996 . Findings 29 infants were assigned to receive sucrose and 30 to sterilised water ; 20 and 24 infants , respectively , were included in the analysis of the primary outcome measure . Nociceptive brain activity after the noxious heel lance did not differ significantly between infants who received sucrose and those who received sterile water ( sucrose : mean 0·10 , 95 % CI 0·04–0·16 ; sterile water : mean 0·08 , 0·04–0·12 ; p=0·46 ) . No significant difference was recorded between the sucrose and sterile water groups in the magnitude or latency of the spinal nociceptive reflex withdrawal recorded from the biceps femoris of the stimulated leg . The PIPP score was significantly lower in infants given sucrose than in those given sterile water ( mean 5·8 , 95 % CI 3·7–7·8 vs 8·5 , 7·3–9·8 ; p=0·02 ) and significantly more infants had no change in facial expression after sucrose administration ( seven of 20 [ 35 % ] vs none of 24 ; p<0·0001 ) . Interpretation Our data suggest that oral sucrose does not significantly affect activity in neonatal brain or spinal cord nociceptive circuits , and therefore might not be an effective analgesic drug . The ability of sucrose to reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief . Funding Medical Research Council & NA ; Distraction has been shown to be an effective technique for managing pain in children ; however , few investigations have examined the utility of this technique with infants . The goal of the current study was to investigate the effectiveness of movie distraction in reducing infants ’ immunization distress . Participants were 136 infants ( range = 1–21 months ; M = 7.6 months , SD = 5.0 months ) and their parents , all of whom were recruited when presenting for routine vaccinations . The parent – child dyads were r and omly assigned to either a Distraction or Typical Care control condition . Infant and adult behaviors were assessed using a visual analog scale and a behavioral observation rating scale . Results indicated parents in the Distraction group engaged in higher rates of distraction than those in the Typical Care group , whereas there was no difference in the behavior of nurses in the Distraction and Typical Care groups . In addition , infants in the Distraction group displayed fewer distress behaviors than infants in the Typical Care group both prior to and during recovery from the injection . Findings suggest that a simple and practical distraction intervention can provide some distress relief to infants during routine injections PURPOSE To determine the effect of facilitated tucking ( FT ) on pain in preterm newborns during heel stick procedure done as a part of neonatal intensive care . METHODS This r and omized controlled cross-over pilot study included 20 preterm newborns of both sexes between gestational ages ( GA ) of 28 and 36 weeks based upon the eligibility criteria . Pain was measured using Premature Infant Pain Profile ( PIPP ) following both heel stick with FT and without FT . RESULTS The newborns had a lower PIPP score at 30 seconds ( Mean , SD : 8.80 , 3.82 ) , 60 seconds ( Mean , SD : 7.55 , 3.28 ) , 90 seconds ( Mean , SD : 7.25 , 3.06 ) and 120 seconds ( Mean , SD : 6.65 , 3.05 ) when heel stick was done with FT compared to the same procedure done without FT at 30 seconds ( Mean , SD : 11.20 , 3.44 ) , 60 seconds ( Mean , SD : 10.75 , 3.24 ) , 90 seconds ( Mean , SD : 10.60 , 3.22 ) and 120 seconds ( Mean , SD : 10.50 , 3.15 ) . A ( 2 X 4 ) factorial ANOVA showed a statistically significant difference between these two procedures in all the time periods viz . , 30 seconds ( p=0.044 ) , 60 seconds ( p=0.004 ) , 90 seconds ( p=0.002 ) and 120 seconds ( p < 0.0001 ) at 0.05 level in PIPP score and favoring FT . CONCLUSION FT is an effective non-pharmacological pain management in preterm newborns during routine neonatal intensive care Transanal one-stage endorectal pull-through ( TOSEPT ) has been presented as the most recent progression in treatment of Hirschsprung ’s disease ( HD ) , which may be able to replace various previous techniques . This prospect i ve study was design ed to compare the efficacy and probable complications of the commonly used open surgery with those of TOSEPT technique in management of HD . Forty-two children ( 35 boys and 7 girls ) between 3 days and 12 years of age underwent surgical treatment for HD — all after being diagnosed by barium enema over an 18-month period . In a manner of systematic r and om selection , 21 patients were operated by TOSEPT and the other 21 by Swenson procedures . All patients were followed-up at least for 12 months after hospital discharge . The necessary data containing age , sex , length of the resected aganglionic segment , intraoperative details , duration of hospital stay and postoperative functional results or complications were collected during hospitalization and follow-up period . There was no significant difference in age at the first operation , sex distribution and length of resected bowel between the two groups . Rate of postoperative complications were significantly higher in Swenson procedure group ( P < 0.01 ) . Narcotics were needed in all patients of Swenson procedure group but only in two patients operated by TOSEPT also required laparotomy ( P < 0.001 ) . The hospitalization period of TOSEPT group was also less than that of Swenson group ( P < 0.001 ) . The total cost of treatment by Swenson procedure is considerably higher than by TOSEPT . TOSEPT can significantly diminish postoperative pain , surgical complications , hospital stay and cost burden caused by Hirschsprung ’s disease . Besides , this procedure is cosmetically preferable because no visible scar remains Abstract Educating parents about ways to minimize pain during routine infant vaccine injections at the point of care may positively impact on pain management practice s. The objective of this cluster r and omized trial was to determine the impact of educating parents about pain in outpatient pediatric clinics on their use of pain treatments during routine infant vaccinations . Four hospital-based pediatric clinics were r and omized to intervention or control groups . Parents of 2- to 4-month-old infants attending the intervention clinics review ed a pamphlet and a video about vaccination pain management on the day of vaccination , whereas those in the control clinics did not . Parent use of specific pain treatments ( breastfeeding , sugar water , topical anesthetics , and /or holding of infants ) on the education day and at subsequent routine vaccinations 2 months later was the primary outcome . Altogether , 160 parent – infant dyads ( 80 per group ) participated between November 2012 and February 2014 ; follow-up data were available for 126 ( 79 % ) . Demographics did not differ between groups ( P > 0.05 ) . On the education day and at follow-up vaccinations , use of pain interventions during vaccinations was higher in the intervention group ( 80 % vs 26 % and 68 % vs 32 % , respectively ; P < 0.001 for both analyses ) . Educating parents about pain management in a hospital outpatient setting leads to higher use of pain interventions during routine infant vaccinations & NA ; This paper reports the development of a scale for assessing the quality of reports of r and omised controlled trials for psychological treatments . The Delphi method was used in which a panel of 15–12 experts generated statements relating to treatment and design components of trials . After three rounds , statements with high consensus agreement were review ed by a second expert panel and rewritten as a scale . Evidence to support the reliability and validity of the scale is reported . Three expert and five novice raters assessed sets of 31 and 25 published trials to establish scale reliability ( ICC ranges from 0.91 to 0.41 for experts and novices , respectively ) and item reliability ( Kappa and inter‐rater agreement ) . The total scale score discriminated between trials globally judged as good and poor by experts , and trial quality was shown to be a function of year of publication . Uses for the scale are suggested BACKGROUND Preterm infants ' repeated exposure to painful procedures may contribute to negative consequences . Thus , improving preterm infants ' neurodevelopmental outcomes requires prioritising their pain management . OBJECTIVES To compare the effectiveness of two non-pharmacological pain-relief strategies ( non-nutritive sucking and facilitated tucking ) with routine care on preterm infants ' pain , behavioural , and physiological responses before , during , and after heel-stick procedures . DESIGN Prospect i ve , r and omised controlled crossover trial . SETTING Level III Neonatal Intensive Care Unit in Taipei . METHOD Thirty-four preterm infants ( gestational age 29 - 37 weeks ) needing three procedural heel sticks were recruited by convenience sampling and r and omly assigned to a sequence of three treatments ( two pain-relief interventions and the control condition ) : ( 1 ) routine care , non-nutritive sucking , facilitated tucking , ( 2 ) non-nutritive sucking , facilitated tucking , routine care , and ( 3 ) facilitated tucking , routine care , non-nutritive sucking . Each treatment condition was performed on a different day to avoid any carry-over effect . Pain was measured by the Premature Infant Pain Profile ( PIPP ) , infant behaviour by a behavioural coding scheme , and physiological signals by electrocardiogram monitors . All data were collected 3 min without stimuli ( baseline ) , during heel-stick procedures , and recovery . RESULTS Infants receiving non-nutritive sucking and facilitated tucking had significantly lower mean ( st and ard deviation ) pain scores during heel-stick procedures ( 6.39 [ 3.35 ] and 7.15 [ 3.88 ] , respectively ) than those receiving routine care ( 9.52 [ 4.95 ] ) . Infants receiving non-nutritive sucking and facilitated tucking had significantly lower odds ratios ( 0.39 , p=0.011 and 0.34 , p=0.005 , respectively ) for pain ( PIPP score≥6 ) than infants receiving routine care after adjusting for time , baseline pain scores , and infants ' characteristics . Similarly , infants receiving non-nutritive sucking and facilitated tucking had significantly lower odds ratios ( 0.23 , p<0.001 and 0.28 , p=0.03 , respectively ) for moderate-to-severe pain ( PIPP score≥12 ) than infants receiving routine care . Infants receiving facilitated tucking had lower frequency ratios for stress-related behaviours , abnormal heart rates , and decreased oxygen saturation than infants receiving routine care . CONCLUSIONS Both non-nutritive sucking and facilitated tucking effectively reduced pain scores more than routine care during heel-stick procedures . Non-nutritive sucking reduced PIPP pain scores more effectively than facilitated tucking . However , facilitated tucking showed broader effects not only on relieving pain , but also on enhancing infants ' physiological and behavioural stability during heel-stick procedures Abstract Objectives : To assess and compare the analgesic effects of orally administered glucose and sucrose and pacifiers . To determine the synergistic analgesic effect of sucrose and pacifiers . Design : R and omised prospect i ve study with vali date d behavioural acute pain rating scale . Setting : Maternity ward . Participants : 150 term newborns undergoing venepuncture r and omly assigned to one of six treatment groups : no treatment ; placebo ( 2 ml sterile water ) ; 2 ml 30 % glucose ; 2 ml 30 % sucrose ; a pacifier ; and 2 ml 30 % sucrose followed by a pacifier . Results : Median ( interquartile ) pain scores during venepuncture were 7 ( 5 - 10 ) for no treatment ; 7 ( 6 - 10 ) for placebo ( sterile water ) ; 5 ( 3 - 7 ) for 30 % glucose ; 5 ( 2 - 8 ) for 30 % sucrose ; 2 ( 1 - 4 ) for pacifier ; and 1 ( 1 - 2 ) for 30 % sucrose plus pacifier . Mann-Whitney U test P values for comparisons of 30 % glucose , 30 % sucrose , pacifier , and 30 % sucrose plus pacifier versus placebo ( sterile water ) were 0.005 , 0.01 , < 0.0001 , and < 0.0001 , respectively . Differences between group median pain scores for these comparisons were 2 ( 95 % confidence interval 1 to 4 ) , 2 ( 0 to 4 ) , 5 ( 4 to 7 ) , and 6 ( 5 to 8) , respectively . P values for comparisons of 30 % glucose , 30 % sucrose , and 30 % sucrose plus pacifier versus pacifier were 0.0001 , 0.001 , and 0.06 , respectively . Differences between group medians for these comparisons were 3 ( 2 to 5 ) , 3 ( 1 to 5 ) , and 1 ( 0 to 2 ) , respectively . Conclusion : The analgesic effects of concentrated sucrose and glucose and pacifiers are clinical ly apparent in newborns , pacifiers being more effective than sweet solutions . The association of sucrose and pacifier showed a trend towards lower scores compared with pacifiers alone . These simple and safe interventions should be widely used for minor procedures in neonates . Key messages The analgesic effects on newborn infants of sucrose , glucose , and pacifiers can be clearly detected by a behavioural pain rating scale Pacifiers had a better analgesic effect than sweet solutions A synergistic effect was found with a combination of sucrose and pacifiers Sweet solutions and pacifiers constitute simple and safe interventions that can be used to provide analgesia in newborns during minor Objective . To test the effect of nonnutritive sucking ( NNS ) , music therapy ( MT ) , and combined NNS and MT ( NNS + MT ) , versus no intervention , on heart rate , transcutaneous oxygen ( TcPao 2 ) levels , and pain behavior of neonates in intensive care units having blood taken by a heel-stick procedure . Methodology . A within-subjects , counter-balancing , repeated- measures design conducted in a government-funded hospital in Hong Kong , comparing TcPao 2 levels , heart rate , and pain behavior outcomes in 27 neonates . Results . Repeated- measures multivariate analysis of variance revealed statistically significant differences in outcomes across all interventions ( Wilk 's λ = .142 ; F[3,27 ] = 31.82 ; η2 = .47 ) . One-way analysis of variance revealed that the 3 comfort interventions significantly reduced neonates ' heart rate ( Wilk 's λ = .647 ; F[2,27 ] = 18.93 ; η2 = .35 ) , improved their TcPao 2 levels ( Wilk 's λ = .481;F [ 2,27 ] = 37.42 ; η2 = .51 ) , and reduced their pain behavior ( Wilk 's λ = .312 ; F [ 2,27 ] = 76.42 ; η2 = .68 ) . Posthoc scheffe tests revealed that NNS + MT had the strongest effect on neonates ' TcPao 2 levels and pain behavior ; MT alone had the strongest effect on neonates ' heart rate . Conclusions . Health professionals using NNS + MT when doing heel-sticks can improve the TcPao 2 levels of neonates and reduce their pain . Using MT alone can improve the heart rate of neonates PURPOSE This study aims to assess the efficacy of Kangaroo Care ( KC ) on behavioral responses of term neonates to the pain of an intramuscular injection . DESIGN AND METHODS One hundred healthy term neonates were enrolled and r and omly assigned to intervention and control groups . In the intervention group , the neonate was held in KC for 10 min before the injection and remained in KC for the duration of the procedure . The primary outcome measure was the cumulative Neonatal Infant Pain Scale ( NIPS ) score immediately after injection . RESULTS The cumulative NIPS score immediately after injection in the intervention group was significantly lower ( p<.001 ) than in the control group . PRACTICE IMPLICATION S KC given before injection seems to effectively decrease pain and should be considered for minor invasive procedures in neonates OBJECTIVE To investigate , both objective ly and subjectively , the effect of music on children in a pediatric cardiac intensive care unit following heart surgery , in conjunction with st and ard care . METHODS R and omized clinical trial with placebo , assessing 84 children , aged 1 day to 16 years , during the first 24 hours of the postoperative period , given a 30 minute music therapy session with classical music and observed at the start and end of the session , recording heart rate , blood pressure , mean blood pressure , respiratory rate , temperature and oxygen saturation , plus a facial pain score . Statistical significance was set at 5 % . RESULTS Five of the initial 84 patients ( 5.9 % ) refused to participate . The most common type of heart disease was acyanotic congenital with left-right shunt ( 41 % of cases : 44.4 % of controls ) . Statistically significant differences were observed between the two groups after the intervention in the subjective facial pain scale and the objective parameters heart rate and respiratory rate ( p < 0.001 , p = 0.04 and p = 0.02 , respectively ) . CONCLUSIONS A beneficial effect from music was observed with children during the postoperative period of heart surgery , by means of certain vital signs ( heart rate and respiratory rate ) and in reduced pain ( facial pain scale ) . Nevertheless , there are gaps to be filled in this area , and studies in greater depth are needed Objectives . To determine whether skin-to-skin contact between mothers and their newborns will reduce the pain experienced by the infant during heel lance . Design . A prospect i ve , r and omized , controlled trial . Setting . Boston Medical Center , Boston , Massachusetts . Participants . A total of 30 newborn infants were studied . Interventions . Infants were assigned r and omly to either being held by their mothers in whole body , skin-to-skin contact or to no intervention ( swaddled in crib ) during a st and ard heel lance procedure . Outcome Measures . The effectiveness of the intervention was determined by comparing crying , grimacing , and heart rate differences between contact and control infants during and after blood collection . Results . Crying and grimacing were reduced by 82 % and 65 % , respectively , from control infant levels during the heel lance procedure . Heart rate also was reduced substantially by contact . Conclusion . Skin-to-skin contact is a remarkably potent intervention against the pain experienced during heel stick in newborns This was a feasibility pilot study to evaluate the efficacy of the nonpharmacologic pain management technique of gentle human touch ( GHT ) in reducing pain response to heel stick in premature infants in the neonatal intensive care unit ( NICU ) . Eleven premature infants ranging from 27 to 34 weeks ' gestational age , in a level III NICU in a teaching hospital , were recruited and r and omized to order of treatment in this repeated- measures crossover- design experiment . Containment with GHT during heel stick was compared with traditional nursery care ( side lying and " nested " in an incubator ) . Heart rate , respiratory rate , oxygen saturation , and cry were measured continuously beginning at baseline and continuing through heel warming , heel stick , and recovery following the heel stick . Infants who did not receive GHT had decreased respiration , increased heart rate , and increased cry time during the heel stick . In contrast , infants who received GHT did not have decreased respirations , elevated heart rates , or increased cry time during the heel stick . No significant differences were noted in oxygen saturation in either group . GHT is a simple nonpharmacologic therapy that can be used by nurses and families to reduce pain of heel stick in premature infants in the NICU Determinants of infant pain responses are important when assessing the efficacy of analgesics . In a r and omized controlled trial , 106 infants aged 2 to 6 months were positioned either supine ( SUP ) on the examination table or held ( HLD ) by a parent during routine immunization in a community pediatric office . There was no difference between the SUP and HLD infants in duration of crying , facial grimacing or visual analogue scale ( VAS ) pain scores . Similarly gender did not affect pain response . In contrast , 2-month-old infants displayed more pain during immunization than did 4 or 6-month-old infants Pain expression in the neonate ( NN ) is affected by intrinsic and extrinsic factors ( gestational and postconceptional age , states , and painful experiences ) . The impact of developmental care is discussed in relation to defined pain expression . The aim of this r and omized crossover study was to determine the impact of developmental care on pain expression during a nursing intervention in preterm NNs . Nineteen preterm NNs ( gestational age , 29 + /- 1.8 weeks body weight , 1212 + /- 255 g ) were included . Each NN experienced 2 r and omly ordered diaper changes ( with and without developmental support ) . Physiologic responses ( heart rate , oxygen saturation , hypoxic events with SaO(2 ) less than 80 % , bradycardia less than 80 beats/min ) were studied during 3 periods : baseline , diaper change ( time 0 ) , and recovery period . Pain expression was evaluated with 2 pain scales : chronic pain with Echelle Douleur et Inconfort ( [ EDIN ] or Pain and discomfort scale for newborns ) at time B60 minutes , 0 , + 30 minutes , and + 60 minutes and procedural pain with the Preterm Infant Pain Profile ( PIPP ) at time 0 . Statistical analysis was conducted with a Wilcoxon nonparametric test . PIPP , EDIN 0 , EDIN + 30 minutes , and EDIN + 60 minutes scores were significantly decreased with developmental care versus without developmental care : 8.7 + /- 1.9 v 11.1 + /- 2.36 ( P < .01 ) 0.6 + /- 0.5 v 3.2 + /- 2.9 ( P < .01);0.33 + /- 0.5 v 3.9 + /- 2.5 ( P < .001);0.3 + /- 3.4 v 3.4 + /- 3 ( P < .001 ) , respectively . Hypoxic events rate was decreased with developmental care during the baseline and diaper change periods . The lowest oxygen saturation observed during the PIPP measure was significantly higher with developmental care ( 88.8 % + /- 3 % v 81.8 % + /- 4 % P < .01 ) . Developmental care significantly decreased the PIPP and EDIN pain scores and hypoxic events during a routine nursing intervention Objective : To test if enhancing maternal skin-to-skin contact , or kangaroo mother care ( KMC ) by adding rocking , singing and sucking is more efficacious than simple KMC for procedural pain in preterm neonates . Study Design : Preterm neonates ( n=90 ) between 32 0/7 and 36 0/7 weeks ' gestational age participated in a single-blind r and omized crossover design . The infant was held in KMC with the addition of rocking , singing and sucking or the infant was held in KMC without additional stimulation . The Premature Infant Pain Profile was the primary outcome with time to recover as the secondary outcome . A repeated- measures analysis of covariance was employed for analyses . Result : There were no significant differences in any of the 30 s time periods over the 2 min of blood sampling nor in time to return to baseline . Compared to historical controls of the same age in incubator , the pain scores were lower and comparable to other studies of KMC . There were site differences related to lower scores with the use of sucrose in one site and higher scores in younger , sicker infants in another site . Conclusion : The sensorial stimulations from skin-to-skin contact that include tactile , olfactory sensations from the mother are sufficient to decrease pain response in premature neonates . Other studies showing that rocking , sucking and music were efficacious were independent of skin-to-skin contact , which , when used alone has been shown to be effective as reported across studies We assessed the effects of a familiar odor during routine blood draws in healthy preterm newborns . Infants were observed as they were undergoing either a capillary puncture on the heel ( heelstick ) or a venous puncture on the h and . During the procedure , one third of the infants were presented with an odor they had been familiarized with prior to the procedure , one third of the infants were presented with an odor , they had not been previously exposed to , and one third were presented with no odor . Heelsticks elicited more behavioral distress than venipunctures . Infants who were presented with a familiar odor during venipuncture showed no significant increase in crying and grimacing during the procedure compared to baseline levels . By comparison , infants presented with an unfamiliar odor or with no odor either during the heelstick or the venipuncture had a significant increase in crying and grimacing . When the pain was milder , i.e. , during a venipuncture , and a familiar odor was presented , infants showed little to no crying . These results are consistent with a body of evidence on early memory and olfactory competence in fetuses and newborns This study evaluates the impact of parent-provided distraction on children 's responses ( behavioral , physiological , parent , and self-report ) during an IV insertion . Participants were 542 children , 4 to 10 years old , r and omized to an experimental group that received a parent distraction coaching intervention or to routine care . Experimental group children had significantly less cortisol responsivity ( p = .026 ) . Children that received the highest level of distraction coaching had the lowest distress on behavioral , parent report , and cortisol measures . When parents provide a higher frequency and quality of distraction , children have lower distress responses on most measures Abstract Feeding and carrying have been interventions used by caregivers throughout history in relieving distress in infants . Recent studies on the food substance sucrose have eluci date d the comforting effect of the taste component of feeding while studies of rocking have examined the comforting effect of the vestibular component of carrying . The purpose of this study was to determine the effectiveness of sucrose and simulated rocking alone and in combination on diminishing pain response in preterm neonates undergoing routine heelstick procedure in the neonatal intensive care unit ( NICU ) . Preterm infants ( n=85 ) between 25–34 weeks post‐conceptual age ( PCA ) and 2–10 days post‐natal age ( PNA ) were r and omly assigned to one of four conditions for routine heelstick procedure . The conditions were ( 1 ) sucrose alone : 0.05 ml of 24 % sucrose was placed on the anterior surface of the tongue just prior to the lancing of the heel ; ( 2 ) simulated rocking alone : 15 min prior to and during the heelstick procedure , the infant was swaddled and put on an oscillating mattress ; ( 3 ) combination of sucrose and simulated rocking ; and ( 4 ) placebo : 0.05 ml sterile water administered just prior to heelstick . Physiological ( heart rate ) and behavioural ( facial actions ) responses from baseline across 90 s following heelstick were scored second‐to‐second . Facial actions were analysed with repeated measures MANCOVA and heart rate with repeated measures ANCOVA . Behavioural state and gestational age were covariates . The groups that received sucrose alone or in combination with simulated rocking showed less facial actions indicative of pain than the rocking alone or control group . The addition of rocking to the sucrose condition tended to further blunt the facial expression of pain , but this enhancement did not reach a significant level . Heart rate was not decreased by any intervention compared to the control condition . Although the simulated rocking did promote quiet sleep , which has been reported in earlier studies to blunt pain response , there was no difference between simulated rocking and control groups in either facial expressions indicative of pain or heart rate . The implication of these results is that sucrose , but not simulated rocking may be a means of diminishing pain from minor procedures in preterm infants . Further research is needed on the use of sucrose for more than one procedure as well as examining the contact component of natural rocking , as opposed to simulated rocking Background : Hospitalized infants are often exposed to many painful procedures as a result of their illness or disease process . Untreated or poorly treated pain can have deleterious effects on normal nociceptive pain development as well as future development of pain pathways . Mechanical vibration has been found to be efficacious in adult and pediatric population s for the relief of mild-to-moderate acute and chronic pain . However , little is known about the efficacy of this intervention in the neonatal population . Aim : The purpose of this study was to test the hypothesis that mechanical vibration would be efficacious in the relief of pain associated with heel sticks in neonates . Heel sticks are one of the most common painful procedures during neonatal hospitalization . Study Design : A r and om-sequencing crossover design was used with infants acting as their own controls . Subjects : Newborn infants of 35 weeks ’ gestation or greater ( N = 20 ) met the inclusion criteria for the study . Outcome Measures : Pain during heel stick was measured with the Neonatal Infant Pain Scale . The Neonatal Infant Pain Scale is a nonintrusive tool with extensive evidence of its reliability and validity in the neonatal population , when used by trained observers . Results : Mechanical vibration produced an analgesic effect for infants who had previously experienced painful heel sticks that approached statistical significance . Conclusions : The apparent limitations of mechanical vibration as analgesia may be due to the concurrent use of sucrose and pacifier , the effects of order ( ie , habituation ) , or type II error . Because vibration produced the predicted positive effect in some circumstances , further investigation in larger sample s within a r and omized clinical trial is warranted We investigated if nonnutritive sucking ( NNS ) during heelstick procedures alleviates behavioral distress in neonates . In our NICU , 26 neonates without severe complications ( mean Minde score 0.8 , range 0–3 ) , undergoing heelstick procedures at least twice a day , in the first 2 weeks of life , were enrolled in the trial ( mean gestational age 33.9 weeks , range 26–39 weeks , mean birth weight 1,988.5 g , range 1,200–4,010 g , mean Apgar score at the first minute 6.7 , range 4–10 , at the fifth minute 8.5 , range 6–10 ) . Two heelpricks were performed in each neonate with NNS r and omly assigned . Behavioral states , transcutaneous oxygen tension ( TcPO2 ) , heart rate , and respiratory rate were monitored before , during and after the heelstick procedures . Heelstick procedures lasted for a mean of 109 s ( range 50–230 s ) with NNS , and a mean of 128.8 s ( range 20–420 s ) without NNS . Compared with baseline , heart rate and behavioral distress increased and respiratory rate decreased during heelstick and after heelstick . Oxygen tension did not change . Nonnutritive sucking had no effect on respiratory rate or transcutaneous oxygen tension , but reduced the time of crying and the heart rate increase during the procedure . In conclusion , NNS can be recommended to reduce distress in newborns undergoing invasive routine procedures . Further studies are needed to evaluate the effects of NNS on respiratory rate and blood gas levels Objective The purpose of this study was to determine whether the viewing of cartoons in the acute care setting reduces the perception of pain by pediatric patients . Methods A convenience prospect i ve study of pediatric patients in pain was performed at a community teaching level I pediatric and adult emergency department , with 44,000 patient visits per year . The inclusion criteria for entry into the study were any child who presented to the emergency department in acute pain from any cause . The younger children were r and omized to watch a Barney cartoon in Spanish or English , and the older children were r and omized to view a Tarzan cartoon in Spanish or English . The younger children were assessed 5 minutes before the procedure , during the procedure , and 5 minutes after the procedure using Poker Chip Tool and Faces Scale . The older children were assessed at the same time interval using self-reporting and a visual analog scale . The study was internal review board approved . A difference of 20 % or greater was considered a significant difference . The data were analyzed using a general linear model-repeated measures a priori level of significance of P < 0.05 . Results There was a significant difference within subject effects : F1= 9.268 , significant at 0.03 , with observed power at 0.85 or 85 % , with the & agr ; set at 0.05 or less . A comparison of the groups revealed that there were no differences in the causes of pain ( F1 = 0.301 , P = 0.585 ) , pain duration ( F1 = 0.062 , P = 0.084 ) , or type of anesthesia , if used ( F1 = 0.064 , P = 0.804 ) between groups . This lack of difference was upheld for age ( F1 = 3.0407 , P = 0.068 ) , race ( F1 = 0.537 , P = 0.466 ) , and sex ( F1 = 0.002 , P = 0.964 ) . Conclusions The finding that cartoon viewing was effective does illustrate 1 more pain relief tool for use in the ED when pediatric patients present . It is useful because of the fact that it does not interfere with assessment of patients ’ presenting or underlying problems . The need for more ways in which to address pediatric pain persists BACKGROUND There is a need for a safe and effective non-pharmacological pain management method for preterm infants . The parents could be given an active role in the pain management which may help the parents to cope with the stress related to painful situations of the infant . AIMS To examine the effectiveness of a method called ' facilitated tucking by parents ' ( a parent holds the infant in a flexed position ) in pain management during endotracheal/pharyngeal suctioning of preterm infants . In addition , the parental perception of the method was studied . STUDY DESIGN A r and omized crossover trial . SUBJECTS Twenty preterm infants with one of their parents participated in the study . Infants ' gestational age ranged from 24 to 33 ( median 28 ) weeks and postnatal age from 6 to 37 days ( median 15 days ) . OUTCOME MEASURES The primary outcome was the Neonatal Infant Pain Scale ( NIPS ) score . Heart rate and oxygen saturation were recorded . Parents completed a question naire about their perception of the procedure . RESULTS The highest NIPS score was median 3 ( range from 2 to 6 ) using ' facilitated tucking by parents ' and median 5 ( range from 2 to 7 ) without tucking during suctioning ( p < 0.001 ) . The infants calmed down more quickly after ' facilitated tucking by parents ' ( 5 s vs. 17 s , p = 0.024 ) . Nineteen out of twenty parents preferred facilitated tucking during suctioning compared to control care . CONCLUSIONS Facilitated tucking by parents is an effective and safe pain management method during suctioning of preterm infants . This study shows that parents can be given an active role in the pain care of their preterm infants CONTEXT Newborns are subject to pain during routine invasive procedures . Pain caused by immunization injections is preventable , but remains untreated in neonates . OBJECTIVES The purpose of the study was to compare the effectiveness of three nonpharmacological pain relief strategies on newborns ' pain , physiological parameters , and cry duration before , during , and after hepatitis B intramuscular ( IM ) injection . METHODS In this prospect i ve , r and omized clinical trial , we enrolled 165 newborns ( gestational age , ≥36 weeks ) . The infants received IM injections and were r and omized to three treatment groups : nonnutritive sucking ( NNS ) , 20 % oral sucrose , or routine care . Pain was measured by the Neonatal Facial Coding System , physiological signals by electrocardiogram monitors , and cry duration using a stopwatch . RESULTS Pain was significantly lower among infants in the NNS ( B=-11.27 , P<0.001 ) and sucrose ( B=-11.75 , P<0.001 ) groups than that in controls after adjusting for time effects , infant sleep/wake state , number of prior painful experiences , and baseline pain scores . Infants in the NNS and sucrose groups also had significantly lower mean heart and respiratory rates than the controls . Cry duration of infants receiving sucrose was significantly shorter than those in the NNS ( Z=-3.36 , P<0.001 ) and control groups ( Z=-7.80 , P<0.001 ) . CONCLUSION NNS and oral sucrose can provide analgesic effects and need to be given before painful procedures as brief as a one-minute IM injection . Sucrose orally administered two minutes before injection more effectively reduced newborns ' pain during injection than NNS . Both nonpharmacological methods more effectively relieved newborns ' pain , stabilized physiological parameters , and shortened cry duration during IM hepatitis injection than routine care Objective : To determine the effects of a postural support protocol on the physiological and behavioral stability of preterm infants while undergoing a diaper change . Study Design : Forty-seven newborns having a birth weight ⩽2000 g and gestational age ⩽35 weeks were included in this r and omized , crossover clinical trial in a Neonatology Intensive Care Unit . The infants were observed as his or her own control and evaluated with and without the use of the proposed intervention , which was positioning the baby in a nest produced with rolled-up towels . During the observations , as control , the care model used by the unit was considered . Result : All babies displayed increased distress and pain scores during diaper changes . This was significantly less for babies nested compared with non-nested babies ( P<0.0001 ) . Conclusion : Diaper change is a distressing procedure for preterm infants . Providing postural support during diaper changes reduces the signs of distress and pain There are adverse physiologic effects of pain in neonates , and effective pain management must be an essential aspect of neonatal care . In this study we assessed the effect of a nonmaternal familiar scent on the neonatal pain responses . This study included 135 neonates r and omly assigned to one of three groups . During arterial puncture , one group was exposed to a vanillin scent on a gauze pad held next to their nose . They were familiarized with it the night before blood sampling by a scented gauze pad placed in the incubator next to their head for an average duration of 8.65 hours . The second group was not familiarized with the scent but was exposed to it during the procedure . The third group was neither familiarized nor exposed to the scent . The duration of crying in the familiar scent group was significantly lower than in the two other groups . Comparison of the physiologic parameters showed less variation in oxygen saturation level during arterial puncture in the familiar scent group . In this study , a familiar scent could reduce crying and oxygen consumption during arterial puncture Heart rate ( HR ) responses to the removal of a monitoring lead were assessed in 56 preterm infants who received moderate pressure , light pressure or no massage therapy . The infants who received moderate pressure massage therapy exhibited lower increases in HR suggesting an attenuated pain response . The heart rate of infants who received moderate pressure massage also returned to baseline faster than the heart rate of the other two groups , suggesting a faster recovery rate To underst and how the ' caregiving context ' could affect responses to procedural pain , the authors sought to determine whether ( 1 ) the combined effects of sweet taste and holding ( caregiving contact ) were greater than the effects of either alone , ( 2 ) any combined effects were additive or interactive , and ( 3 ) the interventions had similar effects on behavioral ( crying and facial activity ) and physiological ( heart rate , vagal tone ) responses to the heel-stick procedure in newborn infants in a r and omized two-factorial intervention trial . Eighty-five normally developing newborn infants were studied with a mean gestational age of 39.4 weeks on the 2nd or 3rd day of life . Infants were r and omized in blocks of eight to receive ( 1 ) no holding and water taste ( control participants ) , ( 2 ) no holding and sucrose taste ( sucrose group ) , ( 3 ) holding and water taste ( holding group ) , or ( 4 ) holding and sucrose taste ( holding and sucrose group ) . Crying was reduced significantly by taste and holding , and the interventions combined additively . Facial activity was only significantly reduced by holding . For physiological measures , the interventions interacted with each other and preintervention levels to reduce heart rate and lower vagal tone more during the procedure in infants in whom heart rate and vagal tone were higher before intervention . Consequently , sweet taste and holding interventions combined in complex ways when acting on different behavioral and physiological response systems to modify stressful pain experiences . The results suggest that providing a caregiving context when painful procedures are performed may be a simple and practical method of reducing pain experience in infants , and that no one measure captures these effects Many attempts have been made to obtain safe and effective analgesia in newborns . Oral glucose-water has been found to have analgesic properties in neonates . We investigated whether other sensory stimulation added to oral glucose provided more effective analgesia than oral glucose alone . In a r and omized prospect i ve double-blind trial , we studied 120 term newborns during heel prick . The babies were divided r and omly into six groups of 20 , and each group was treated with a different procedure during heel prick : A ) control;B ) 1 mL 33 % oral glucose given 2 min before the heel prick;C ) sucking;D ) 1 mL 33 % oral glucose plus sucking;E ) multisensory stimulation including 1 mL 33 % oral glucose ( sensorial saturation);F ) multisensory stimulation without oral glucose . Sensorial saturation consisted in massage , voice , eye contact , and perfume smelling during heel prick . Each heel prick was filmed and assigned a point score according to the Douleur Aiguë du Nouveau-né ( DAN ) neonatal acute pain scale . Camera recording began 30 s before the heel prick , so it was impossible for the scorers to distinguish procedure A ( control ) from B ( glucose given 2 min before ) , C ( sucking water ) from D ( sucking glucose ) , and E ( multisensory stimulation and glucose ) from F ( multisensory stimulation and water ) from the video . Procedure E ( multisensory stimulation and glucose ) was found to be the most effective procedure , and the analgesia was even more effective than that produced by procedure D ( sucking glucose ) . We conclude that sensorial saturation is an effective analgesic technique that potentiates the analgesic effect of oral sugar . It can be used for minor painful procedures on newborns Purpose : This study compared the efficacy of a behavioral pain reducing intervention ( facilitated tucking ) with st and ard neonatal intensive care unit ( NICU ) care for decreasing procedural pain ( endotracheal suctioning ) in very low birthweight ( VLBW ) infants . Study Design and Methods : A prospect i ve r and omized crossover design with infants as their own controls were used . The sample consisted of 40 VLBW infants , 23–32 weeks gestation , and weighing 560–1498 g with tracheal intubation . The infants were observed twice during each endotracheal suctioning experience ; one suctioning was done according to normal nursery routine ; another was done using facilitated tucking ( the caregiver “ h and -swaddling ” the infant by placing a h and on the infant ’s head and feet while providing flexion and containment ) . The Premature Infant Pain Profile ( PIPP ) measured the infant ’s pain response , and severity of illness of each infant was measured by the Score for Neonatal Acute Physiology ( SNAP ) and the NTISS ( Neonatal Therapeutic Intervention Scoring System ) . Repeated measures analysis of variance ( RMANOVA ) determined the efficacy of facilitated tucking for reducing procedural pain ( PIPP ) and the effects of order of intervention vs. control . Regression analyses examined the relationship of gestational age , severity of illness , and number of painful procedures to the pain response . Results : There was a significant difference between the PIPP scores for tucking and nontucking positions ( p = 0.001 ) and a nonsignificant interaction with order ( p = 0.64 ) as well as a nonsignificant main effect for order ( p = 0.46 ) . In the regression analyses , all predictors taken together did not significantly predict PIPP scores in the tucked position ( p = 0.11 ) or nontucked position ( p = 0.57 ) . Clinical Implication s : Facilitated tucking is a developmentally sensitive , nonpharmacological comfort measure that can relieve procedural pain in VLBW infants . Nurses need to be increasingly aware of infant pain during daily care taking , and to use vali date d pain assessment instruments . Further clinical research on individual pain assessment is needed for better underst and ing of the quality and significance of pain for each infant , and the factors that affect pain expression Observed 47 children ranging in age from 13 months to 7 years 9 months receiving injections as part of a regular visit to a pediatric clinic . Twenty-three children were r and omly assigned to a condition with parent ( mainly mothers ) present and 24 to a condition with parent absent . During the medical procedure , the child 's reactions were observed via videotape ( for later behavioral coding ) and physiological recording ( to measure heart rates ) . Following the injection , data were collected on the child 's preference of condition ( either parent present or parent absent ) for future injections . Older children ( but not younger ones ) showed significantly more behavioral distress when the parent was present . However , the oldest children 's preference of condition for future injections was overwhelmingly that of parent present ( 86 % ) Heel lancing is the most used method to obtain a blood sample in newborn and pre-term infants . The effectiveness on pain reduction of a new lancet , Tenderfoot was compared against the traditional Lancetta , r and omizing 40 preterm newborns to have the heel lanced with one of the two instruments and observing overall 76 blood sampling episodes . Newborns were observed at baseline , when disinfected , during and at the end of the blood sampling procedure . Statistically different behavioural responses to the pain of the puncture were observed during the blood sampling , in the ' recovery time ' after the procedure and in the number of pricks performed . When the Tenderfoot was used , less children cried during the first 5 seconds after the prick . The Tenderfoot is effective in reducing the heel prick pain , allows an easier collection of the blood , a reduction of the time necessary and of the need of squeezing the heel , therefore reducing the bruises and pain related to the squeezing itself . According to our data , its use is recommended for the obtainment of large quantities of blood , and in the severely ill newborns , that need frequent blood monitoring and several pricks . These characteristics render its use debatable because of the costs and of the bleeding for blood exams that require limited amount of blood ( blood glucose , blood gas analysis ) until its effects on the scarring time and outcome will be documented BACKGROUND Children with leukemia undergo painful procedures such as lumbar puncture and bone marrow aspiration . To overcome pain , certain units offer total anesthesia ; others offer generic support ; others offer no preparation at all . Since September , 1997 , we have provided leukemic children with art therapy ( AT ) , a nonverbal and creative modality that develops coping skills . Our goal is to prevent anxiety and fear during painful interventions as well as prolonged emotional distress . PROCEDURE We treated 32 children aged 2 - 14 years . The modes of AT before , during , and after the punctures were as follows : clinical dialogue to calm children and help them cope with painful procedures ; visual imagination to activate alternative thought processes and decrease the attention towards overwhelming reality and raise the peripheral sensitivity gate ; medical play to clarify illness , eliminate doubts , and offer control over threatening reality ; structured drawing to contain anxiety by offering a structured , predictable reality ( the drawing ) that was controllable by children ; free drawing to allow children to externalize confusion and fears ; and dramatization to help children accept and reconcile themselves to body changes . RESULTS Children hospitalized before September , 1997 , exhibited resistance and anxiety during and after painful procedures . By contrast , children provided with AT from the first hospitalization exhibited collaborative behavior . They or their parents asked for AT when the intervention had to be repeated . Parents declared themselves better able to manage the painful procedures when AT was offered . CONCLUSION AT was shown to be a useful intervention that can prevent permanent trauma and support children and parents during intrusive interventions PURPOSE To examine the efficacy of pacifiers and sugar , alone and in combination , for pain management in neonates . METHODS An experimental design examined pain responses of 84 newborns undergoing heelstick . They were r and omly assigned to one of four groups : ( a ) water-moistened pacifier , ( b ) sugar-coated pacifier , ( c ) 2 cc of a 12 % oral sucrose solution , or ( d ) control . Pain measures were duration of cry , vagal tone , and salivary cortisol . RESULTS Multivariate analysis of variance ( MANOVA ) revealed that the sugar-coated pacifier group cried significantly less than the water-moistened pacifier and control groups . Repeated measures analysis of variance ( ANOVA ) revealed that the sugar-coated pacifier group demonstrated significantly lower vagal tone during heelstick than the oral sucrose solution and control groups . This difference between the sugar-coated pacifier and control groups persevered for 15 minutes after heelstick . CONCLUSIONS Offering a sugar coated pacifier during heelstick in healthy neonates reduces pain behaviors more effectively than a water-moistened pacifier , 2 cc of a 12 % sucrose solution , or no intervention OBJECTIVE To identify the effectiveness of " facilitated tucking , " a nonpharmacologic nursing intervention , as a comfort measure in modulating preterm neonates ' physiologic and behavioral responses to minor pain . DESIGN Prospect i ve , repeated measure , r and om sequencing , and experimental . SETTING Level III neonatal intensive-care unit of a tertiary care university pediatric hospital . PARTICIPANTS Thirty preterm neonates , 25 - 35 weeks gestation . INTERVENTIONS Heart rate , oxygen saturation , and sleep state were recorded 12 minutes before , during , and 15 minutes after two heelsticks , one with and one without facilitated tucking . HYPOTHESIS Premature neonates will have less variation in heart rate and hemoglobin oxygen saturation , shorter crying and sleep disruption times , and less fluctuation in sleep states in response to the painful stimulus of a heelstick with facilitated tucking than without . RESULTS Neonates demonstrated a lower mean heart rate 6 - 10 minutes post-stick ( p < 0.04 ) , shorter mean crying time ( p < 0.001 ) , shorter mean sleep disruption time ( p < 0.001 ) , and fewer sleep-state changes ( p = 0.003 ) after heelstick with facilitated tucking than without . CONCLUSION Facilitated tucking is an effective comfort measure in attenuating premature neonates ' psychologic and behavioral responses to minor pain The purpose of this study was to evaluate the effects of a gentle human touch ( GHT ) intervention provided to 42 preterm infants ( 27 - 33 weeks gestational age ) , for 10 min , three times daily for 10 days . There was no significant difference in mean HR levels or in percent of abnormal heart rate ( HR ) or O2 saturation comparing 10-min baseline ( B ) , GHT , and 10-min post-touch ( PT ) phases . There were significantly lower levels of active sleep , motor activity , and behavioral distress during GHT compared to B and P phases . There were no differences among the 42 infants in the GHT group and 42 infants in a r and omly assigned control group on any outcome variable including weight gain , morbidity status , or behavioral organization . The findings suggest that GHT generally is a safe and soothing type of touch to provide to young preterm infants , but that individual infant responses to touch need to be continuously monitored by NICU staff and parents Pain in children is infrequently assessed and managed by nurses . One-on-one coaching based on audit with feedback and the use of opinion leaders have been effective in changing professional health care practice s. Coaching by an opinion leader for changing pediatric nurses ' pain practice s was tested in a clustered r and omized trial in six Canadian pediatric hospitals . The rate of pain assessment s , nurses ' knowledge , and nonpharmacological interventions increased in the coaching group . However , there were significant site differences that could not be attributed to the coaching but to factors inherent in the sites . The context in which interventions are implemented will influence the effectiveness of individualized interventions Background : Vaccination is one of the most common painful procedures in infants . The irreversible consequences due to pain experiences in infants are enormous . Breast feeding and massage therapy methods are the non-drug methods of pain relief . Therefore , this research aim ed to compare the vaccination-related pain in infants who underwent massage therapy or breast feeding during injection . Material s and Methods : This study is a r and omized clinical trial . Ninety-six infants were allocated r and omly and systematic ally to three groups ( breast feeding , massage , and control groups ) . The study population comprised all infants , accompanied by their mothers , referring to one of the health centers in Isfahan for vaccination of hepatitis B and DPT at 6 months of age and for MMR at 12 months of age . Data gathering was done using question naire and checklist [ neonatal infant pain scale ( NIPS ) ] . Data analysis was done using descriptive and inferential statistical methods with SPSS software . Results : Findings of the study showed that the three groups had no statistically significant difference in terms of demographic characteristics ( P > 0/05 ) . The mean pain scores in the breast feeding group , massage therapy , and control group were 3.4 , 3.9 , and 4.8 , respectively ( P < 0.05 ) . Then the least significant difference ( LSD ) post hoc test was performed . Differences between the groups , i.e. massage therapy and breast feeding ( P = 0.041 ) , breast feeding group and control ( P < 0.001 ) , and massage therapy and control groups ( P = 0.002 ) were statistically significant . Conclusion : Considering the results of the study , it seems that breast feeding during vaccination has more analgesic effect than massage therapy . Therefore , it is suggested as a noninvasive , safe , and accessible method without any side effects for reducing vaccination-related pain AIM This article is a report of a r and omized controlled trial of the effects of ' M ' technique massage with or without m and arin oil compared to st and ard postoperative care on infants ' levels of pain and distress , heart rate and mean arterial pressure after major craniofacial surgery . BACKGROUND There is a growing interest in non-pharmacological interventions such as aromatherapy massage in hospitalized children to relieve pain and distress but well performed studies are lacking . METHODS This r and omized controlled trial allocated 60 children aged 3 - 36 months after craniofacial surgery from January 2008 to August 2009 to one of three conditions ; ' M ' technique massage with carrier oil , ' M ' technique massage with m and arin oil or st and ard postoperative care . Primary outcome measures were changes in COMFORT behaviour scores , Numeric Rating Scale pain and Numeric Rating Scale distress scores assessed from videotape by an observer blinded for the condition . RESULTS In all three groups , the mean postintervention COMFORT behaviour scores were higher than the baseline scores , but differences were not statistically significant . Heart rate and mean arterial pressure showed a statistically significant change across the three assessment periods in all three groups . These changes were not related with the intervention . CONCLUSIONS Results do not support a benefit of ' M ' technique massage with or without m and arin oil in these young postoperative patients . Several reasons may account for this : massage given too soon after general anaesthesia , young patients ' fear of strangers touching them , patients not used to massage AimS ensorial saturation ( SS ) is a procedure in which touch , massage , taste , voice , smell , and sight compete with pain , producing almost complete analgesia during heel prick in neonates . SS is an apparently complex maneuvre , but when correctly explained it is easily learnt . In the present paper , we studied its feasibility , assessing whether a long training is really needed to achieve good results . Material s and Methods We enrolled 66 consecutive babies and divided them r and omly into 3 groups which received the following forms of analgesia : glucose plus sucking ( A ) , SS performed by nurses ( B ) , SS performed by mothers ( C ) . We did not use perfume on the caregivers ' h and s , so that babies could smell the natural scent of the h and s. We assessed pain level by the ABC scale . Results Median scores of groups A , B , and C were : 1 ( 0 to 6 ) , 0 ( 0 to 4 ) , and 0 ( 0 to 6 ) , respectively . Mean scores were : 0.6 , 0.6 , and 1.7 and st and ard errors were 0.38 , 0.22 , and 0.32 , respectively . Scores of groups B and C were significantly lower than that of A ( P=0.03 and 0.006 , respectively ) . No significant difference was found between values of scores of groups B and C. Conclusions Even without the use of perfume on the h and s , SS was effective as an analgesic maneuvre . It made no difference whether SS was performed by mothers who applied it for the first time or experienced nurses . SS is rapid to learn and any caregiver ( mother , pediatrician or nurse ) can effectively use it INTRODUCTION Previous work has shown that parents prefer to be present when their children undergo common invasive procedures , although physicians are ambivalent about parental presence . PURPOSE To determine the effect of a parent-focused intervention on the pain and performance of the procedure , anxiety of parents and clinicians , and parental satisfaction with care . POPULATION Children younger than 3 years old undergoing venipuncture , intravenous cannulation , or uretheral catheterization . SETTING Pediatric emergency department of Boston City Hospital . DESIGN R and omized controlled trial with three groups ; parents present and given instructions on how to help their children ; parents present , but no instructions given ; and parents not present . INTERVENTION The parents were instructed to touch , talk to , and maintain eye contact during the procedure . RESULTS A total of 431 parents was r and omized to the intervention ( N = 153 ) , present ( N = 147 ) , and not present ( N = 131 ) groups . The groups were equivalent with respect to measured sociodemographic variables and parents ' previous experience in the pediatric emergency department . No differences emerged with respect to pain ( 3-point scale measured by parent and clinician , and analysis of cry ) ; performance of the procedure ( number of attempts , completion of procedure by first clinician , time ) ; clinician anxiety ; or parental satisfaction with care . Parents who were present were more likely to rate the pain of the children as extreme/severe ( 52 % ) in comparison to clinicians ( 15 % , kappa .07 , poor agreement ) and were significantly less anxious than parents who were not present . CONCLUSION Overall , the intervention was not effective in reducing the pain of routine procedures . Parental presence did not negatively affect performance of the procedure or increase clinician anxiety . Parents who were present were less anxious than those who were not present . CLINICAL IMPLICATION In general , parents have indicated that they want to be present when their children undergo procedures . The results of this study challenge the traditional belief that parental presence negatively affects our ability to successfully complete procedures . We should encourage parents who want to be present to stay during procedures OBJECTIVE To assess the effectiveness of sucrose as an analgesic agent during routine immunization injections for infants ( age range , 2 weeks to 18 months ) . STUDY DESIGN Double-blind , r and omized control trial . SETTING Ambulatory care clinic of a large tertiary care center . PARTICIPANTS A consecutive sample of 285 infants were r and omly assigned to one of three treatment groups . INTERVENTION Subjects received either no intervention or drank 2 mL of sterile water or 2 mL or a 12 % sucrose solution 2 minutes before administration of the immunization . MAIN OUTCOME MEASURE Infants were videotaped during immunization for later interval recording of pain-induced vocalizations . RESULTS Results were analyzed by using two-way repeated measure analyses of variance . Two-week-old infants who received either the sterile water or sucrose solution cried significantly less than infants who received no intervention ( F=5.92,P<.005 ) . For older infants , those who received water or sucrose cried significantly less only if they were administered one injection rather than two injections ( F=3.36,P<.05 ) . CONCLUSIONS We found that when infants drank sucrose or sterile water , significantly fewer pain vocalizations were produced , but only for 2-week-old infants . For older infants , differences were found only when the number of injections was included in the analysis . We exp and on previous findings by demonstrating that both the age of the child and the number of painful exposures can attenuate calming effects . In addition , the results suggest that in the absence of nonnutritive sucking , the actual analgesic effects of sucrose may be nonspecific . Further study is needed of the possible analgesic effects of sucrose PURPOSE To verify the nutritive and non-nutritive stimuli efficacy in the newborn 's response to pain during venipuncture . METHODS The main sample was composed of 64 newborns that were r and omly divided into three groups . The first group ( n=20 ) received nutritive sucking stimulus that was performed through maternal breastfeeding . The second group ( n=21 ) received non-nutritive sucking stimulus that was performed through the introduction of the research er little finger in the newborn 's oral cavity . The third group or control group ( n=23 ) did not receive any analgesia stimulus . The newborns were evaluated using the Neonatal Infant Pain Scale , and the responses to painful stimuli were compared . RESULTS The nutritive as well as non-nutritive suction methods provided a comforting effect , result ing in lower pain response scores ( p<0.05 ) . There was no difference between the analgesia provided by both methods ( p>0.05 ) . CONCLUSION The nutritive and the non-nutritive sucking stimuli proved to be efficacious tools in relieving pain among newborns We evaluated the differences in histological and immunological findings in children with recurrent tonsillitis and tonsillar hyperplasia and assessed the risk for relapsing tonsillar hyperplasia or recurrent tonsillitis after tonsillotomy in a prospect i ve clinical study . Sixty-four children with recurrent tonsillitis underwent traditional ( total ) blunt dissection tonsillectomy between October 2003 and July 2004 . Partial tonsillectomy ( tonsillotomy ) using CO2-laser technique was performed on 49 children with tonsillar hyperplasia and no history of recurrent tonsillitis between August 2003 and March 2005 . The present study compares preoperative serum anti-streptolysin-O antibody and immunoglobulin levels ( IgG , IgA and IgM ) , C-reactive protein levels ( CRP ) and blood leukocyte counts of the two study groups . Additionally the tonsillar tissue removed by tonsillotomy or tonsillectomy was histologically examined in order to determine the grade of hyperplasia , chronic inflammation and fibrosis . Furthermore , the grade of fresh inflammation within the tonsillar crypts of the specimens was analysed . The parents of 40 patients treated by laser tonsillotomy were surveyed in average 16 months . There was no statistically significant difference in preoperative serum anti-streptolysin-O antibody and immunoglobulin levels , C-reactive protein levels and blood leukocyte counts between the two study groups . All specimens showed the histological picture of hyperplasia . There was no statistically significant difference in the grade s of hyperplasia between the two study groups . Signs of fresh but mild inflammation within the tonsillar crypts could be found in over 70 % of both study groups . Fibrosis only occurred in children with recurrent tonsillitis ( 9 % ) . In all specimens signs of chronic inflammation could be detected . The histological examinations of specimens from children with repeated throat infections more frequently showed a moderate chronic inflammation of the tonsillar tissue . Two of forty patients treated by tonsillotomy required a subsequent tonsillectomy due to a recurrence of tonsillar hyperplasia but no recurrent tonsillitis occurred . Tonsillotomy with CO2-laser technique is an effective surgical procedure with a long-lasting effect in patients with tonsillar hyperplasia . The benefits over conventional tonsillectomy are a lower risk for postoperative haemorrhage , reduced postoperative morbidity and accelerated recovery . Even in children with no history of recurrent tonsillitis signs of chronic inflammation histologically can be found in specimens after tonsillotomy . The occurrence of recurrent tonsillitis after tonsillotomy is rare , however . A low incidence of relapsing tonsillar hyperplasia after tonsillotomy should be expected . Preoperative laboratory investigations show few differences in patients with tonsillar hyperplasia and recurrent tonsillitis . Components of the antimicrobial defense system are also produced by chronically infected tonsils . Therefore tonsillotomy with CO2-laser could also be an option in some patients with mild symptoms of recurrent tonsillitis The aim of this study was to examine whether children experience less fear , distress and pain connected to a routine needle insertion in an intravenous port when subjected to an intervention : blowing soap bubbles or having a heated pillow vs. st and ard care . Twenty-eight children , 2 - 7 years , cared for at a paediatric oncology unit , undergoing a routine needle insertion in an intravenous port were included consecutively . All children were subjected to two needle insertions ; at the first they received st and ard care , and at the second st and ard care + a r and omized intervention . Parents and nurses assessed children 's fear , distress and pain on 0 - 100 mm visual analogue scales . According to parents ' report , children experienced less fear when subjected to intervention vs. st and ard care reported by parents ( P < 0.001 ) . Children also experienced less fear ( P < 0.05 ) and distress ( P < 0.05 ) when subjected to st and ard care + blowing soap bubbles vs. st and ard care ( n = 14 ) , and less fear when subjected to st and ard care + heated pillow vs. st and ard care ( P < 0.05 ) . Nurses ' reports did not show any differences for st and ard care + intervention vs. st and ard care . Blowing soap bubbles or having a heated pillow is more effective than st and ard care in reducing children 's fear and distress in needle procedures , according to parents ' report BACKGROUND In Switzerl and approximately 8 % of infants are born prematurely . Some of them undergo mechanical ventilation including endotracheal suctioning ( ETS ) . ETS is one of the most frequently performed interventions and is linked to stress and pain , but its treatment is controversial . In Switzerl and there is a lack of st and ardisation in pain relief for ETS . AIMS To test the hypothesis that an intermittent dose of morphine reduces pain during ETS and that subsequent multisensorial stimulation ( MSS ) , as a non pharmacological comforting intervention , helps infants to recover from experienced pain . METHOD A r and omized placebo controlled trial in two tertiary neonatal intensive care units ( NICU ) with a sample of 30 mechanically ventilated preterm infants was conducted . Pain was measured by three pain assessment tools ( Bernese Pain Scale for Neonates , Premature Infant Pain Profile and Visual Analogue Scale ) RESULTS Morphine did not lead to any pain relief from ETS as measured by three pain scales . Nor did the comforting intervention of MSS show any effect . Repeated-measure analysis of variance for the within and between groups comparison showed no statistical significance . CONCLUSIONS The administration of morphine for pain relief in ventilated preterm neonates during ETS remains question able and the use of MSS as a comforting intervention after painful stimulus can not be recommended . The validity testing of the instruments for this patient population should undergo a systematic validation trajectory . Future research should focus on options among non pharmacological interventions for relieving pain during ETS UNLABELLED The aim of this r and omized crossover study was to evaluate the impact of environmental and behavioral interventions ( EBI ) on behavioral , physiologic , and biologic stress response during a weighing procedure in neonates . Three groups of 15 neonates included ( A ) gestational age ( GA ) , < or = 32 weeks ; ( B ) GA , 32 weeks , 1 day to 36 weeks , 6 days ; and ( C ) GA , > or = 37 weeks . Each neonate experienced 2 weighing procedures with and without EBI . Pain was evaluated by using the Neonatal Infant Pain Scale ( NIPS ) and the Neonatal Pain and Discomfort Scale ( EDIN ) . Heart rate and oxygen saturation were recorded . Salivary sample s were obtained for cortisol assay . Cerebral tissue oxygenation index ( TOI ) was recorded with near-infrared spectroscopy . A significant decrease of NIPS and EDIN was observed with EBI versus control . Mean heart rate was lower with EBI . No difference in cortisol level changes was observed . For groups A and B , a trend of increased TOI was observed with EBI . We concluded that EBI during a nursing procedure provides a decrease in pain scores in preterm and term neonates with changes in heart rate . PERSPECTIVE This study evaluates the impact of combined environmental and behavioral interventions on pain responses in neonates during a weighing procedure . The results indicate a decrease in behavioral pain scores and in heart rate for preterm and term neonates and a trend in increased brain oxygenation depending on gestational age BACKGROUND Acute pain is a significant stressor for preterm infants in neonatal intensive care units ( NICU ) ; however , little is known about the effects of acute pain on subsequent motor responses during clusters of tactile h and ling . AIMS ( 1 ) To compare facial , body and heart rate reactivity in preterm infants at 32 weeks gestational age ( GA ) during routine care-giving tasks following a rest period ( RCC : diapering , measuring abdominal girth and axillary temperature , mouth care ) with their responses to Clustered Care following blood collection ( PCC ) . ( 2 ) To examine how GA at birth affects patterns of stress and self-regulatory behaviors during RCC and PCC . STUDY DESIGN Within-group crossover design ( r and om order ) . SUBJECTS Preterm infants , N=54 ( mean GA at birth 29.3 + /- 2.2 weeks ; mean birth weight 1257 + /- 423 g ) were assessed at 32 weeks GA in the NICU . OUTCOME MEASURES The Newborn Developmental Care and Assessment Program ( NIDCAP ) and Neonatal Facial Coding System ( NFCS ) were coded from continuous bedside video recordings . Changes in mean heart rate ( HR ) were computed using custom physiologic software . RESULTS All infants had heightened facial , body and HR responses when CC followed a painful procedure compared to when they had not been h and led prior to CC . Infants born at earlier GA ( < 30 weeks ) had equal numbers of stress cues during RCC and PCC , but dampened self-regulatory behaviors during PCC . CONCLUSION Prior pain induces heightened biobehavioral reactivity in preterm infants during subsequent tactile procedures . In addition , clustering care is particularly stressful for infants born at earlier GA BACKGROUND Preliminary studies suggested that pain experienced by infants in the neonatal period may have long-lasting effects on future infant behaviour . The objectives of this study were to find out whether neonatal circumcision altered pain response at 4-month or 6-month vaccination compared with the response in uncircumcised infants , and whether pretreatment of circumcision pain with lidocaine-prilocaine cream ( Emla ) affects the subsequent vaccination response . METHODS We used a prospect i ve cohort design to study 87 infants . The infants formed three groups -- uncircumcised infants , and infants who had been r and omly assigned Emla or placebo in a previous clinical trial to assess the efficacy of Emla cream as pretreatment for pain in neonatal circumcision . Infants were videotaped during vaccination done at the primary care physician 's clinic . Videotapes were scored without knowledge of circumcision or treatment status by a research assistant who had been trained to measure infant facial action , cry duration , and visual analogue scale pain scores . FINDINGS Birth characteristics and infant characteristics at the time of vaccination , including age and temperament scores , did not differ significantly among groups . Multivariate ANOVA revealed a significant group effect ( p < 0.001 ) in difference ( vaccination minus baseline ) values for percentage facial action , percentage cry time , and visual analogue scale pain scores . Univariate ANOVAs were significant for all outcome measures ( p < 0.05 ) : infants circumcised with placebo had higher difference scores than uncircumcised infants for percentage facial action ( 136.9 vs 77.5 % ) , percentage cry duration ( 53.8 vs 24.7 % ) , and visual analogue scale pain scores ( 5.1 vs 3.1 cm ) . There was a significant linear trend on all outcome measures , showing increasing pain scores from uncircumcised infants , to those circumcised with Emla , to those circumcised with placebo . INTERPRETATION Circumcised infants showed a stronger pain response to subsequent routine vaccination than uncircumcised infants . Among the circumcised group , preoperative treatment with Emla attenuated the pain response to vaccination . We recommend treatment to prevent neonatal circumcision pain The purpose of this study was to examine the effects of therapeutic play on outcomes of children undergoing day surgery . Two hundred and three children admitted for day surgery were invited to participate in a r and omized controlled trial . The experimental group received therapeutic play ; the control group received routine information preparation . Children in the experimental group reported significantly lower state anxiety scores in pre- and postoperative periods and exhibited fewer negative emotions at induction of anesthesia than children in the control group . No significant differences were found between the two groups in postoperative pain . The study provides some evidence that therapeutic play is effective in pre- as opposed to postsurgical management of children Fifty children were involved in a r and omized , controlled trial to evaluate the effectiveness of either osteopathic manipulation or acupuncture as a 6-month therapeutic adjunct for children with spastic cerebral palsy . Exit interviews were used to obtain parental perceptions and form the basis of this report . Only 2 of 17 parents reported positive gains while their child was in a wait-list control period but all 17 reported gains while in the treatment phase of the study . Ninety-six percent ( 48 of 50 ) of the parents reported some improvement while their child was receiving treatments but the gains varied from child to child . The most frequent gains were seen in improvement in the use of arms or legs ( 61 % and 68 % ) and more restful sleep ( 39 % and 68 % ) in the osteopathic and the acupuncture groups , respectively . Improvement in mood and improved bowel function were also very common benefits noted by the parents in both groups Abstract Objectives : To investigate whether breast feeding is effective for pain relief during venepuncture in term neonates and compare any effect with that of oral glucose combined with a pacifier . Design : R and omised controlled trial . Participants : 180 term newborn infants undergoing venepuncture ; 45 in each group . Interventions : During venepuncture infants were either breast fed ( group 1 ) , held in their mother 's arms without breast feeding ( group 2 ) , given 1 ml of sterile water as placebo ( group 3 ) , or given 1 ml of 30 % glucose followed by pacifier ( group 4 ) . Video recordings of the procedure were assessed by two observers blinded to the purpose of the study . Main outcome measures : Pain related behaviours evaluated with two acute pain rating scales : the Douleur Aiguë Nouveau-né scale ( range 0 to 10 ) and the premature infant pain profile scale ( range 0 to 18 ) . Results : Median pain scores ( interquartile range ) for breast feeding , held in mother 's arms , placebo , and 30 % glucose plus pacifier groups were 1 ( 0–3 ) , 10 ( 8.5 - 10 ) , 10 ( 7.5 - 10 ) , and 3 ( 0–5 ) with the Douleur Aiguë Nouveau-né scale and 4.5 ( 2.25 - 8 ) , 13 ( 10.5 - 15 ) , 12 ( 9–13 ) , and 4 ( 1–6 ) with the premature infant pain profile scale . Analysis of variance showed significantly different median pain scores ( P<0.0001 ) among the groups . There were significant reductions in both scores for the breast feeding and glucose plus pacifier groups compared with the other two groups ( P<0.0001 , two tailed Mann-Whitney U tests between groups ) . The difference in Douleur Aiguë Nouveau-né scores between breast feeding and glucose plus pacifier groups was not significant ( P=0.16 ) . Conclusions : Breast feeding effectively reduces response to pain during minor invasive procedure in term neonates . What is already known on this topic Current pharmacological treatments are not appropriate for pain relief during minor procedures like venepuncture or heel prick in newborn infants Oral sweet solutions , non-nutritive sucking , and skin to skin contact reduce procedural pain in newborn infants What this study adds Breast feeding during a painful procedure effectively reduces the response to pain in newborn infants The analgesic properties of breast feeding are at least as potent as the combination of sweet solutions and a OBJECTIVE To assess the effectiveness of simple behavioral interventions at immunization on behavioral and biochemical indicators of distress in infants and parents in a primary care setting . DESIGN Subjects were enrolled sequentially to control ( st and ard care ) and intervention groups . Intervention parents ( n=57 ) were provided information about techniques to help their infants at immunization . St and ard care parents ( n=45 ) did not receive this information . Immunizations were videotaped and coded for infant and parent behaviors . Using a visual analog scale , parents rated their infant 's and their own comfort at study enrollment , immediately after immunization , and at check-out . Saliva sample s collected from infants and parents at study enrollment and at 15 , 30 , and 60 minutes after immunization were assayed for cortisol concentration by st and ard radioimmunoassay . Data were analyzed using chi2 , analysis of variance , and general linear modeling . Patterns of salivary cortisol change after immunization were analyzed using hierarchical linear modeling . SETTING A single , urban pediatric practice during 2 summers ( 1997 and 1998 ) . SUBJECTS Infants 2 to 24 months of age ( n= 102 ) and their parents . MAIN OUTCOME MEASURES Duration of infant distress ( in seconds ) ; parent use of behavioral intervention ; infant and parent salivary cortisol concentrations ( in nanomoles per liter ) . RESULTS Intervention parents were more likely to use a behavioral technique with their infants before immunization ( P<.05 ) . Total infant distress was shorter for intervention infants at immunization ( P<.01 ) , and these infants were rated as more comfortable by their parents ( P<.001 ) immediately after immunization . Salivary cortisol levels were lower for intervention infants at 15 , 30 , and 60 minutes after immunization ( P<.05 ) . CONCLUSION Simple behavioral interventions before immunization are associated with reductions in behavioral and biochemical indicators of infant distress Crying commonly occurs in response to heel stick and adversely affects the infant 's physiologic stability . Minimal crying in response to pain is desired . " Kangaroo Care , " skin contact between mother and infant , reduces pain and may reduce crying in response to pain . The purpose of this pilot study was to test Kangaroo Care 's effect on the preterm infant 's audible and inaudible crying response to heel stick . Inaudible crying has not been previously studied . A prospect i ve r and omized cross-over study with 10 preterm infants 2 - 9 days old ( 30 - 32 weeks ' postmenstrual age ) was conducted . Infants were r and omly assigned to two sequences ( sequence A : day 1 heel stick in Kangaroo Care [ after 30 min of prone skin contact upright between maternal breasts ] and day 2 heel stick in incubator [ inclined , nested and prone ] ; or sequence B : opposite of sequence A ) was conducted . Videotapes of baseline , heel warming , heel stick , and recovery phases were scored for audible and inaudible crying times . Audible and inaudible crying times for each subject in each phase were summed and analyzed by repeated- measures analysis of variance . Subject characteristics did not differ between those in the two sequences . Crying time differed between the study phases on both days ( p < or= .001 ) . When in Kangaroo Care compared with the incubator , crying time was less during the heel stick ( p = .001 ) and recovery ( p = .01 ) phases , regardless of sequence . Because Kangaroo Care reduced crying in response to heel stick in medically stable preterm infants , a definitive study is merited before making recommendations OBJECTIVE To assess the effect of Eutectic Mixture of Local Anaesthetics cream and rattle on soothing the vaccination pain on four-month-infants . METHODS The single blind r and omised clinical trial was conducted from May 2012 to February 2013 at a clinic under the Gonabad University of Medical Sciences , Iran , and comprised four-month infants who were selected r and omly and divided into three groups . In one group , 2 g of eutectic mixture of local anaesthetics cream was rubbed on the injection spot before administration ; for the other group , the rattle was shaken from 30s to 15s before injection . The last group consisted of controls . The infants were filmed after vaccination . Afterward , a pain question naire was filled out by a trained observer . SPSS 11.5 was used for statistical analysis . RESULTS Of the 50 subjects in the study 16 ( 32 % ) each were in the cream and rattle groups , while the rest ( 36 % ) were in the control group . The severity of the pain before intervention in the control , cream and rattle groups was 2.22 + /- 0.88 , 2.12 + /- 0.95 and 2.25 + /- 1.06 respectively , which were not statistically significant ( p < 0.93 ) . Likewise , the mean severity of pain at the moment of intervention in the three above groups were 8.67 + /- 0.77 , 7.12 + /- 0.5 and 7.87 + /- 0.96 respectively , which was significantly different ( p < 0.001 ) . The severity of pain 15seconds after the intervention in the groups was 5.06 + /- 1.51 , 4.87 + /- 1.31 and 4.19 + /- 1.94 respectively , which were not statistically different ( p < 0.27 ) . CONCLUSION The eutectic mixture of local anaesthetics cream and shaking rattle were effective in attenuating pain of vaccination among the infants , but the latter was not as significant as the former Young children are generally restrained in supine position for IV starts , a position that creates fear but is presumed necessary . This study r and omly assigned children of ages 9 months to 4 years ( N = 118 ) to being held upright by a parent or lying flat on an exam table for their IV procedure . Distress scores as rated by the Procedure Behavior Rating Scale were significantly lower in the upright positioning group ( p = .000 ) ; parents were more satisfied with the upright position , and the upright position did not significantly alter the number of IV attempts needed . The upright position appears to be an effective way to decrease IV distress in young children Abstract Nonpharmacological interventions are important alternatives for pain relief during minor procedures in preterm neonates . Skin‐to‐skin contact or kangaroo mother care is a human and efficient way of caring for low‐weight preterm neonates . The aim of the present study was to assess the analgesic effect of kangaroo care compared to oral glucose on the response of healthy preterm neonates to a low‐intensity acute painful stimulus . Ninety‐five preterm neonates with a postmenstrual age of 28–36 weeks were r and omly assigned to three groups in a single‐blind manner . In group 1 ( isolette , n = 33 ) , the neonate was in the prone position in the isolette during heel lancing and did not receive analgesia . In group 2 ( kangaroo method , n = 31 ) , the neonate was held in skin‐to‐skin contact for 10 min before and during the heel‐lancing procedure . In group 3 ( glucose , n = 31 ) , the neonate was in the prone position in the isolette and received oral glucose ( 1 ml , 25 % ) 2 min before heel lancing . A smaller variation in heart rate ( p = 0.0001 ) and oxygen saturation ( p = 0.0012 ) , a shorter duration of facial activity ( brow bulge , eye squeeze and nasolabial furrowing ) ( p = 0.0001 ) , and a lower PIPP ( Premature Infant Pain Profile ) score ( p = 0.0001 ) were observed in group 2 . In conclusion , skin‐to‐skin contact produced an analgesic effect in preterm newborns during heel lancing This study evaluated a distraction intervention design ed to reduce the distress of preschool children undergoing repeated chemotherapy injections . Twenty-nine children aged 2 - 5 years were r and omly assigned either to distraction by a developmentally appropriate electronic toy or to a wait-list control . Children who received the distraction intervention demonstrated lower overt behavioral distress and were rated by parents and nurses as less anxious than children in the control condition . The improvements were maintained over the 8-week intervention . The results suggest that a developmentally appropriate , multisensory , variable-distracting activity that requires active cognitive processing and active motor responses may be a viable cost-effective alternative to more time-intensive parent-training programs for preschool-age children AIM Leg massage could inhibit the transmission of pain by ' closing the gate ' or by activating the endogenous opioid pathway to decrease nociceptive transmission of pain associated with heel stick . The aim of this study is to determine the effects of massage therapy prior to heel stick on responses assessed by the Neonatal Infant Pain Scale ( NIPS ) ( primary outcome ) , heart rate , respiratory rate and oxygen saturation ( secondary outcomes ) in infants who required a heel stick for blood sampling . METHODS This r and omised , double-blind , crossover trial with infants from 1 to 7 days post birth excluded those with prior surgery , septicaemia , current assisted ventilation or an analgesic within 48 h. After informed consent , 13 infants received a 2-min massage of the ipsilateral leg prior to heel stick on the first study sampling and no massage on the next sampling 2 - 7 days later and 10 infants had the reverse order . The bedside nurse , blinded to the intervention , measured NIPS , heart rate , respiratory rate , and oxygen saturation prior to massage , after massage , and 5 min after heel stick . Serum cortisol was measured with the blood sampling . RESULTS In 23 infants ( birthweight 795 - 2507 g ) , there were no adverse physiologic effects of massage . After heel stick , NIPS ( P < 0.001 ) and heart rate ( P = 0.03 ) were increased in the no-massage group compared with the massage group . Respiratory rate , oxygen saturation and serum cortisol were not significantly different . CONCLUSION Gentle massage of the leg prior to heel stick is safe and decreases pain responses in preterm infants BACKGROUND The purpose of this trial was to determine whether cobedding of preterm twins has analgesic effects during heel lancing or not . METHODS One hundred premature twins ( 50 sets ) born between 26 weeks ' and 34 weeks ' gestation undergoing heel blood sampling were r and omly assigned into two groups : the cobedding group ( receiving care in the same incubator ) and the st and ard care group ( receiving care in separate incubators ) . Pain was assessed using the premature infant pain profile score . Duration of crying was measured after heel blood sampling , and salivary cortisol was measured prior to and after heel blood sampling . RESULTS Infants in the st and ard care group cried for a longer time during heel lancing than those in the cobedding group ( 42.6 ± 19.8 seconds vs. 36.4 ± 21.7 seconds , p = 0.03 ) . The mean premature infant pain profile score after heel lancing was significantly higher in the st and ard care group ( 9.8 ± 2.6 vs. 8.06 ± 2.8 , p = 0.002 ) . The mean salivary cortisol after heel lancing was also significantly higher in the st and ard care group ( 24.3 ± 7.4 nmol/L vs. 20.8 ± 7.4 nmol/L , p = 0.02 ) . No significant adverse effects were seen with cobedding . CONCLUSION Cobedding is a comforting measure for twin premature infants during heel lancing , which can be performed without any significant adverse effects AIM AND OBJECTIVE This study aim ed to compare the effects of mother 's milk , sucrose and pacifier use to overcome pain during painful interventions to the newborns on the crying time and pain . BACKGROUND Various non-pharmacological methods are used to overcome the pain associated with painful interventions with newborns . DESIGN A prospect i ve , r and omised , controlled study involved 120 newborns in Turkey . METHODS The population consisted of healthy newborns hospitalised in the gynaecology clinics of Trabzon Delivery and Children 's Diseases hospital between February 2007-January 2008 . The newborns who had blood sampling by heel stick were divided into four groups : mother 's milk , sucrose , pacifier and control groups with 30 newborns in each . Data collection was performed using an information form on the newborn characteristics , which was developed by the research ers in the light of literature , clinical IR ear thermometer ET1 for temperature measurement , OXIMAX N-65 Pulse oxymeter for oxygen saturation and heart rate and neonatal infant pain scale for the measurement of the behavioural responses of newborns . Results . No differences were determined between the groups for heart rate and oxygen saturation in the newborns during painful interventions ( p > 0·05 ) . Sucrose followed by pacifier was the most effective method of reducing the crying time in the newborns . CONCLUSION The results indicate that all three practice s reduce the behavioural responses to pain at a higher rate than in the control group . RELEVANCE TO CLINICAL PRACTICE Health care personnel should perform painful interventions to the newborns while the babies are held by their mothers and during the procedure use of sucrose should be the primary choice OBJECTIVE . Local reactions are relatively common after the fifth diphtheria-tetanus-acellular pertussis vaccination , but factors associated with an increased risk of those reactions are not well defined . The objective of this study was to assess the relationship between needle length and injection site on the risk of local reactions to the fifth diphtheria-tetanus-acellular pertussis vaccination administered in the context of usual clinical care . METHODS . In this prospect i ve assessment , parents reported signs and symptoms of adverse events for 7 days after vaccination . The relative risk of adverse events in relation to needle length ( 16 or 25 mm ) and injection site ( arm or thigh ) was estimated in multivariate analyses that adjusted for age , gender , and BMI . RESULTS . Of the 1315 study participants , 89 % were vaccinated in the arm , and 67 % were vaccinated with a 25-mm needle . Among children vaccinated in the arm , use of the shorter 16-mm needle was associated with a significantly higher risk of any redness , ≥5 cm of redness , persistent redness on day 2 , and pain compared with vaccination with a 25-mm needle . Similar trends among the smaller group of children vaccinated in the thigh were also suggested but were not statistically significant . In analyses that were restricted to children vaccinated with a 25-mm needle , vaccination in the thigh versus arm was associated with a substantially lower risk of ≥5 cm of redness and a significantly lower risk of swelling and any itching but not with any difference in the risk of pain , irritability , or change in activity . CONCLUSIONS . These findings suggest that a 25-mm needle should be used for the fifth diphtheria-tetanus-acellular pertussis vaccination regardless of injection site and that vaccination in the thigh is an option that may be considered by parents and providers who would like to decrease the risk of local reactions characterized by redness and swelling Abstract Objectives : The effectiveness of skin-to-skin contact to decrease pain from heel-lancing in healthy term neonates and whether breastfeeding in addition to skin-to-skin contact provided a more effective analgesia than skin-to-skin contact alone were investigated . Methods : A r and omised , controlled trial was conducted in 107 neonates undergoing heel-lance . Infants were r and omly assigned to three groups : ( i ) being breastfed with skin-to-skin contact ( group 1 , n=35 ) , ( ii ) being held in their mother 's arms with skin-to-skin contact but no breastfeeding ( group 2 , n=36 ) , or ( iii ) lying on the table before , during and after painful stimulus ( group 3 , n=36 ) . Physiological responses to pain were measured by heart rate and oxygen saturation changes and behavioural responses were measured by duration of crying and grimacing . Results : Infants had a mean ( SD ) birthweight of 3355 ( 270 ) g and gestational age of 39.5 ( 0.6 ) weeks ; at the time of the procedure , mean ( SD ) postnatal age was 33.1 ( 5 ) hours . There was no significant difference between the groups in clinical characteristics and time spent squeezing the heel . Heart rate , oxygen saturation changes and length of crying were significantly reduced in groups 1 and 2 compared with group 3 ( p<0.001 ) . No difference was found between group 1 and group 2 . Grimacing was less in group 2 than in group 3 ( p<0.001 ) . Conclusions : In healthy term neonates , skin-to-skin contact with the mother and breastfeeding with skin-to-skin contact reduce both physiological and behavioural pain response . Breastfeeding in the 1st 2 postnatal days with skin-to-skin contact did not increase the analgesic effect of skin-to-skin contact alone OBJECTIVE To describe and underst and how mothers utilize the opportunity to actively participate in their preterm infants ' pain care using facilitated tucking by parents ( FTP ) . DESIGN Descriptive and exploratory study with postintervention interview . SETTING Finnish level III Neonatal Intensive Care Unit ( NICU ) . PARTICIPANTS Twenty-three mothers who had preterm infants born at gestational ages of 32 to 34 weeks . METHODS The parents ( N=45 ) of 29 preterm infants were taught to use FTP . In addition , all nurses in the NICU ( N=76 ) received the same education to support the parents ' use of FTP . After 2 to 4 weeks of FTP use , the mothers ( n=23 ) were interviewed using the Clinical Interview for Parents of High-Risk Infants with additional questions related to the infants ' pain care . The interviews were analyzed inductively with cross-case analysis and deductively with a previously developed coding scheme . RESULTS Facilitated tucking by parents was perceived positively and was used by all participating mothers . Three different styles of involvement in preterm infants ' pain care with FTP were identified . They formed a continuum from external to r and om and finally to internalized involvement . In external involvement , the pain care with FTP was triggered by outside factors such as nurses , whereas in r and om and internalized involvement the motivation emerged from a parent . Mothers with external involvement thought that any person could apply the FTP . In r and om involvement , mothers were mainly absent during painful procedures , although they saw themselves as the best caregivers . In internalized involvement , the responsibility for infant pain care was shared within the family . Mothers ' NICU-related stress and maternal attachment were associated with this variation . CONCLUSION This study showed that mothers ' are willing to actively participate in their preterm infants ' pain care . However , the participation is unique according to mother and her experiences before and during NICU admission . Nurses need to consider these differences in mothers when involving them in preterm infants ' pain care AIMS AND OBJECTIVES To determine the efficacy of swaddling and heel warming on pain response in neonates following heel stick . BACKGROUND Swaddling has been suggested to reduce pain response in neonates during heel stick . Heel warming is also often performed for drawing blood easily before heel stick . However , the efficacy of both on pain response is unclear . DESIGN A r and omised controlled study was used . METHODS Twenty-five neonates were r and omly assigned to each of the control , swaddling and heel-warming groups . Heart rate , oxygen saturation Neonatal Infant Pain Scale and duration of crying were used to assess pain reactivity and pain recovery . A greater heart rate and Neonatal Infant Pain Scale increase , or oxygen saturation decrease , indicated higher pain reactivity . A longer duration of heart rate and oxygen saturation changes after heel stick back to baseline indicated a longer pain recovery . RESULTS The decrease in oxygen saturation in swaddling group was significantly greater than that in heel-warming group . The increase in the Neonatal Infant Pain Scale in control group was significantly higher than that in swaddling group . The heart rate recovery time in control group and swaddling group was significantly longer than that in heel-warming group . The oxygen saturation recovery time in control group was significantly longer than that in heel-warming group . The duration of crying in control group was significantly longer than those in swaddling group and heel-warming group . CONCLUSION Both swaddling and heel warming decreased the pain response of neonates during heel stick . Heel warming result ed in a lower pain response than did swaddling for neonates , particularly in terms of pain recovery . RELEVANCE TO CLINICAL PRACTICE Heel warming could become a routine practice to decrease the pain response of neonates during heel stick OBJECTIVE To compare intraoperative efficiency and postoperative recovery between cold dissection adenotonsillectomy ( CDA ) and coblation-assisted adenotonsillectomy ( CAA ) . METHODS A prospect i ve , r and omized , single-blind trial of pediatric patients aged 2 to 16 years undergoing adenotonsillectomy was conducted . Patients were r and omized to undergo either CDA or CAA . Measured intraoperative parameters included surgical duration and intraoperative blood loss . Measured postoperative parameters included a 14 day caregiver question naire that recorded a daily pain rating using the Wong-Baker FACES pain scale , pain medication use , days to return to a normal diet , and days to return to a normal caregiver routine . Postoperative complications were also recorded . Intraoperative and postoperative measures were statistically compared between groups . RESULTS Forty-six children with a mean age of 6.7 years ( 23 CDA and 23 CAA ) were r and omized and completed the study . Mean age and sex distributions were similar between groups ( P > .05 ) . Surgical times were significantly shorter for the CAA group versus the CDA group ( 11.2 min vs. 17.0 min , P < .001 ) . Intraoperative blood loss was statistically lower for both the adenoidectomy and tonsillectomy portions of the procedure for the CAA group versus the CDA group ( P < .001 and P < .001 , respectively ) . There was no statistically significant difference in reported daily pain scores between groups ( P = .296 , analysis of variance ) . Both groups returned to normal diet ( P = .982 ) , and caregivers returned to their normal routine on similar postoperative days ( P = .631 ) . CONCLUSIONS CAA offers better operative speed and intraoperative hemostasis as compared with CDA . However , CAA does not result in poorer postoperative pain scores or recoveries despite these intraoperative advantages The purpose of the study was to compare a heel stick conducted during Kangaroo Care ( skin-to-skin contact ) with the mother to a heel stick in a warmer in reducing premature infant physiologic and behavioral pain responses . Twenty-four premature infants in a university-based neonatal intensive care unit were recruited and r and omized to 2 sequences : sequence A group received 3 hours of Kangaroo Care ( with a heel stick in Kangaroo Care ) followed by 3 hours in a warmer ( with a heel stick in the warmer ) . Sequence B group had warmer care and a heel stick ( in the warmer ) before Kangaroo Care and a heel stick ( in Kangaroo Care ) . Heart rate , respiratory rate , oxygen saturation , crying time , and behavioral state were measured before , during , and after heel stick . Repeated measures ANOVA and Mann Whitney U statistics were performed . Heart rate and length of crying in response to pain were significantly reduced during Kangaroo Care and the Kangaroo Care heel stick as compared to when infants were in the warmer and had a heel stick in the warmer . Three infants did not cry at all during the Kangaroo Care heel stick ; infants slept more during Kangaroo Care than in the warmer . Kangaroo Care positioning before and during heel stick is a simple and inexpensive analgesic intervention to ameliorate pain in stable premature infants This r and omized clinical trial employed a 2-group ( general child behavior management training vs. distraction for pain management training ) design across repeated parent-administered needle procedures . Forty-seven children with a chronic illness requiring recurrent injections were observed at baseline and 2 intervention sessions . Videotaped observations of parent – child interactions were coded for child behavioral distress and parents ' use of behavior management strategies . Across groups , many children displayed minimal to no distress at baseline . Among participants with significant distress , neither intervention group displayed consistently decreased procedural distress or increased use of child behavior management strategies OBJECTIVE : The goal was to compare the efficacy of oral 25 % dextrose treatment and /or skin-to-skin contact for analgesia in term newborns during intramuscular injection of a hepatitis B vaccine . METHODS : A prospect i ve , r and omized , partially blinded , clinical trial was performed with 640 healthy term newborns . Infants at 12 to 72 hours of life were assigned r and omly to receive an intramuscular injection of hepatitis B vaccine in the right thigh according to 4 analgesia groups , that is , no analgesia ( routine ) ; oral 25 % dextrose treatment , given 2 minutes before the injection ; skin-to-skin contact , initiated 2 minutes before the injection and persisting throughout the procedure ; and a combination of the oral dextrose treatment and skin-to-skin contact strategies . For all groups , Neonatal Facial Coding System and Neonatal Infant Pain Scale scores were evaluated before the procedure , during thigh cleansing , during the injection , and 2 minutes after the injection . Premature Infant Pain Profile scores also were assessed for all infants . Pain scores were compared among the 4 groups . RESULTS : The use of oral 25 % dextrose treatment reduced the duration of procedural pain in the studied population . Skin-to-skin contact decreased injection pain and duration . The combination of the 2 analgesic measures was more effective than either measure separately for term newborns . CONCLUSIONS : Nonpharmacologic analgesic measures were effective for the treatment of procedural pain in term infants . The combination of oral 25 % dextrose treatment and skin-to-skin contact acted synergistically to decrease acute pain in healthy neonates Objective : To determine the effectiveness of parent-led tactile stimulation for pain reduction when added to a combination of evidence -based pain-reducing interventions in infants undergoing immunization injections . Methods : Healthy infants aged 4 to 6 months undergoing routine immunization at a primary care practice were eligible . Infants were r and omized to tactile stimulation by a parent or usual care . Parents in the tactile stimulation group rubbed the ipsilateral thigh distal to the site for 15 seconds before , during , and after injections . In addition , all infants received evidence -based pain-relieving interventions including : sucrose solution , holding by a parent , and intramuscular injection without aspiration . The primary outcome was pain , measured by a vali date d tool , the Modified Behavioral Pain Scale ( MBPS ) , by an observer unaware of treatment allocation using videotapes of the procedure . MBPS scores could range from 0 ( no pain ) to 10 ( maximum pain ) . Parents , unaware of the study hypothesis , also rated infant pain in real time using a 100 mm visual analogue scale . Results : One hundred twenty infants participated . Infant characteristics did not differ ( P>0.05 ) between the tactile stimulation and control groups . Mean MBPS scores and parent visual analogue scale scores did not differ between groups ( 8.2 [ 1.1 ] vs. 8.0 [ 1.3 ] ; P=0.57 ) and ( 60 [ 20 ] vs. 53 [ 22 ] mm ; P=0.10 ) , respectively . Discussion : Parent-led tactile stimulation did not reduce pain in infants undergoing immunization injections when combined with other pain-relieving interventions . Potential reasons for the lack of effectiveness are discussed . Investigation of the effectiveness of clinician-led tactile stimulation in this population is recommended Infant procedural distress is largely understudied , and there is a dearth of empirically supported interventions in the child health psychology literature . This study examined nurse-directed distraction for reducing infant immunization distress . Ninety infants and their parents were r and omly assigned to a distraction condition ( i.e. , nurses used stimuli to divert infants ' attention ) or a typical care condition . Outcome measures were an observational scale , parent and nurse ratings , and infant heart rate . Results indicated that infants engaged in distraction and that distraction reduced their behavioral distress ; however , ratings and heart rate were inconclusive . Analyses of procedural phases indicated that infants exhibited elevated distress immediately prior to and during an injection , but this distress was fleeting BACKGROUND To compare the effectiveness of maternal breast milk odor and formula milk odor in soothing premature infants undergoing heel lancing . MATERIAL S AND METHODS Fifty preterm infants born between 32 weeks and 37 weeks gestation were r and omly assigned into two groups . During heel lancing , we used formula milk odor for the first group and breast milk odor for the second group . A filter paper ( containing either formula or breast milk ) was placed near the infant 's nose from 3 minutes prior to and up to 9 minutes after the heel blood sampling . The pain score was measured using premature infant pain profile ( PIPP ) score . We also evaluated crying duration and salivary cortisol prior to and after heel lancing . RESULTS After the heel lancing , the PIPP score was found to be significantly lower in the breast milk group than the formula milk group ( 5.4 compared to 9 with p < 0.001 ) . Also , the level of salivary cortisol had significantly increased in the formula milk group , but not in the breast milk group ( 25.3 nmol/L compared to 17.7 nmol/L ( p < 0.001 ) . CONCLUSION Breast milk odor has an analgesic effect in preterm newborns and can be used as a safe method for pain relief The effects of behavioral interventions in reducing the stress of infant pain are not well documented . Two comfort interventions , rocking and pacifiers , were compared with routine care administered to 60 newborn infants r and omly assigned to the three conditions following a neonatal screening heelstick . Heart rate , state of arousal , and crying were recorded continuously . Both pacifiers and rocking reduced crying , but pacifiers predominantly produced sleep states and rocking predominantly produced alert states . Pacifiers reduced heart rate levels significantly more than did rocking . Thus , newborns clearly benefit from both comforting methods . Several mechanisms are proposed to account for these findings Pain is traumatic for preterm infants and can damage their CNS . We wanted to assess whether multisensorial stimulation can be analgesic and whether this effect is only due to oral glucose or sucking . We performed a r and omized prospect i ve study , using a vali date d acute pain rating scale to assess pain during heel-prick combined with five different procedures : ( A ) control , ( B ) 10 % oral glucose plus sucking , ( C ) sensorial saturation ( SS ) , ( D ) oral water , and ( E ) 10 % oral glucose . SS is a multisensorial stimulation consisting of delicate tactile , vestibular , gustative , olfactory , auditory and visual stimuli . Controls did not receive any analgesia . We studied 85 heel-pricks ( 5 per baby ) performed for routine blood sample s in 17 preterm infants ( 28–35 weeks of gestational age ) . We applied in r and om order in each patient the five procedures described above and scored pain . SS and sucking plus oral glucose have the greater analgesic effect with respect to no intervention ( p < 0.001 ) . The effect of SS is statistically better than that of glucose plus sucking ( p < 0.01 ) . SS promotes interaction between nurse and infant and is a simple effective form of analgesia for the NICU BACKGROUND Procedural pain management for very low birth weight ( VLBW ) neonates has been minimal or nonexistent in most neonatal intensive care units ( NICUs ) . OBJECTIVES To compare the efficacy of developmentally sensitive behavioral interventions ( nonnutritive sucking via a pacifier , positioning ) and sucrose for relieving procedural pain in VLBW infants and to determine the influence of context ual factors ( gestational age , postnatal age , birth weight , severity of illness , frequency of painful procedures ) on pain response . METHOD In a prospect i ve r and omized crossover trial , pain was assessed in 122 VLBW neonates using the Premature Infant Pain Profile following four r and omly ordered interventions during consecutive routine heel lance procedures . RESULTS Significant differences in pain existed among treatment interventions ( F = 16.20 , p < .0001 ) . The pacifier with sucrose ( F = 24.09 , p < .0001 ) and pacifier with sterile water ( F = 9.00 , p = .003 ) significantly reduced pain . Prone positioning did not decrease pain ( F = 2.24 , p = .137 ) . Frequency of painful procedures approached significance in influencing pain response ( F = 3.59 , p = .01 ) . CONCLUSIONS The most efficacious interventions for reducing pain from single painful events were the pacifier with sucrose and the pacifier with sterile water . Research on the efficacy and safety of implementing these interventions , alone and in combination , for repeated painful procedures is needed . In addition , research is needed on the influence of implementing these interventions on pain response and clinical outcomes ( e.g. , health status and neurodevelopmental status ) in VLBW neonates in the NICU ISSUES AND PURPOSE Distraction during painful procedures has been shown to be effective in previous studies , yet this simple intervention is not used routinely . This study examined the effectiveness and feasibility of distraction in reducing behavioral distress , pain , and fear during venipuncture or intravenous insertion . DESIGN AND METHODS A two-group r and omized design with 384 children in 13 children 's hospitals . RESULTS Age was a significant factor in observed behavioral distress , reports of fear , and self-reported pain . The use of a kaleidoscope , however , did not significantly reduce pain or distress during venipuncture or i.v . insertion . PRACTICE IMPLICATION S Failure of the distraction intervention to reach statistical significance in this study is puzzling , given anecdotal reports of clinical efficacy . Method ological issues may have obscured actual differences between experimental and control groups BACKGROUND Several authors have reported on laparoscopic pyloromyotomy ( LP ) since the technique was originally described in 1990 , but its benefits remain unproven . We performed a r and omized controlled trial comparing LP to open circumumbilical pyloromyotomy ( OP ) for hypertrophic pyloric stenosis . METHODS In a prospect i ve study , 102 infants with pyloric stenosis were r and omly assigned to either LP ( n = 50 ) or OP ( n = 52 ) . The primary outcome measure was the incidence of postoperative vomiting ; the secondary parameters were the duration s of surgery and anesthesia , surgical complications , and postoperative pain . All infants were managed according to st and ardized procedures regarding general anesthesia , surgical technique , postoperative analgesia , and feeding regimen . Parents , carers , and assessors responsible for the postoperative evaluation were blinded for the technique used . RESULTS There was no difference in the incidence of postoperative vomiting between the 2 groups . The overall incidence of complications was similar , but the duration s of surgery and general anesthesia were significantly longer in the LP group than in the OP group ( P = 10(-4 ) and P = .02 , respectively ) . There were 3 cases of incomplete pyloromyotomy after laparoscopy , requiring a repeat procedure . CONCLUSIONS Laparoscopic pyloromyotomy does not decrease the incidence of postoperative vomiting , has a similar complication rate compared with the open umbilical approach , but may expose patients to a risk of inadequate pyloromyotomy Background : Preterm neonates below 30 weeks ’ gestational age undergo numerous painful procedures . Many management approaches are not appropriate for this population . Therapeutic Touch , an alternative approach based on the theory of energy medicine , has been shown to promote physiological stability in preterm neonates and reduce pain in some adult studies . The objective was to determine whether Therapeutic Touch is efficacious in decreasing pain in preterm neonates . Methods : Infants < 30 weeks ’ gestational age participated in a r and omized control trial in 2 level III neonatal intensive care units . All evaluations , analyses , and heel lance procedure were conducted with only the therapist knowing the group assignment . Immediately before and after the heel lance procedure , the therapist performed nontactile Therapeutic Touch ( n=27 ) with infant behind curtains , leaving the curtained area for the heel lance , performed by another . In the sham condition ( n=28 ) , the therapist stood by the incubator with h and s by her side . The Premature Infant Pain Profile was used for pain response and time for heart rate to return to baseline for recovery . Heart rate variability and stress response were secondary outcomes . Results : There were no group differences in any of the outcomes . Mean Premature Infant Pain Profile scores across 2 minutes of heel lance procedure in 30-second blocks ranged from 7.92 to 8.98 in the Therapeutic Touch group and 7.64 to 8.46 in the sham group . Interpretation : Therapeutic Touch given immediately before and after heel lance has no comforting effect in preterm neonates . Other effective strategies involving actual touch should be considered BACKGROUND Pain and stress agitate preterm infants , interrupting their sleep . Frequent high arousal states may affect infants ' brain development and illness recovery . Preserving infants ' sleep and relieving their pain during painful procedures are both important for their health . OBJECTIVES To compare the effectiveness of different combinations of non-nutritive sucking ( sucking ) , oral sucrose , and facilitated tucking ( tucking ) with routine care on infants ' sleep-wake states before , during , and after heel-stick procedures . DESIGN Prospect i ve , r and omised controlled trial . SETTING Level III Neonatal Intensive Care Unit in Taipei . METHOD A convenience sample of 110 infants ( gestational age 26.4 - 37 weeks ) needing heel sticks were r and omly assigned to five combinations of non-pharmacological treatments : sucking-oral sucrose-tucking ; sucking-oral sucrose ; oral sucrose-tucking ; sucking-tucking ; and routine care . Infant states , measured by a state-coding scheme , included quiet sleep , active sleep , transition , quiet awake , active awake , and fussing or crying . All states were recorded at 1-min intervals during four phases : baseline , intervention , heel-stick procedures , and recovery . RESULTS Infants receiving sucking-oral sucrose-tucking or sucking-oral sucrose experienced 52.8 % ( p=0.023 ) and 42.6 % ( p=0.063 ) more quiet-sleep occurrences than those receiving routine care after adjusting for phase , baseline states , non-treatment sucking during baseline and recovery , positioning , and infants ' characteristics . Infants receiving oral sucrose-tucking , sucking-oral sucrose , sucking-oral sucrose-tucking , and sucking-tucking experienced 77.3 % ( p<0.001 ) , 72.1 % ( p=0.008 ) , 51.5 % ( p=0.017 ) , and 33.0 % ( p=0.105 ) fewer occurrences of fussing or crying , respectively , than those receiving routine care after adjusting for related factors . CONCLUSIONS The four treatment combinations differentially reduced infants ' high arousal across heel-stick procedures . The combined use of oral sucrose-tucking , sucking-oral sucrose , and sucking-oral sucrose-tucking more effectively reduced occurrences of infant fussing or crying than routine care . Treatment combinations of sucking-oral sucrose-tucking and sucking-oral sucrose also better facilitated infants ' sleep than routine care . To preserve infants ' sleep , clinicians should use combinations of non-nutritive sucking , oral sucrose , and facilitated tucking to reduce agitation during painful procedures This r and omized controlled trial compared distress and pain in healthy 4-month-old infants receiving three different immunizations either sequentially ( control , n=50 ) or simultaneously , two at the same time , followed by the third ( experimental , n=51 ) . Although both groups demonstrated a significant increase in cortisol from baseline levels , the lack of significant difference on salivary cortisol between groups post-immunization suggests the study was underpowered . On NIPS scores , the experimental group demonstrated significantly less pain ( Mann-Whitney U=1648.0 , p=0.003 ) . Simultaneous injections appeared to be effective in reducing pain behavior responses in infants receiving their 4-month immunizations . Longitudinal studies could determine whether reduced exposure to pain in infancy , through simultaneous immunization injections , could contribute to a reduction in sensitivity to pain and physiologic stress responses Pain and distress during immunisation of toddlers are reasons for non-immunisation of large number of toddlers . The present study was undertaken to assess the comparative effectiveness of distraction techniques in the process of immunisation i.e. toy and music . ( The third group of study subjects was control group ) . It is concluded that distraction techniques are quite economical and safe in enhancing the magnitude of immunisation Background and Objectives : Previous r and omized trials of the analgesic effects of sucrose , glucose , and a pacifier in term neonates have shown that the pacifier result ed in lower pain scores than glucose or sucrose , but the pacifier with and without sucrose did not differ . The current study was design ed to assess the analgesic effect of pharmacologic ( sucrose , water ) and a non-pharmacologic measures ( pacifier ) in preterm infants and to find whether there is any synergism between these intervention in relieving pain during painful procedures . Patients and Methods : In this double-blind , r and omized , controlled study , 36 preterm infants ( mean 31 weeks gestational age , range 27 to 36 weeks ) were r and omly allocated to six different regimens ( 0.5 mL sterile water with pacifier , 0.5 mL sterile water without pacifier , 0.5 mL sucrose 24 % with pacifier , 0.5 mL sucrose 24 % without pacifier , pacifier alone and control group ) during a stay in intensive care of up to 15 days . Pain scores were measured with the Premature Infant Pain Profile ( PIPP ) , a vali date d behavioral acute pain scale . Results : Of all the regimens , the lowest pain scores occurred with the use of 24 % sucrose solution combined with pacifier . The mean pain score for the combination of sucrose with pacifier was 0.7 as compared to 1.4 for the sterile water with pacifier group ( P < .05 ) . Conclusion : The synergistic effect of the combination of sucrose and non-nutritive sucking was clinical ly effective and safe in relieving the pain of simple procedures such as venipuncture or heel stick in preterm and term infants , but further research is needed on these interventions alone and in combination with other behav -- ioral interventions in neonates OBJECTIVE To determine if acute pain response after administration of the diphtheria , polio , and tetanus toxoids and acellular pertussis and Haemophilus influenzae type b ( DPTaP-Hib ) vaccine and the pneumococcal conjugate vaccine ( PCV ) is affected by the order in which they are given . DESIGN Single-center , double-blind , r and omized clinical trial . SETTING Outpatient pediatric clinic in Toronto , Ontario , Canada . PARTICIPANTS Healthy infants 2 to 6 months of age undergoing routine immunization . INTERVENTIONS Infants received either their primary DPTaP-Hib vaccine or the PCV first , followed by the other vaccine . MAIN OUTCOME MEASURES The primary outcome was infant pain during vaccine injection as assessed by a vali date d measure , the Modified Behavioral Pain Scale ( MBPS ) , using videotaped recordings of the procedure . In addition , parents rated pain using a 10-cm visual analog scale ( VAS ) . Crying ( yes/no ) was also measured . RESULTS The study was conducted between July 21 , 2006 , and June 21 , 2007 . A total of 120 infants participated : 60 received the DPTaP-Hib vaccine first and 60 received the PCV first . Infant characteristics did not differ between groups . Overall mean ( SD ) pain scores per infant after receiving both vaccine injections were significantly lower when DPTaP-Hib was administered first compared with when PCV was administered first ( MBPS score , 7.6 [ 1.5 ] vs 8.2 [ 1.5 ] , P = .037 ; parent VAS score , 4.2 [ 2.3 ] vs 5.6 [ 2.6 ] , P = .003 ) . When given first , the DPTaP-Hib vaccine caused significantly less pain ( P < .001 ) than the PCV , as assessed by the MBPS , VAS , and crying . CONCLUSIONS Pain was reduced when the DPTaP-Hib vaccine was administered before the PCV in infants undergoing routine vaccination . We recommend that the order of vaccine injections be the DPTaP-Hib vaccine followed by the PCV OBJECTIVE The aim of the study was to determine the efficacy of ShotBlocker ( Bionix , Toledo , Ohio ) in reducing pediatric pain with intramuscular ( IM ) injections . METHODS A prospect i ve r and omized controlled trial was conducted in children aged 2 months to 17 years who required an IM injection . Children were r and omized to the no-intervention group or the ShotBlocker group . Demographic data and the number of IM injections were recorded . Perceived pain scores were obtained from nurses and caregivers using a 6-point Likert-type scale . Baker Wong Faces scale was used in children 36 months or older . Difficulty using the device was also rated by nurses on a 6-point scale . RESULTS One hundred sixty-five children were enrolled with 80 in the no-intervention arm and 85 in the ShotBlocker arm . The mean age of children was 45 months and 56 % were male . Perceived pain scores by nurses were higher for the no-intervention group ( 2.6 vs 1.8 , P < .001 ) as well as by caregivers ( 2.6 vs 2.1 , P = .04 ) . Children aged 36 months and older ( n = 64 ) did not report a difference in pain scores ( 1.5 vs 1.3 , P = .6 ) ; however , in a subgroup of children 72 months or older , pain scores trended higher in the no-intervention group ( 1.3 vs 0.5 , P = .051 ) . Nurse-perceived difficulty of ShotBlocker use was low 1.39 ( + /-1.1 ) . CONCLUSIONS Nurses and caregivers noted lower pain scores in children assigned to the ShotBlocker group . These differences were not as evident when children rated their own pain Objectives The purpose of this study was to compare the effectiveness of “ facilitated tucking by parents ” ( FTP ) in which a parent holds by her h and s the infant in a side-lying flexed position offering support and skin contact , oral glucose , opioid ( oxycodone ) , and placebo ( oral water ) in the context of heel stick and pharyngeal suctioning in very preterm infants . We hypothesized that nonpharmacologic methods equal the pharmacologic method and are superior to placebo in pain management . Methods A prospect i ve r and omized placebo-controlled crossover trial . The study patients ( n=20 ) were born at a mean gestational age of 28 + 1 weeks and were studied at postconceptional age of 28 to 32 weeks . Pain measurements with Premature Infant Pain Profile and Neonatal Infant Pain Scale covered the first 30 seconds after the beginning of the painful stimulus . Results Premature Infant Pain Profile scores were significantly lower with oral glucose ( mean : 4.85±1.73 , P≤0.001 ) and FTP ( mean : 5.20±1.70 , P=0.004 ) when compared with placebo ( mean : 7.05±2.16 ) after heel stick . During pharyngeal suctioning , the scores were lowest with oral glucose ( mean : 11.05±2.31 , P=0.014 ) and FTP ( mean : 11.25±2.47 , P=0.034 ) compared with placebo ( mean : 12.40±2.06 ) . Opioid equaled placebo in both procedures . Neonatal Infant Pain Scale scores were significantly lower with FTP ( P≤0.001 ) and opioid ( P=0.018 ) after heel stick , and during pharyngeal suctioning with FTP ( P=0.001 ) compared with placebo . We found significantly more short-term adverse effects per administration with oral glucose ( 21.25 % ) and oral water ( 12.5 % ) compared with opioid ( 5 % ) or FTP ( 5 % ) . Discussion Our study demonstrated that FTP is not just equal , but preferable to other pain management methods when both efficacy and safety are considered BACKGROUND It was long believed that newborns could not experience pain . As it is now documented that newborns have all the necessary systems to perceive pain , pain management can no longer be ignored . The objective of this study is to investigate which concentration of glucose is most effective in reducing pain for venipuncture in the newborn . METHODS This double-blind clinical trial of 304 newborns was conducted on a maternity and neonatal ward ( neonatal medium intensive care unit ) . During at least 1 month , one of the four selected solutions ( 10 , 20 , 30 % glucose , and placebo ) was administered orally , 2 minutes before the venipuncture was performed . The pain from the skin puncture was scored using a vali date d pain scale ( the " Leuven Pain Scale " ) . RESULTS This study showed a significantly lower average pain score in the 30 percent glucose group ( 3.99 ) when compared with the placebo group ( 8.43 ) . The average pain scores in the 20 percent glucose group ( 5.26 ) and the 10 percent glucose group ( 5.92 ) were also significantly lower than those in the placebo group . CONCLUSION Oral administration of 2 mL of 30 percent glucose 2 minutes before the venipuncture provides the most effective pain reduction in newborns Objective : To compare acute pain response during immunisation in infants using a slow st and ard of care injection technique versus a rapid pragmatic technique . Design : R and omised controlled trial . Setting : Single-centre , urban paediatric primary care practice . Subjects : Healthy infants 4–6 months of age receiving their routine DPTaP-Hib immunisation . Interventions : St and ard of care group : slow aspiration prior to injection , slow injection and slow withdrawal . Pragmatic group : no aspiration , rapid injection and rapid withdrawal . Main outcome measures : Immediate infant pain measured by the Modified Behavior Pain Scale ( MBPS ) , crying and parent/paediatrician visual analogue scale ( VAS ) . Results : 113 infants participated ; there were no observed differences in age , birth order or prior analgesic use . Mean MBPS scores ( 95 % confidence interval ( CI ) ) were higher ( p<0.001 ) for the st and ard group compared to the pragmatic group , 5.6 ( 5 to 6.3 ) vs 3.3 ( 2.6 to 3.9 ) . The st and ard group was more likely to cry , 47/57 ( 82 % ) vs 24/56 ( 43 % ) , to cry longer , median ( interquartile range ( IQR ) ) 14.7 s ( 8.7–35.6 ) vs 0 s ( 0–11.30 ) , and to take longer to have the vaccine injected , median ( IQR ) 8.8 s ( 7.9–10.3 ) vs 0.9 s ( 0.8–1.1 ) , p<0.001 for all comparisons . The median ( IQR ) VAS scores by parents and paediatricians were higher for the st and ard group : VAS parent , 3.5 ( 1.6–5.5 ) vs 1.9 ( 0.1–3.1 ) and VAS paediatrician , 2.8 ( 2.0–5.1 ) vs 1.4 ( 0.2–2.4 ) . There were no adverse events . Conclusion : Immunisation using a pragmatic rapid injection technique is less painful than a slow st and ard of care technique and should be recommended for routine intramuscular immunisations OBJECTIVE : Pain experience can alter clinical outcome , brain development , and subsequent behavior in newborns , primarily in preterm infants . The aims of this study were ( 1 ) to evaluate several simple , commonly used methods for pain control in newborns and ( 2 ) to evaluate the concordance between behavioral and autonomic cardiac reactivity to pain in term neonates during heel-lancing . METHODS : A prospect i ve study was conducted of 180 term newborn infants who were undergoing heel-lancing for routine neonatal screening of phenylketonuria and hypothyroidism . Newborns were assigned to 6 groups : ( 1 ) control ( no pain relief intervention ) ; ( 2 ) nonnutritive sucking ; ( 3 ) holding by mother ; ( 4 ) oral glucose solution ; ( 5 ) oral formula feeding ; or ( 6 ) breastfeeding . Outcome measures included the Neonatal Facial Coding System score ; cry duration ; and autonomic variables obtained from spectral analysis of heart rate variability before , during , and after heel-lancing . RESULTS : Infants with no pain control showed the highest pain manifestation compared with newborns to whom pain control was provided . Infants who breastfed or received an oral formula showed the lowest increase in heart rate ( 21 and 23 beats per minute , respectively , vs 36 ; P < .01 ) , lowest neonatal facial score ( 2.3 and 2.9 , respectively , vs 7.1 ; P < .001 ) , lowest cry duration ( 5 and 13 seconds , respectively , vs 49 ; P < .001 ) , and lowest decrease in parasympathetic tone ( −2 and −2.4 , respectively , vs 1.2 ; P < .02 ) compared with the other groups . CONCLUSIONS : Any method of pain control is better than none . Feeding and breastfeeding during heel-lancing were found to be the most effective methods of pain relief BACKGROUND : Gavage feeding is required in preterm infants who can not feed by themselves . Insertion of the feeding tube is painful , and reducing the discomfort in these patients is desirable . OBJECTIVE : The aim of this study was to assess pain and discomfort during nasal insertion of a feeding tube , and to evaluate different measures for pain relief . METHODS : We included 24 preterm infants with postmenstrual age 28 to 32 weeks ' who were in stable condition . Each infant acted as his or her own control over a 3-week period during which the tube was changed 6 times . On these occasions , 6 different treatment combinations were given in r and omized order : pacifier or no pacifier , combined with no fluid , sterile water , or 30 % sucrose . Pain and discomfort were assessed by at least 2 independent and experienced observers using a pain assessment tool , the Premature Infant Pain Profile ; score range : 0 to 21 . In general , scores of 4 to 6 are interpreted as normal or no discomfort ; ≥12 usually signals significant pain and distress . RESULTS : The median Premature Infant Pain Profile score during the procedure was 9 and decreased gradually toward 4 after 5 minutes . The lowest pain score was achieved by combining a pacifier with oral sucrose . Sterile water without a pacifier gave the highest score . CONCLUSIONS : Insertion of a feeding tube in preterm infants leads to a measurable degree of pain and discomfort , according to the Premature Infant Pain Profile assessment tool . Pain relief was best achieved by combining a pacifier with 30 % sucrose |
10,325 | 27,780,893 | Conclusion : Environmental work site interventions to reduce sedentary behavior show promise because work sites often have more control over environmental factors . | Objective : The purpose of this investigation was to systematic ally review work site – based , environmental interventions to reduce sedentary behavior following preferred reporting items for systematic review s and meta-analyses guidelines . | Background Occupational sedentary behaviour is an important contributor to overall sedentary risk . There is limited evidence for effective workplace interventions to reduce occupational sedentary time and increase light activity during work hours . The purpose of the study was to determine if participatory workplace interventions could reduce total sedentary time , sustained sedentary time ( bouts > 30 minutes ) , increase the frequency of breaks in sedentary time and promote light intensity activity and moderate/vigorous activity ( MVPA ) during work hours . Methods A r and omised controlled trial ( ANZCTR number : ACTN12612000743864 ) was conducted using clerical , call centre and data processing workers ( n = 62 , aged 25–59 years ) in 3 large government organisations in Perth , Australia . Three groups developed interventions with a participatory approach : ‘ Active office ’ ( n = 19 ) , ‘ Active Workstation ’ and promotion of incidental office activity ; ‘ Traditional physical activity ’ ( n = 14 ) , pedometer challenge to increase activity between productive work time and ‘ Office ergonomics ’ ( n = 29 ) , computer workstation design and breaking up computer tasks . Accelerometer ( ActiGraph GT3X , 7 days ) determined sedentary time , sustained sedentary time , breaks in sedentary time , light intensity activity and MVPA on work days and during work hours were measured before and following a 12 week intervention period . Results For all participants there was a significant reduction in sedentary time on work days ( −1.6 % , p = 0.006 ) and during work hours ( −1.7 % , p = 0.014 ) and a significant increase in number of breaks/sedentary hour on work days ( 0.64 , p = 0.005 ) and during work hours ( 0.72 , p = 0.015 ) ; there was a concurrent significant increase in light activity during work hours ( 1.5 % , p = 0.012 ) and MVPA on work days ( 0.6 % , p = 0.012 ) . Conclusions This study explored novel ways to modify work practice s to reduce occupational sedentary behaviour . Participatory workplace interventions can reduce sedentary time , increase the frequency of breaks and improve light activity and MVPA of office workers by using a variety of interventions . Trial Registration Australian New Zeal and Clinical Trials Registry ACTN12612000743864 PURPOSE Although moderate-to-vigorous physical activity is related to premature mortality , the relationship between sedentary behaviors and mortality has not been fully explored and may represent a different paradigm than that associated with lack of exercise . We prospect ively examined sitting time and mortality in a representative sample of 17,013 Canadians 18 - 90 yr of age . METHODS Evaluation of daily sitting time ( almost none of the time , one fourth of the time , half of the time , three fourths of the time , almost all of the time ) , leisure time physical activity , smoking status , and alcohol consumption was conducted at baseline . Participants were followed prospect ively for an average of 12.0 yr for the ascertainment of mortality status . RESULTS There were 1832 deaths ( 759 of cardiovascular disease ( CVD ) and 547 of cancer ) during 204,732 person-yr of follow-up . After adjustment for potential confounders , there was a progressively higher risk of mortality across higher levels of sitting time from all causes ( hazard ratios ( HR ) : 1.00 , 1.00 , 1.11 , 1.36 , 1.54 ; P for trend < 0.0001 ) and CVD ( HR:1.00 , 1.01 , 1.22 , 1.47 , 1.54 ; P for trend < 0.0001 ) but not cancer . Similar results were obtained when stratified by sex , age , smoking status , and body mass index . Age-adjusted all-cause mortality rates per 10,000 person-yr of follow-up were 87 , 86 , 105 , 130 , and 161 ( P for trend < 0.0001 ) in physically inactive participants and 75 , 69 , 76 , 98 , 105 ( P for trend = 0.008 ) in active participants across sitting time categories . CONCLUSIONS These data demonstrate a dose-response association between sitting time and mortality from all causes and CVD , independent of leisure time physical activity . In addition to the promotion of moderate-to-vigorous physical activity and a healthy weight , physicians should discourage sitting for extended periods Even when adults meet physical activity guidelines , sitting for prolonged periods can compromise metabolic health . Television ( TV ) time and objective measurement studies show deleterious associations , and breaking up sedentary time is beneficial . Sitting time , TV time , and time sitting in automobiles increase premature mortality risk . Further evidence from prospect i ve studies , intervention trials , and population -based behavioral studies is required Objective : To evaluate the effectiveness of a 3-month treadmill desk intervention in eliciting changes in physical activity and sedentary behavior among overweight/obese office workers . Methods : A r and omized controlled trial was conducted among overweight/obese office workers ( n = 41 ; mean age = 40.1 ± 10.1 years ) at a private workplace . Participants were r and omly assigned to a shared-treadmill desk intervention ( n = 21 ) or a usual working condition control group ( n = 20 ) . Accelerometer-determined physical activity and sedentary behavior were measured before and after the intervention . Results : Compared with the control group , the intervention group increased daily steps ( 1622 steps/day ; P = 0.013 ) and light physical activity ( 1.6 minutes/hour ; P = 0.008 ) , and decreased sedentary time ( −3.6 minutes/hour ; P = 0.047 ) during working hours . Conclusions : Shared-treadmill desks in the workplace can be effective at promoting favorable changes in light physical activity ( specifically 40 to 99 steps/minute ) and sedentary behavior among overweight/obese office workers Background Prolonged sitting time is detrimental for health . Individuals with desk-based occupations tend to sit a great deal and sit-st and workstations have been identified as a potential strategy to reduce sitting time . Hence , the objective of the current study was to examine the effects of using sit-st and workstations on office workers ’ sitting time at work and over the whole day . Methods We conducted a r and omized controlled trial pilot with crossover design and waiting list control in Sydney , Australia from September 2011 to July 2012 ( n = 42 ; 86 % female ; mean age 38 ± 11 years ) . Participants used a sit-st and workstation for four weeks in the intervention condition . In the time-matched control condition , participants received nothing and crossed over to the intervention condition after four weeks . The primary outcomes , sitting , st and ing and walking time at work , were assessed before and after using the workstations with ActivPALs and self-report question naires . Secondary outcomes , domain-specific sitting over the whole day , were assessed by self-report . Linear mixed models estimated changes in outcomes adjusting for measurement time , study grouping and covariates . Results Intervention participants significantly reduced objective ly assessed time spent sitting at work by 73 min/workday ( 95 % CI : -106,-39 ) and increased st and ing time at work by 65 min/workday ( 95 % CI : 47 , 83 ) ; these changes were significant relative to controls ( p = 0.004 and p < 0.001 , respectively ) . Total sitting time significantly declined in intervention participants ( -80 min/workday ; 95 % CI : -155 , -4 ) . Conclusions This study shows that introducing sit-st and workstations in the office can reduce desk-based workers ’ sitting time at work in the short term . Larger scale studies on more representative sample s are needed to determine the public health impact of sit-st and workstations . Trial registration Objectives To test the efficacy of a multicomponent technology intervention for reducing daily sedentary time and improving cardiometabolic disease risk among sedentary , overweight university employees . Design Blinded , r and omised controlled trial . Setting A large south-eastern university in the USA . Participants 49 middle-aged , primarily female , sedentary and overweight adults working in sedentary jobs enrolled in the study . A total of 40 participants completed the study . Interventions Participants were r and omised to either : ( 1 ) an intervention group ( N=23 ; 47.6 + 9.9 years ; 94.1 % female ; 33.2 + 4.5 kg/m2 ) ; ( 2 ) or wait-list control group ( N=17 ; 42.6 + 8.9 years ; 86.9 % female ; 31.7 + 4.9 kg/m2 ) . The intervention group received a theory-based , internet-delivered programme , a portable pedal machine at work and a pedometer for 12 weeks . The wait-list control group maintained their behaviours for 12 weeks . Outcome measures Primary ( sedentary and physical activity behaviour measured objective ly through StepWatch ) and secondary ( heart rate , blood pressure , height , weight , waist circumference , per cent body fat , cardiorespiratory fitness , fasting lipids ) outcomes were measured at baseline and postintervention ( 12 weeks ) . Exploratory outcomes including intervention compliance and process evaluation measures were also assessed postintervention . Results Compared to controls , the intervention group reduced daily sedentary time ( mean change ( 95%CI ) : −58.7 min/day ( −118.4 to 0.99 ; p<0.01 ) ) after adjusting for baseline values and monitor wear time . Intervention participants logged on to the website 71.3 % of all intervention days , used the pedal machine 37.7 % of all working intervention days and pedalled an average of 31.1 min/day . Conclusions These findings suggest that the intervention was engaging and result ed in reductions in daily sedentary time among full-time sedentary employees . These findings hold public health significance due to the growing number of sedentary jobs and the potential of these technologies in large-scale worksite programmes . Trial Registration Clinical Trials.gov # NCT01371084 Introduction The objective of this study was to assess change in sitting and physical activity behavior in response to a workplace intervention to disrupt prolonged sitting time . Methods Sixty office workers were r and omized to either a St and group ( n = 29 ) , which received hourly prompts ( computer-based and wrist-worn ) to st and up , or a Step group ( n = 31 ) , which received the same hourly prompts and an additional prompt to walk 100 steps or more upon st and ing . An ActivPAL monitor was used to assess sitting and physical activity behavior on the same 3 consecutive workdays during baseline and intervention periods . Mixed-effect models with r and om intercepts and r and om slopes for time were performed to assess change between groups and across time . Results Both groups significantly reduced duration of average sitting bouts ( St and group , by 16 % ; Step group , by 19 % ) and the number of sitting bouts of 60 minutes or more ( Step group , by 36 % ; St and group , by 54 % ) . The St and group significantly reduced total sitting time ( by 6.6 % ) , duration of the longest sitting bout ( by 29 % ) , and number of sitting bouts of 30 minutes or more ( by 13 % ) and increased the number of sit-to-st and transitions ( by 15 % ) and st and ing time ( by 23 % ) . Stepping time significantly increased in the St and ( by 14 % ) and Step ( by 29 % ) groups , but only the Step group significantly increased ( by 35 % ) the number of steps per workday . Differences in changes from baseline to intervention between groups were not significant for any outcome . Conclusion Interventions that focus on disrupting sitting time only in the workplace may result in less sitting . When sitting time disruptions are paired with a physical activity prompt , people may be more likely to increase their workday physical activity , but the effect on sitting time may be attenuated Objective : This study was conducted to determine whether installation of sit-st and desks ( SSDs ) could lead to decreased sitting time during the workday among sedentary office workers . Methods : A r and omized cross-over trial was conducted from January to April , 2012 at a business in Minneapolis . 28 ( nine men , 26 full-time ) sedentary office workers took part in a 4 week intervention period which included the use of SSDs to gradually replace 50 % of sitting time with st and ing during the workday . Physical activity was the primary outcome . Mood , energy level , fatigue , appetite , dietary intake , and productivity were explored as secondary outcomes . Results : The intervention reduced sitting time at work by 21 % ( 95 % CI 18%–25 % ) and sedentary time by 4.8 min/work-hr ( 95 % CI 4.1–5.4 min/work-hr ) . For a 40 h work-week , this translates into replacement of 8 h of sitting time with st and ing and sedentary time being reduced by 3.2 h. Activity level during non-work hours did not change . The intervention also increased overall sense of well-being , energy , decreased fatigue , had no impact on productivity , and reduced appetite and dietary intake . The workstations were popular with the participants . Conclusion : The SSD intervention was successful in increasing work-time activity level , without changing activity level during non-work hours BACKGROUND Prolonged sitting is prevalent in the workplace and is associated with adverse health markers . PURPOSE Investigate the effects of point-of-choice ( PoC ) prompting software , on the computer used at work ( PC ) , to reduce long uninterrupted sedentary periods and total sedentary time at work . DESIGN Assessor-blinded , parallel group , active-controlled r and omized trial . SETTING / PARTICIPANTS A convenience sample of office workers from Glasgow , United Kingdom . Data were collected April to June 2010 , and analyzed October 2010 to June 2011 . INTERVENTION The education group ( n=14 ) received a brief education session on the importance of reducing long sitting periods at work . The PoC group ( n=14 ) received the same education along with prompting software on their PC for 5 workdays , which reminded them to st and up every 30 minutes . MAIN OUTCOME MEASURES Sitting time was measured objective ly using the activPAL ™ activity monitor for 5 workdays at baseline and 5 workdays during the intervention . The number and time spent sitting in events > 30 minutes ' duration were the main outcome measures . RESULTS At baseline , participants spent 5.7±1.0 hours/day ( 76%±9 % ) of their time at work sitting . Of that time , 3.3±1.3 hours/day was spent sitting in 3.7±1.4 events > 30 minutes . There was a significant difference between the groups in the change ( intervention to baseline ) of both the number ( ANCOVA ; -6.8 % , p=0.014 ) and duration ( -15.5 % , p=0.007 ) of sitting events > 30 minutes . During the intervention , compared with baseline , the PoC group reduced the number ( paired t-test ; -0.11 events/hour , p=0.045 ) and duration ( -12.2 % , p=0.035 ) of sitting events > 30 minutes . However , there was no significant difference in total sitting time between groups ( -4.4 % , p=0.084 ) . CONCLUSIONS Point-of-choice prompting software on work computers recommending taking a break from sitting plus education is superior to education alone in reducing long uninterrupted sedentary periods at work . TRIAL REGISTRATION This trial was registered at Clinical Trials.govNCT01628861 BACKGROUND Desk-based office employees sit for most of their working day . To address excessive sitting as a newly identified health risk , best practice frameworks suggest a multi-component approach . However , these approaches are re source intensive and knowledge about their impact is limited . PURPOSE To compare the efficacy of a multi-component intervention to reduce workplace sitting time , to a height-adjustable workstations-only intervention , and to a comparison group ( usual practice ) . DESIGN Three-arm quasi-r and omized controlled trial in three separate administrative units of the University of Queensl and , Brisbane , Australia . Data were collected between January and June 2012 and analyzed the same year . SETTING / PARTICIPANTS Desk-based office workers aged 20 - 65 ( multi-component intervention , n=16 ; workstations-only , n=14 ; comparison , n=14 ) . INTERVENTION The multi-component intervention comprised installation of height-adjustable workstations and organizational-level ( management consultation , staff education , manager e-mails to staff ) and individual-level ( face-to-face coaching , telephone support ) elements . MAIN OUTCOME MEASURES Workplace sitting time ( minutes/8-hour workday ) assessed objective ly via activPAL3 devices worn for 7 days at baseline and 3 months ( end-of-intervention ) . RESULTS At baseline , the mean proportion of workplace sitting time was approximately 77 % across all groups ( multi-component group 366 minutes/8 hours [ SD=49 ] ; workstations-only group 373 minutes/8 hours [ SD=36 ] , comparison 365 minutes/8 hours [ SD=54 ] ) . Following intervention and relative to the comparison group , workplace sitting time in the multi-component group was reduced by 89 minutes/8-hour workday ( 95 % CI=-130 , -47 minutes ; p<0.001 ) and 33 minutes in the workstations-only group ( 95 % CI=-74 , 7 minutes , p=0.285 ) . CONCLUSIONS A multi-component intervention was successful in reducing workplace sitting . These findings may have important practical and financial implication s for workplaces targeting sitting time reductions . CLINICAL TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry 00363297 Objective To investigate how and when changes in workplace sitting time occurred following a workplace intervention to inform evaluation of intervention success . Method The 4-week St and Up Comcare study ( June – September 2011 ) aim ed to reduce workplace sitting time via regularly interrupting and replacing sitting time throughout the day . Activity monitor ( activPAL3 ) workplace data from control ( n=22 ) and intervention participants ( n=21 ) were analysed . Differences in the number and usual duration of sitting bouts were used to evaluate how change occurred . To examine when change occurred , intervention effects were compared by hour since starting work and hour of the workday . Change in workplace activity ( sitting , st and ing , stepping ) was examined to further inform alignment with intervention messages . Individual variability was examined in how and when the change occurred . Results Overall , behavioural changes aligned with intervention aims . All intervention participants reduced total workplace sitting time , though there was wide individual variability observed ( range −29 to −262 min per 8 h workday ) . On average , intervention participants reduced number of sitting bouts ( −4.6 bouts ( 95 % CI −10.1 to 1.0 ) , p=0.106 ) and usual sitting bout duration ( −5.6 min ( 95 % CI −9.8 to −1.4 , p=0.011 ) ) relative to controls . Sitting time reductions were observed across the workday , though intervention effects varied by hour of the day ( p=0.015 ) . The intervention group successfully adopted the St and Up and Sit Less intervention messages across the day . Conclusion These analyses confirmed that this workplace intervention successfully modified sitting behaviour as intended ( ie , fewer and shorter sitting bouts , with changes occurring throughout the day ) OBJECTIVE To investigate the short-term efficacy of a multicomponent intervention to reduce office workers ' sitting time . METHODS Allocation for this non-r and omized controlled trial ( n=43 participants ; 56 % women ; 26 - 62 years ; Melbourne , Australia ) was by office floor , with data collected during July-September 2011 . The 4-week intervention emphasized three key messages : " St and Up , Sit Less , Move More " and comprised organizational , environmental , and individual elements . Changes in minutes/day at the workplace spent sitting ( primary outcome ) , in prolonged sitting ( sitting time accumulated in bouts ≥ 30 min ) , st and ing , and moving were objective ly measured ( activPAL3 ) . RESULTS Relative to the controls , the intervention group significantly reduced workplace sitting time ( mean change [ 95%CI ] : -125 [ -161 , -89 ] min/8-h workday ) , with changes primarily driven by a reduction in prolonged sitting time ( -73 [ -108 , -40 ] min/8-h workday ) . Workplace sitting was almost exclusively replaced by st and ing ( + 127 [ + 92 , + 162 ] min/8-h workday ) with non-significant changes to stepping time ( -2 [ -7 , + 4 ] min/8-h workday ) and number of steps ( -70 [ -350 , 210 ] ) . CONCLUSIONS This multicomponent workplace intervention demonstrated that substantial reductions in sitting time are achievable in an office setting . Larger studies with longer timeframes are needed to assess sustainability of these changes , as well as their potential longer-term impacts on health and work-related outcomes |
10,326 | 19,124,985 | Eccentric exercises have the most evidence of effectiveness in treatment of midportion Achilles tendinopathy . | OBJECTIVE The aim of this systematic review is to provide an easily accessible , clear summary of the best available evidence for nonoperative treatment of midportion Achilles tendinopathy . | AIM Despite the lateral epicondylitis or tennis elbow is a common cause of pain in orthopaedic and sports medicine , the results of the different modalities of conservative treatment are still contradictory . The pourpose of this study was to evaluate the efficacy of radial shock wave therapy ( RSWT ) in the treatment of tennis elbow . METHODS In a prospect i ve r and omized controlled single-blind study , of 75 eligible patients , 62 with tennis elbow were r and omly assigned to study group and control group . There were 31 patients in the study group and 31 patients in the control group . Both groups had received a treatment a week for 4 weeks ; the study group had received 2000 impulses of RSWT and the control group 20 impulses of RSWT . All patients were evaluated 3 times : before treatment , at the end of treatment and to 6 months follow-up . The evaluation consisted of assessment s of pain , pain-free grip strength test , and functional impairment . RESULTS Statistical analysis of visual analogue scale ( VAS ) , disabilities of the arm , shoulder , and h and ( DASH ) question naire and pain-free grip strength test scores has shown , both after treatment and to the follow-up at 6 months , significant difference comparing study group versus control group ( P < 0.001 ) . Statistical analysis within the groups , showed always statistically significant values for the study group . Also the control group showed statistically significant differences for some analyzed parameters . Nevertheless such differences result ed to be more statistics that not clinics as it showed the percentage of satisfied patients in the study group ( 87 % post-treatment ; 84 % follow-up ) in comparison with that of the control group ( 10 % post-treatment ; 3 % follow-up ) , and the number needed to treat ( NNT ) that is of 1.15 at post-treatment and of 1.25 to the 6 months follow-up . CONCLUSION The use of RSWT allowed a decrease of pain , and functional impairment , and an increase of the pain-free grip strength test , in patients with tennis elbow . The RSWT is safe and effective and must be considered as possible therapy for the treatment of patients with tennis elbow AIM Prognosis and treatment of Achilles tendon pain ( achillodynia ) has been insufficiently studied . The purpose of the present study was to examine the long-term effect of eccentric exercises compared with stretching exercises on patients with achillodynia . METHODS Patients with achillodynia for at least 3 months were r and omly allocated to one of two exercise regimens . Exercise was performed daily for a 3-month period . Symptom severity was evaluated by tendon tenderness , ultrasonography , a question naire on pain and other symptoms , and a global assessment of improvement . Follow-up was performed at time points 3 , 6 , 9 , 12 weeks and 1 year . RESULTS Of 53 patients with achillodynia 45 patients were r and omized to either eccentric exercises or stretching exercises . Symptoms gradually improved during the 1-year follow-up period and were significantly better assessed by pain and symptoms after 3 weeks and all later visits . However , no significant differences could be observed between the two groups . Women and patients with symptoms from the distal part of the tendon had significantly less improvement . CONCLUSIONS Marked improvement in symptoms and findings could be gradually observed in both groups during the 1-year follow-up period . To that extent this is due to effect of both regimens or the spontaneous improvement is unsettled Injuries involving the Achilles tendon and manifested as chronic tendon pain are common , especially among recreational athletes . In a pilot study on a small group of patients with chronic painful mid-portion Achilles tendinosis , eccentric calf-muscle training was shown to give good clinical results . The aim of this prospect i ve study was to investigate if the previously achieved good clinical results could be reproduced in a larger group of patients , and also to investigate the effects of eccentric calf-muscle training in patients with chronic insertional Achilles tendon pain . Seventy-eight consecutive patients , having chronic painful Achilles tendinosis at the mid-portion ( 2–6 cm level ) in a total of 101 tendons ( 55 unilateral and 23 bilateral ) , and thirty consecutive patients with chronic insertional Achilles tendon pain in 31 tendons ( 29 unilateral and one bilateral ) were treated with eccentric calf-muscle training for 12 weeks . Most patients were recreational athletes . Evaluation of the amount of tendon pain during activity was recorded on a visual analogue scale ( VAS ) , before and after treatment . In 90 of the 101 Achilles tendons ( 89 % ) with chronic painful mid-portion Achilles tendinosis , treatment was satisfactory and the patients were back on their pre-injury activity level after the 12-week training regimen . In these patients , the amount of pain during activity , registered on the VAS-scale ( mean±SD ) , decreased significantly from 66.8±19.4 to 10.2±13.7 . On the contrary , in only ten of the tendons ( 32 % ) with chronic insertional Achilles tendon pain was treatment satisfactory , with a significant decrease on the VAS-scale ( mean±SD ) , from 68.3±7.0 to 13.3±13.2 . Our conclusion is that treatment with eccentric calf-muscle training produced good clinical results in patients with chronic painful mid-portion Achilles tendinosis , but not in patients with chronic insertional Achilles tendon pain 70 consecutive adult , nonrheumatic patients with a painful achilles tendinopathy were r and omized to treatment with either a nonsteroid antiinflammatory drug ( piroxicam ) or placebo . Both groups received adjunct treatment with a period of rest combined with stretching and strengthening exercises . 52/70 cases were engaged in various sports , notably running . All subjects were evaluated on days 3 , 7 , 14 , and 28 with respect to pain , tenderness , swelling , ankle joint movement and muscle strength . Results were judged from residual symptoms and an overall assessment of the efficacy . No differences were seen between the groups at any time during the study . The overall result was identical with a rate of success slightly better than 50 percent which corresponds to the placebo response reported in other studies Achilles tendinopathy is common and treatment with eccentric exercises seems promising . We design ed a prospect i ve r and omized clinical trial to test the hypothesis that eccentric calf muscle exercises reduce pain and improve function in patients with Achilles tendinopathy . Forty-four patients were recruited from primary care ( mean age : 45 years ; 23 women ; 65 % active in sports ) and r and omized to three treatment groups for 12 weeks : eccentric exercises , a night splint or a combination of both treatments . Pain and function were evaluated at 6 , 12 , 26 and 52 weeks by the Foot and Ankle Outcome Score . At 6 weeks , the eccentric group reported a significant pain reduction ( 27 % compared with baseline , P = 0.007 ) which lasted for 1 year ( 42 % , P = 0.001 ) . The two groups treated with a night splint also reported significant but less pain reduction than the eccentric group . Differences between all the three groups were not significant . At 12 weeks , the eccentric group reported significantly less pain than the splint-only group ( P = 0.04 ) . More patients in the eccentric group than in the splint group returned to sport after 12 weeks . We conclude that eccentric exercises seem to reduce pain and improve function in patients with Achilles tendinopathy . Our results are in line with previous studies and strengthen the recommendation that patients should undergo an eccentric exercise program prior to considering other treatments such as surgery A double-blind , controlled study is presented on the effect of low-dosage heparin on acute calcaneal peritendinitis crepitans in young men . Treatment consisted in exemption from physical work and subcutaneous injection of heparin . 5000 I.U. , or placebo , once a day for 5 consecutive weekdays . During the first week the mean total symptom score showed a gradual fall to 32 and 34 % of the baseline values in the heparin ( n = 10 ) and the placebo group ( n = 10 ) , respectively . On day 15 the value was unchanged in the heparin group , whereas it had increased again to 45 % in the placebo group . However , the symptoms and signs recorded never differed significantly between the two groups . No adverse reactions were observed . Consequently , further studies are needed to show whether a treatment of acute peritendinitis can be obtained with heparin in a dosage with less risk of bleeding than that involved in the previously reported regimen A retrospective study is presented of 83 athletes with tendo Achillis pain ( TAP ) treated conservatively over a 12-year period from 1976 to 1988 . Local steroid injections did not contribute to an earlier return to sport , though many individuals were improved symptomatically . Local steroids were not found to have a deleterious effect on outcome . Steroids were used most frequently in the chronic cases that presented late and had been treated previously : this group had most recurrences and surgical intervention . One case of Achilles rupture ( 3 % ) occurred in the group treated with steroids . Early presentation for treatment led to an earlier return to sport and avoidance of recurrences . Recurrences were most frequent in athletes with bilateral Achilles tendinopathy . The tendo Achillis lesion may range from peritendinitis through a mixed lesion of the tendon and paratenon , to complete rupture . The management depends upon accurate diagnosis , its chronicity and the age and aspirations of the patient . Steroids are safe to use and further prospect i ve trials should note presentation time and disease staging accurately BACKGROUND Extracorporeal shock wave therapy ( ESWT ) is an increasingly popular therapeutic approach in the management of a number of tendinopathies . Benefit has been shown in calcific tendinitis of the rotator cuff , but evidence for its use in non-calcific disorders is limited . AIMS To perform a double blind r and omised controlled trial of moderate dose shock wave therapy in plantar fasciitis . METHODS Adults with plantar fasciitis for at least 3 months were r and omised to receive either active treatment ( 0.12 mJ/mm(2 ) ) or sham therapy , monthly for 3 months . Pain in the day , nocturnal pain and morning start-up pain were assessed at baseline , before each treatment and 1 and 3 months after completion of therapy . RESULTS Eighty-eight subjects participated and no differences existed between the groups at baseline . At 3 months , 37 % of the subjects in the ESWT group and 24 % in the sham group showed a positive response ( 50 % improvement from baseline ) with respect to pain . Positive responses in night pain occurred in 41 % and 31 % in the ESWT and sham groups , respectively . Positive responses in start-up pain occurred in 37 % and 36 % in the ESWT and sham groups , respectively . Both groups showed significant improvement over the course of the study , but no statistically significant difference existed between the groups with respect to the changes were seen in any of the outcome measures over the 6-month period . CONCLUSIONS There appears to be no treatment effect of moderate dose ESWT in subjects with plantar fasciitis . Efficacy may be highly dependent upon machine types and treatment protocol s. Further research is needed to develop evidence based recommendation for the use ESWT in musculoskeletal complaints Background : Low level laser therapy ( LLLT ) has gained increasing popularity in the management of tendinopathy and arthritis . Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action . Objective : To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon . Subjects : Seven patients with bilateral Achilles tendinitis ( 14 tendons ) who had aggravated symptoms produced by pain inducing activity immediately before the study . Method : Infrared ( 904 nm wavelength ) LLLT ( 5.4 J per point , power density 20 mW/cm2 ) and placebo LLLT ( 0 J ) were administered to both Achilles tendons in r and om blinded order . Results : Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 ( 95 % confidence interval 0.87 to 0.95 ) . Prostagl and in E2 concentrations were significantly reduced 75 , 90 , and 105 minutes after active LLLT compared with concentrations before treatment ( p = 0.026 ) and after placebo LLLT ( p = 0.009 ) . Pressure pain threshold had increased significantly ( p = 0.012 ) after active LLLT compared with placebo LLLT : the mean difference in the change between the groups was 0.40 kg/cm2 ( 95 % confidence interval 0.10 to 0.70 ) . Conclusion : LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis . LLLT may therefore have potential in the management of diseases with an inflammatory component In a previous uncontrolled pilot study we demonstrated very good clinical results with eccentric calf muscle training on patients with painful chronic Achilles tendinosis located at the 2–6 cm level in the tendon . In the present prospect i ve multicenter study ( Sundsvall and Umeå ) patients with painful chronic Achilles tendinosis at the 2–6 cm level in the tendon were r and omized to treatment with either an eccentric or a concentric training regimen for the calf muscles . The study included 44 patients , with 22 patients ( 12 men , 10 women ; mean age 48 years ) in each treatment group . The amount of pain during activity ( jogging or walking ) was recorded by the patients on a visual analogue scale , and patient satisfaction was assessed before and after treatment . The patients were instructed to perform their eccentric or concentric training regimen on a daily basis for 12 weeks . In both types of treatment regimen the patients were told to do their exercises despite experiencing pain or discomfort in the tendon during exercise . The results showed that after the eccentric training regimen 82 % of the patients ( 18/22 ) were satisfied and had resumed their previous activity level ( before injury ) , compared to 36 % of the patients ( 8/22 ) who were treated with the concentric training regimen . The results after treatment with eccentric training was significantly better ( P<0.002 ) than after concentric training . The good clinical results previously demonstrated in the pilot study with eccentric calf muscle training on patients with chronic Achilles tendinosis , were thus reproduced in this multicenter , showing superior results to treatment with concentric training Extracorporeal shockwave therapy ( ESWT ) has demonstrated efficacy in the treatment of recalcitrant proximal plantar fasciitis . The objective of this investigation was to compare the outcomes of participants treated with a new ESWT device with those treated with placebo . A total of 172 volunteer participants were r and omized in a 2:1 active-to-placebo ratio in this prospect i ve , double-blind , multicenter trial conducted between October 2003 and December 2004 . ESWT ( n=115 ) or placebo control ( n=57 ) was administered on a single occasion without local or systemic anesthesia or sedation , after which follow-up was undertaken . The primary outcomes were the blind assessor 's objective , and the participant 's subjective assessment s of heel pain during the first 3 months of follow-up . Participants were also followed up to 1 year to identify any adverse outcomes that may have been related to the shockwave device . On the visual analog scale , the blind assessor 's objective assessment of heel pain displayed a mean reduction of 2.51 in the shockwave group and 1.57 in the placebo group ; this difference was statistically significant ( P=.045 ) . On the visual analog scale , the participant 's self- assessment of heel pain displayed a mean reduction of 3.39 in the shockwave group and 1.78 in the placebo group ; this difference was statistically significant ( P<.001 ) . No serious adverse events were observed at any time . It was concluded that ESWT was both efficacious and safe for participants with chronic proximal plantar fasciitis that had been unresponsive to exhaustive conservative treatment In a prospect i ve study over the two years 1981 - 1982 , there were 1186 separate sporting injuries treated at a Sports Injury Clinic . Just over 75 % of patients were aged between 16 and 25 years old , while 80 % were male . Football , Rugby , Running , Squash and Rowing contributed over 70 % of these injuries . The commonest injuries were to the lower limb and lumbar region . In 43 % of knee injuries there was strain of the collateral ligaments , while another 26 % had patello-femoral pain . Short distance running was associated with an increase in shin splints , tibial stress fractures and hamstring injuries . Long distance running was associated with an increase in ankle and foot injuries . Sports Injury Clinics can benefit the injured athlete and there appears to be a need for their development in major hospitals BACKGROUND The use of extracorporeal shock wave therapy for the treatment of lateral epicondylitis is controversial . The purpose of this study was to evaluate the use of extracorporeal shock wave therapy without local anesthesia to treat chronic lateral epicondylitis . METHODS One hundred and fourteen patients with a minimum six-month history of lateral epicondylitis that was unresponsive to conventional therapy were r and omized into double-blind active treatment and placebo groups . The protocol consisted of three weekly treatments of either low-dose shock wave therapy without anesthetic or a sham treatment . Patients had a physical examination , including provocation testing and dynamometry , at one , four , eight , and twelve weeks and at six and twelve months after treatment . Radiographs , laboratory studies , and electrocardiograms were also evaluated prior to participation and at twelve weeks . A visual analog scale was used to evaluate pain , and an upper extremity functional scale was used to assess function . Crossover to active treatment was initiated for nonresponsive patients who had received the placebo and met the inclusion criteria after twelve weeks . RESULTS A total of 108 of the 114 r and omized patients completed all treatments and the twelve weeks of follow-up required by the protocol . Sixty-one patients completed one year of follow-up , whereas thirty-four patients crossed over to receive active treatment . A significant difference ( p = 0.001 ) in pain reduction was observed at twelve weeks in the intent-to-treat cohort , with an improvement in the pain score of at least 50 % seen in 61 % ( thirty-four ) of the fifty-six patients in the active treatment group who were treated according to protocol compared with 29 % ( seventeen ) of the fifty-eight subjects in the placebo group . This improvement persisted in those followed to one year . Functional activity scores , activity-specific evaluation , and the overall impression of the disease state all showed significant improvement as well ( p < 0.05 ) . Crossover patients also showed significant improvement after twelve weeks of active treatment , with 56 % ( nineteen of thirty-four ) achieving an improvement in the pain score of at least 50 % ( p < 0.0001 ) . CONCLUSIONS These results demonstrate that low-dose shock wave therapy without anesthetic is a safe and effective treatment for chronic lateral epicondylitis Objective : To prospect ively investigate tendon thickness and tendon structure by ultrasonography in patients treated with eccentric calf muscle training for painful chronic Achilles tendinosis located at the 2–6 cm level in the tendon . Methods : The patients were examined with grey scale ultrasonography before and 3.8 years ( mean ) after the 12 week eccentric training regimen . At follow up , a question naire assessed present activity level and satisfaction with treatment . Results : Twenty six tendons in twenty five patients ( 19 men and six women ) with a mean age of 50 years were followed for a mean of 3.8 years ( range 1.6–7.75 ) . All patients had a long duration of painful symptoms ( mean 17.1 months ) from chronic Achilles tendinosis before treatment . At follow up , 22 of 25 patients were satisfied with treatment and active in Achilles tendon loading activities at the desired level . Ultrasonography showed that tendon thickness ( at the widest part ) had decreased significantly ( p<0.005 ) after treatment ( 7.6 ( 2.3 ) v 8.8 ( 3 ) mm ; mean ( SD ) ) . In untreated normal tendons , there was no significant difference in thickness after treatment ( 5.3 ( 1.3 ) mm before and 5.9 ( 0.8 ) mm after ) . All tendons with tendinosis had structural abnormalities ( hypoechoic areas and irregular structure ) before the start of treatment . After treatment , the structure was normal in 19 of the 26 tendons . Six of the seven patients with remaining structural abnormalities experienced pain in the tendon during loading . Conclusions : Ultrasonographic follow up of patients with mid-portion painful chronic Achilles tendinosis treated with eccentric calf muscle training showed a localised decrease in tendon thickness and a normalised tendon structure in most patients . Remaining structural tendon abnormalities seemed to be associated with residual pain in the tendon Background Aprotinin , a serine proteinase inhibitor , reduces bleeding during cardiac surgery . As aprotinin is derived from bovine lung , it has antigenic properties . This investigation examined the incidence of anaphylactic reactions in patients reexposed to aprotinin and the relation to preformed antiaprotinin immunoglobulin (Ig)G and IgE antibodies . Methods This prospect i ve observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to aprotinin between 1995 and 1996 . Antiaprotinin IgG and IgE antibody measurements , using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay , respectively , were performed preoperatively and postoperatively . An anaphylactic reaction was defined as major changes from baseline within 10 min of aprotinin administration of systolic pressure 20 % or greater , heart rate 20 % or greater , inspiratory pressure greater than 5 cm H2O , or a skin reaction . Results In 121 cases ( 71 adults , 46 children ) , a mean aprotinin reexposure interval of 1,654 days ( range , 16–7,136 days ) was observed . Preoperative antiaprotinin IgG ( optical density ratio > 3 ) and IgE antibodies ( radioallergosorbent test [ RAST ] score < 3 ) were detected in 18 and 9 patients , respectively . High concentrations of each ( IgG , optical density ratio > 10 ; IgE , RAST score ≥ 3 ) were detected in five patients . Three patients ( 2.5 % ; 95 % confidence interval , 0.51–7.1 % ) experienced an anaphylactic reaction after aprotinin exposure , followed by full recovery ; these patients had reexposure intervals less than 6 months ( 22 , 25 , and 25 days ) and the highest preoperative IgG concentrations of all patients ( P < 0.05 ) . Assay sensitivity was 100 % , as no anaphylactic reactions occurred in IgG-negative patients ( 95 % confidence interval , 0.0–3.1 % ) ; assay specificity was 98 % . Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients . Conclusions Quantitative detection of antiaprotinin IgE and IgG lacks specificity for predictive purpose s ; however , quantitation of antiaprotinin IgG may identify patients at risk for developing an anaphylactic reaction to aprotinin reexposure Background Achilles tendinopathy is a common overuse injury , especially among athletes involved in activities that include running and jumping . Often an initial period of rest from the pain-provoking activity is recommended . Purpose To prospect ively evaluate if continued running and jumping during treatment with an Achilles tendon-loading strengthening program has an effect on the outcome . Study Design R and omized clinical control trial ; Level of evidence , 1 . Methods Thirty-eight patients with Achilles tendinopathy were r and omly allocated to 2 different treatment groups . The exercise training group ( n = 19 ) was allowed , with the use of a pain-monitoring model , to continue Achilles tendon-loading activity , such as running and jumping , whereas the active rest group ( n = 19 ) had to stop such activities during the first 6 weeks . All patients were rehabilitated according to an identical rehabilitation program . The primary outcome measures were the Swedish version of the Victorian Institute of Sports Assessment —Achilles question naire ( VISA-A-S ) and the pain level during tendon-loading activity . Results No significant differences in the rate of improvements were found between the groups . Both groups showed , however , significant ( P < .01 ) improvements , compared with baseline , on the primary outcome measure at all the evaluations . The exercise training group had a mean ( st and ard deviation ) VISA-A-S score of 57 ( 15.8 ) at baseline and 85 ( 12.7 ) at the 12-month follow-up ( P < .01 ) . The active rest group had a mean ( st and ard deviation ) VISA-A-S score of 57 ( 15.7 ) at baseline and 91 ( 8.2 ) at the 12-month follow-up ( P < .01 ) . Conclusions No negative effects could be demonstrated from continuing Achilles tendon-loading activity , such as running and jumping , with the use of a pain-monitoring model , during treatment . Our treatment protocol for patients with Achilles tendinopathy , which gradually increases the load on the Achilles tendon and calf muscle , demonstrated significant improvements . A training regimen of continued , pain-monitored , tendon-loading physical activity might therefore represent a valuable option for patients with Achilles tendinopathy A prospect i ve , r and omised , double-blind study of 28 patients presenting with Achilles paratendonitis was undertaken in order to evaluate the role of peritendonous injection of methy prednisolone acetate ( Depo Medrone ) . At presentation patients were either administered peri-tendonous injection of 40 mgs of methyl prednisolone acetate suspended in 1 ml of 0.25 % marcaine or 2 ml of 0.25 % marcaine alone . Response was gauged by resolution of pain , tenderness and return to normal activity . Patients who failed to respond to initial treatment were crossed over to the other group at 12 weeks . All patients received st and ardised physiotherapy . Results indicate that peri-tendonous injection of methyl prednisolone acetate is of no value in Achilles paratendonitis CONTEXT Extracorporeal shock wave therapy ( ESWT ) is increasingly used for plantar fasciitis , but limited evidence supports its use . OBJECTIVE To determine whether ultrasound-guided ESWT reduces pain and improves function in patients with plantar fasciitis . DESIGN Double-blind , r and omized , placebo-controlled trial conducted between April 1999 and June 2001 . SETTING Participants were recruited from the community-based referring physicians ( primary care physicians , rheumatologists , orthopedic surgeons , and sports physicians ) of a radiology group in Melbourne , Australia . PARTICIPANTS We screened 178 patients and enrolled 166 ; 160 completed the 15-week protocol . Entry criteria included age at least 18 years with plantar fasciitis , defined as heel pain maximal over the plantar aspect of the foot of at least 6 weeks ' duration , and an ultrasound-confirmed lesion , defined as thickening of the origin of the plantar fascia of at least 4 mm , hypoechogenicity , and alterations in the normal fibrillary pattern . INTERVENTIONS Patients were r and omly assigned to receive either ultrasound-guided ESWT given weekly for 3 weeks to a total dose of at least 1000 mJ/mm(2 ) ( n = 81 ) , or identical placebo to a total dose of 6.0 mJ/mm(2 ) ( n = 85 ) . MAIN OUTCOME MEASURES Overall , morning , and activity pain , measured on a visual analog scale ; Maryl and Foot Score ; walking ability ; Short-Form-36 Health Survey ( SF-36 ) score ; and Problem Elicitation Technique score , measured at 6 and 12 weeks after treatment completion . RESULTS At 6 and 12 weeks , there were significant improvements in overall pain in both the active group and placebo group ( mean [ SD ] improvement , 18.1 [ 30.6 ] and 19.8 [ 33.7 ] at 6 weeks [ P = .74 for between-group difference ] , and 26.3 [ 34.8 ] and 25.7 [ 34.9 ] at 12 weeks [ P = .99 ] , respectively ) . Similar improvements in both groups were also observed for morning and activity pain , walking ability , Maryl and Foot Score , Problem Elicitation Technique , and SF-36 . There were no statistically significant differences in the degree of improvement between treatment groups for any measured outcomes . CONCLUSION We found no evidence to support a beneficial effect on pain , function , and quality of life of ultrasound-guided ESWT over placebo in patients with ultrasound-proven plantar fasciitis 6 and 12 weeks following treatment Background : Although the application of low-energy extracorporeal shock waves to treat musculoskeletal disorders is controversial , there has been some limited , short-term evidence of its effectiveness for the treatment of chronic plantar fasciitis . Methods : From 1993 to 1995 , a prospect i ve , two-tailed , r and omized , controlled , observer-blinded pilot trial was performed to assess whether three applications of 1000 impulses of low-energy shock waves ( Group I ) led to a superior clinical outcome when compared with three applications of ten impulses of low-energy shock waves ( Group II ) in patients with intractable plantar heel pain . The sample size was 112 . The main outcome measure was patient satisfaction according to a four-step score ( excellent , good , acceptable , and poor ) at six months . Secondary outcome measures were patient satisfaction according to the four-step score at five years and the severity of pain on manual pressure , at night , and at rest as well as the ability to walk without pain at six months and five years . Results : At six months , the rate of good and excellent outcomes according to the four-step score was significantly ( 47 % ) better ( p < 0.0001 ) in Group I than in Group II . As assessed on a visual analog scale , the score for pain caused by manual pressure at six months had decreased to 19 points , from 77 points before treatment , in Group I , whereas in Group II the ratings before treatment and at six months were 79 and 77 points ( p < 0.0001 for the difference between groups ) . In Group I , twenty-five of forty-nine patients were able to walk completely without pain at six months compared with zero of forty-eight patients in Group II ( p < 0.0001 ) . By five years , the difference in the rates of good and excellent outcomes according to the four-step score was only 11 % in favor of Group I ( p = 0.071 ) because of a high rate of good and excellent results from subsequent surgery in Group II ; the score for pain caused by manual pressure had decreased to 9 points in Group I and to 29 points in Group II ( p = 0.0006 for the difference between groups ) . At five years , five ( 13 % ) of thirty-eight patients in Group I had undergone an operation of the heel compared with twenty-three ( 58 % ) of forty patients in Group II ( p < 0.0001 ) . Conclusions : Three treatments with 1000 impulses of low-energy shock waves appear to be an effective therapy for plantar fasciitis and may help the patient to avoid surgery for recalcitrant heel pain . In contrast , three applications of ten impulses did not improve symptoms substantially The purpose of this double-blind study was to evaluate the effects of iontophoresis with dexamethazone to iontophoresis with saline solution on patients who had acute ( less than 3 months ) pain from the Achilles tendon , in terms of range of motion , muscular endurance , pain and symptoms . Twenty-five patients ( 15 men and 10 women ) , aged between 18 and 76 years ( mean=38 ) , were evaluated before and after 2 weeks of treatment with iontophoresis , as well as after 6 weeks , 3 and 6 months and 1 year . Two groups were treated for 2 weeks with iontophoresis for each treatment . Three ml of dexamethazone were used for the experiment group ( n=14 ) and 3 ml of saline solution for the control group ( n=11 ) . Both groups then followed the same rehabilitation programme for 10 weeks . Good reliability was found for the toe-raise and range of motion tests . Poor reliability was , however , found for the pain on palpation test , which was therefore excluded . No difference was found between or within groups for the toe-raise test . Several significant improvements were seen in the experiment group but not in the control group , in the range of motion test , pain during and after physical activity , pain during walking and walking up and down stairs , morning stiffness and tendon swelling . Even though the small sample size limits the possibilities to draw definite conclusions , we conclude from the present study , using a double-blind , r and omised approach and a 1-year follow-up period , that positive effects from using iontophoresis with dexamethazone were found in the treatment of patients with acute Achilles tendon pain Background Extracorporeal shockwave treatment has shown mixed short-term results for plantar fasciitis . However , the long-term results are not available . Hypothesis Long-term results of shockwave treatment are comparable with short-term results . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods This prospect i ve study consisted of 149 patients ( 168 heels ) with an established diagnosis of chronic plantar fasciitis , including 79 patients ( 85 heels ) in the shockwave treatment group and 70 patients ( 83 heels ) in the control group . In the shockwave group , patients received 1500 impulses of shockwaves at 16 kV to the affected heel in a single session . Patients in the control group received conservative treatment consisting of nonsteroidal anti-inflammatory drugs , orthotics , physical therapy , an exercise program , and /or a local cortisone injection . Patients were evaluated at 60 to 72 months ( shockwave group ) or 34 to 64 months ( control group ) with a 100-point scoring system including 70 points for pain and 30 points for function . The clinical outcomes were rated as excellent , good , fair , or poor . Results Before treatment , the groups showed no significant differences in the scores for pain and function . After treatment , the shockwave group showed significantly better pain and function scores as compared with the control group . The overall results were 69.1 % excellent , 13.6 % good , 6.2 % fair , and 11.1 % poor for the shockwave group ; and 0 % excellent , 55 % good , 36 % fair , and 9 % poor for the control group ( P < .001 ) . The recurrence rate was 11 % ( 9/81 heels ) for the shockwave group versus 55 % ( 43/78 heels ) for the control group ( P < .001 ) . There were no systemic or local complications or device-related problems . Conclusion Extracorporeal shockwave treatment is effective and safe for patients with plantar fasciitis , with good long-term results Despite numerous publications and clinical trials , the results of treatment of recalcitrant chronic plantar fasciitis with extracorporeal shockwave therapy ( ESWT ) still remain equivocal as to whether or not this treatment provides relief from the pain associated with this condition . The objective of this study was to determine whether extracorporeal shock wave therapy can safely and effectively relieve the pain associated with chronic plantar fasciitis compared to placebo treatment , as demonstrated by pain with walking in the morning . This was set in a multicenter , r and omized , placebo-controlled , double-blind , confirmatory clinical study undertaken in four outpatient orthopedic clinics . The patients , 114 adult subjects with chronic plantar fasciitis , recalcitrant to conservative therapies for at least 6 months , were r and omized to two groups . Treatment consisted of approximately 3,800 total shock waves ( + /-10 ) reaching an approximated total energy delivery of 1,300 mJ/mm(2 ) ( ED+ ) in a single session versus placebo treatment . This study demonstrated a statistically significant difference between treatment groups in the change from baseline to 3 months in the primary efficacy outcome of pain during the first few minutes of walking measured by a visual analog scale . There was also a statistically significant difference between treatments in the number of participants whose changes in Visual Analog Scale scores met the study definition of success at both 6 weeks and 3 months posttreatment ; and between treatment groups in the change from baseline to 3 months posttreatment in the Roles and Maudsley Score . The results of this study confirm that ESWT administered with the Dornier Epos Ultra is a safe and effective treatment for recalcitrant plantar fasciitis Background : Achilles tendinopathy is a common condition , which can become chronic and interfere with athletic performance . The proteinase inhibitor aprotinin ( as injection ) has been found to improve recovery in patellar tendinopathy1 ( evidence level 1b2 ) and Achilles tendinopathy.3 Internationally this therapy is being used based on this limited knowledge base . Aim : To evaluate whether aprotinin injections decrease time to recovery in Achilles tendinopathy . Method : A prospect i ve , r and omised , double blind , placebo controlled trial was performed comparing saline ( 0.9 % ) plus local anaesthetic injections and eccentric exercises with aprotinin ( 30 000 kIU ) plus local anaesthetic injection and eccentric exercise . Three injections were given , each a week apart . In total , 26 patients , with 33 affected tendons , were enrolled for this study . Results : At no follow up point ( 2 , 4 , 12 , or 52 weeks ) was there any statistically significant difference between the treatment group and placebo . This included VISA-A scores4 and secondary outcome measures . However , a trend for improvement over placebo was noted . Conclusion : In this study on Achilles tendinopathy , aprotinin was not shown to offer any statistically significant benefit over placebo . Larger multicentre trials are needed to evaluate the efficacy of aprotinin in Achilles tendinopathy Local injections of the sclerosing substance Polidocanol has been demonstrated to give good clinical results in a pilot study on patients with chronic Achilles tendinopathy . In this study , 20 consecutive patients ( 9 men and 11 women , mean age 50 years ) with chronic painful mid-portion Achilles tendinopathy were r and omised to injection treatment with either Polidocanol ( 5 mg/ml ) ( group A ) or Lidocaine hydro-chloride ( 5 mg/ml ) + Adrenaline ( 5 μg/ml ) ( group B ) . Both substances have a local anaesthetic effect , but Polidocanol also has a sclerosing effect . The patients and the treating physician were blinded to the substance injected . The short-term effects were evaluated after a maximum of two treatments , 3–6 weeks apart . Before treatment , all patients had structural tendon changes and neo-vascularisation demonstrated with US and colour doppler . Under US and colour doppler-guidance , the injections targeted the area of neo-vascularisation just outside the ventral part of the tendon . For evaluation , the patients recorded the severity of Achilles tendon pain during tendon loading activity , before and after treatment , on a VAS . Patient ’s satisfaction with treatment was also assessed . At follow-up ( mean 3 months ) after a maximum of two treatments , 5/10 patients in group A were satisfied with the treatment and had a significantly reduced level of tendon pain ( p<0.005 ) . In group B , no patient was satisfied with treatment . In the pain-free tendons , but not in the painful tendons , neo-vascularisation was absent after treatment . After completion of the study , treatment with Polidocanol injections ( Cross-over in group B and additional treatments in group A ) result ed in 10/10 and 9/10 satisfied patients in group A and B , respectively . In summary , injections with the sclerosing substance Polidocanol have the potential to reduce tendon pain during activity in patients with chronic painful mid-portion Achilles tendinopathy Background : On the basis of observational trials , numerous investigators have recommended extracorporeal shock wave therapy as an alternative treatment for chronic lateral epicondylitis of the elbow . However , there has been no evidence of its efficacy from well- design ed r and omized clinical trials . The objective of this study was to find out whether extracorporeal shock wave therapy in combination with local anesthesia was superior to placebo therapy in combination with local anesthesia . Methods : A r and omized multicenter trial with a parallel-group design was conducted . Following administration of local anesthesia , either extracorporeal shock wave therapy with three treatments of 2000 pulses each and a positive energy flux density ( ED+ ) of 0.07 to 0.09 mJ/mm 2 or placebo therapy was applied on an outpatient basis . Treatment allocation was blinded for patients and for observers . The primary end point was based on the rate of success , as determined with the Roles and Maudsley score and whether additional treatment was required , twelve weeks after the intervention . Crossover was possible after assessment of the primary end point . Secondary end points were the Roles and Maudsley score , subjective pain rating , and grip strength after six and twelve weeks and after twelve months . The planned number of 272 patients was included in the study . Results : The primary end point could be assessed for 90.8 % of the patients . The success rate was 25.8 % in the group treated with extracorporeal shock wave therapy and 25.4 % in the placebo group , a difference of 0.4 % with a 95 % confidence interval of -10.5 % to 11.3 % . Similarly , there was no relevant difference between groups with regard to the secondary end points . Improvement was observed in two-thirds of the patients from both groups twelve months after the intervention . Few side effects were reported . Conclusions : Extracorporeal shock wave therapy as applied in the present study was ineffective in the treatment of lateral epicondylitis . The previously reported success of this therapy appears to be attributable to inappropriate study design s. Different application protocol s might improve clinical outcome . We recommend that extracorporeal shock wave therapy be applied only in high- quality clinical trials until it is proved to be effective AIM Efficacy of low-energy shock wave therapy for recalcitrant plantar fasciitis . METHOD 32 patients were r and omly assigned into real and placebo ESWT groups , treatment comprised 1000 impulses of 0,08 mJ/mm 2 at 14 kV ( OssaTron OSA 120 , HMT AG , Switzerl and ) in 12 cases repeated after six weeks or placebo ( energy-absorbing foil ) . Follow-up evaluation ( 19 , 32 and 48 wks . ) included specific question naire , clinical -functional examination and measurement of plantar pressure while walking ( Emed AT-4 . pedograph , Novel GmbH , Munich ) . Examiner and patients were blinded . RESULTS 88 % of the treatment group were pain free or had good results . None of the placebo group were pain free , 33.3 % had good results ( Roles and Maudsley Score ) . The treatment group showed significantly better outcome for morning and resting pain , pressure stamp-tolerance and walking ability . Pedography did not show a clear correlation between pain relief and load pattern . CONCLUSION The results of this study corroborate the value of ESWT for recalcitrant plantar fascitis . As a non invasive technique with low side effects , it can complement the row of conservative treatments The purpose was to examine the reliability of measurement techniques and evaluate the effect of a treatment protocol including eccentric overload for patients with chronic pain from the Achilles tendon . Thirty-two patients with proximal achillodynia ( 44 involved Achilles tendons ) participated in tests for reliability measures . No significant differences and strong ( r=0.56 - 0.72 ) or very strong ( r=0.90 - 0.93 ) correlations were found between pre-tests , except for the documentation of pain at rest ( P<0.008 , r=0.45 ) . To evaluate the effect of a 12-week treatment protocol for patients with chronic proximal achillodynia ( pain longer than three months ) 40 patients ( 57 involved Achilles tendons ) with a mean age of 45 years ( range 19 - 77 ) were r and omised into an experiment group ( n=22 ) and a control group ( n=18 ) . Evaluations were performed after six weeks of treatment and after three and six months . The evaluations ( including the pre-tests ) , performed by a physical therapist unaware of the group the patients belonged to , consisted of a question naire , a range of motion test , a jumping test , a toe-raise test , a pain on palpation test and pain evaluation during jumping , toe-raises and at rest . A follow-up was also performed after one year . There were no significant differences between groups at any of the evaluations , except that the experiment group jumped significantly lower than the control group at the six-week evaluation . There was , however , an overall better result for the experiment group with significant improvements in plantar flexion , and reduction in pain on palpation , number of patients having pain during walking , having periods when asymptomatic and having swollen Achilles tendon . The controls did not show such changes . Furthermore , at the one-year follow-up there were significantly more patients in the experiment group , compared with the control group , that were satisfied with their present physical activity level , considered themselves fully recovered , and had no pain during or after physical activity . The measurement techniques and the treatment protocol with eccentric overload used in the present study can be recommended for patients with chronic pain from the Achilles tendon Thirty-three subjects entered a blind-observer , r and om , prospect i ve study of three forms of conservative treat ment of sports-induced Achilles tendinitis , results being assessed by clinical and biomechanical parameters . Two patient groups received heel pads , ultrasound , and exercises , while the third received only ultrasound and exercises . All three groups showed some improve ment at both 10 day and 2 month assessment , but the cl aim ed benefit of viscoelastic pads widely used by athletes was not substantiated . The more striking bene fit from ultrasound and exercises alone occurred in patients with a shorter history ; a comparison of duration of injury in all three groups suggested this was an important factor influencing outcome . The study has highlighted the need for biomechanical outcome measures as well as for more objective clinical outcome measures in the assessment of physical ther apy Aim : To assess whether the use of a night splint is of added benefit on functional outcome in treating chronic midportion Achilles tendinopathy . Methods : This was a single-blind , prospect i ve , single centre , r and omised controlled trial set in the Sports Medical Department , The Hague Medical Centre , The Netherl and s. Inclusion criteria were : age 18–70 years , active participation in sports , and tendon pain localised at 2–7 cm from distal insertion . Exclusion criteria were : insertional disorders , partial or complete ruptures , or systemic illness . 70 tendons were included and r and omised into one of two treatment groups : eccentric exercises with a night splint ( night splint group , n = 36 ) or eccentric exercises only ( eccentric group , n = 34 ) . Interventions : Both groups completed a 12-week heavy-load eccentric training programme . One group received a night splint in addition to eccentric exercises . At baseline and follow-up at 12 weeks , patient satisfaction , Victorian Institute of Sport Assessment –Achilles question naire ( VISA-A ) score and reported compliance were recorded by a single-blind trained research er who was blinded to the treatment . Results : After 12 weeks , patient satisfaction in the eccentric group was 63 % compared with 48 % in the night splint group . The VISA-A score significantly improved in both groups ; in the eccentric group from 50.1 to 68.8 ( p = 0.001 ) and in the night splint group from 49.4 to 67.0 ( p<0.001 ) . There was no significant difference between the two groups in VISA-A score ( p = 0.815 ) and patient satisfaction ( p = 0.261 ) . Conclusion : A night splint is not beneficial in addition to eccentric exercises in the treatment of chronic midportion Achilles tendinopathy Background : The diagnosis of Achilles and patella tendinitis has until recently been based on clinical examination , and treatment with local steroid injection has been given blindly . This is the first r and omized , double blind , placebo‐controlled study of local steroid injection in athletes with chronic tendinitis , which used ultrasonography to increase diagnostic accuracy , to guide the correct placement of local steroid and , conjunctively with pressure algometry , to objectify and monitor the results of treatment . Method : Forty‐eight athletes each with severe symptomatic tendinitis of a patellar ( 24 ) or Achilles tendon ( 24 ) for more than 6 months , whose conditions were confirmed ultrasonographically , and who all failed conservative treatment ( rehabilitation ) were included in this double‐blind , placebo‐controlled study and treated with three ultrasonographically guided peritendinous injections of steroid or placebo . Results : The conditions of only one‐third of the referred athletes with clinical ly suspected tendinitis were confirmed by ultrasonographic examination . The ultrasonographically guided peritendinous injection of steroid had a significant effect in reducing pain and thickening of tendons . Conclusion : Ultrasonography should be used in the future to assure precise diagnosis and to guide the peritendinous injection of steroid in chronic Achilles and patella tendinitis . Ultrasonography and pressure algometry are recommended as objective methods for monitoring the effect of treatment . Ultrasonographically guided injection of long‐acting steroid can normalize the ultrasonographic pathological lesions in the Achilles and patellar tendons , and has a dramatic clinical effect but when combined with aggressive rehabilitation with running after a few days , many will have relapse of symptoms within 6 months In this double-blind trial in 60 recreational athletes suffering from Achilles peritendinitis , we compared the effect of local injections of glycosaminoglycan polysulfate ( GAGPS ) with oral indomethacin ( IM ) administered over a 2-week period . Orthotic devices were prescribed in 66 % of the cases to control biomechanical errors . The results after 1-year follow-up showed that GAGPS had a good overall therapeutic effect on two-thirds of the patients compared to one-third of the IM treated . In the patients with symptoms lasting longer than 3 months , IM had an effect in only 12 % while GAGPS was beneficial in 59 % . Twenty-five cases of non-responders and relapses underwent a crossover treatment . Those who received IM in this second period did not benefit from this treatment while those who received GAGPS showed a moderate to good effect in 8/17 ( 47 % ) after a 2-week follow-up . A different mode of action is suggested as an explanation of the encouraging results The aim of this study was to compare the effect of extracorporeal shockwave therapy ( ESWT ) in patients with chronically painful proximal plantar fasciitis with a conventional conservative treatment consisting of nonsteroidal anti-inflammatory drugs , heel cup , orthoses and /or shoe modifications , local steroid injections and electrotherapy . Forty-seven patients ( 49 feet ) with a previously unsuccessful conservative treatment of at least six months were r and omized to two groups . Treatment of Group 1 ( 25 heels ) started immediately with three sessions of ESWT ( 3000 shockwaves/session of 0.2 mJ/mm2 ) at weekly intervals . In the patients of Group 2 ( 24 heels ) treatment was continued for 12 weeks . After this period they were treated using the protocol of Group 1 . No significant difference of pain and walking time after further non-ESWT treatment ( three months ) was seen . Six months after ESWT pain decreased by 64 % to 88 % on the visual analog scale ( VAS ) and the comfortable walking time had increased significantly in both groups Background Few r and omized controlled trials compare different methods of management in chronic tendinopathy of the main body of tendo Achillis . Purpose To compare the effectiveness of 3 management strategies — group 1 , eccentric loading ; group 2 , repetitive low-energy shock-wave therapy ( SWT ) ; and group 3 , wait and see — in patients with chronic tendinopathy of the main body of tendo Achillis . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Seventy-five patients with a chronic recalcitrant ( > 6 months ) noninsertional Achilles tendinopathy were enrolled in a r and omized controlled study . All patients had received unsuccessful management for > 3 months , including at least ( 1 ) peritendinous local injections , ( 2 ) nonsteroidal anti-inflammatory drugs , and ( 3 ) physiotherapy . A computerized r and om-number generator was used to draw up an allocation schedule . Analysis was on intention-to-treat basis . Results At 4 months from baseline , the Victorian Institute of Sport Assessment (VISA)-A score increased in all groups , from 51 to 76 points in group 1 ( eccentric loading ) , from 50 to 70 points in group 2 ( repetitive low-energy SWT ) , and from 48 to 55 points in group 3 ( wait and see ) . Pain rating decreased in all groups , from 7 to 4 points in group 1 , from 7 to 4 points in group 2 , and from 8 to 6 points in group 3 . Fifteen of 25 patients in group 1 ( 60 % ) , 13 of 25 patients in group 2 ( 52 % ) , and 6 of 25 patients in Group 3 ( 24 % ) reported a Likert scale of 1 or 2 points ( “ completely recovered ” or “ much improved ” ) . For all outcome measures , groups 1 and 2 did not differ significantly . For all outcome measures , groups 1 and 2 showed significantly better results than group 3 . Conclusion At 4-month follow-up , eccentric loading and low-energy SWT showed comparable results . The wait- and -see strategy was ineffective for the management of chronic recalcitrant tendinopathy of the main body of the Achilles tendon |
10,327 | 30,707,329 | Text message reminder interventions were most successful in increasing rates of frequent HIV testing .
Las intervenciones us and o recordatorios por mensajes de texto fueron más exitosas en incrementar las tasas de realizarse pruebas frecuentes . | As of 2017 , the Centers for Disease Control and Prevention ( CDC ) HIV testing guidelines recommend that those at increased risk for HIV are tested two to four times per year .
Evidence -based interventions that promote frequent and repeated testing remain sparse .
We conducted a systematic review to : ( 1 ) identify frequent testing interventions ; and ( 2 ) determine which were successful in increasing frequent testing rates . | Background Patients at increased risk of sexually transmitted infections (STIs)/HIV acquisition are advised to reattend for retesting . A previous study showed that ‘ generic ’ text reminders did not improve reattendance . Aim To assess if a personalised text message with increased contact information would increase reattendance rates of at-risk patients . Methods Patients who are at risk of future STIs , defined by having a current acute STI , attending for emergency contraception , commercial sex workers ( CSWs ) or men who have sex with men ( MSM ) , were sent a text reminder to reattend for retesting 6 weeks after initial visit . Reattendance rates were measured for September to December 2012 ( control group who received a generic text message ) and February to May 2014 ( intervention ‘ personalised message ’ group who received a text message containing their first name and ways to contact the clinic ) . Reattendance was counted within 4 months of the end of the initial episode of care . Results The reattendance rate was significantly higher for the intervention group : 149/266 ( 56 % ) than the control group : 90/273 ( 33 % ) ( p=0.0001 ) and was also significantly higher in the intervention group than the control group in patients with the following risks : recent chlamydia ( 64/123 ( 52 % ) vs 43/121 ( 36 % ) ) ( p=0.03 ) , recent gonorrhoea ( 41/64 ( 64 % ) vs 4/21 ( 19 % ) ) ( p=0.0003 ) and MSM ( 26/45 ( 58 % ) vs 3/18 ( 16 % ) ) ( p=0.006 ) . New STI rates in the reattending intervention group and controls were 26/ 149 ( 17 % ) and 13/90 ( 14 % ) ( n.s ) , respectively . Conclusions Sending a personalised text message with increased contact information as a reminder for retesting increased reattendance rates by 23 % in patients who are at higher risk of STIs BACKGROUND Frequent testing of individuals at high risk of HIV is central to current prevention strategies . We aim ed to determine if HIV self-testing would increase frequency of testing in high-risk gay and bisexual men , with a particular focus on men who delayed testing or had never been tested before . METHODS In this r and omised trial , HIV-negative high-risk gay and bisexual men who reported condomless anal intercourse or more than five male sexual partners in the past 3 months were recruited at three clinical and two community-based sites in Australia . Enrolled participants were r and omly assigned ( 1:1 ) to the intervention ( free HIV self-testing plus facility-based testing ) or st and ard care ( facility-based testing only ) . Participants completed a brief online question naire every 3 months , which collected the number of self-tests used and the number and location of facility-based tests , and HIV testing was subsequently source d from clinical records . The primary outcome of number of HIV tests over 12 months was assessed overall and in two strata : recent ( last test ≤2 years ago ) and non-recent ( > 2 years ago or never tested ) testers . A statistician who was masked to group allocation analysed the data ; analyses included all participants who completed at least one follow-up question naire . After the 12 month follow-up , men in the st and ard care group were offered free self-testing kits for a year . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12613001236785 . FINDINGS Between Dec 1 , 2013 , and Feb 5 , 2015 , 182 men were r and omly assigned to self-testing , and 180 to st and ard care . The analysis population included 178 ( 98 % ) men in the self-testing group ( 174 person-years ) and 165 ( 92 % ) in the st and ard care group ( 162 person-years ) . Overall , men in the self-testing group had 701 HIV tests ( 410 self-tests ; mean 4·0 tests per year ) , and men in the st and ard care group had 313 HIV tests ( mean 1·9 tests per year ) ; rate ratio ( RR ) 2·08 ( 95 % CI 1·82 - 2·38 ; p<0·0001 ) . Among recent testers , men in the self-testing group had 627 tests ( 356 self-tests ; mean 4·2 per year ) , and men in the st and ard care group had 297 tests ( mean 2·1 per year ) ; RR 1·99 ( 1·73 - 2·29 ; p<0·0001 ) . Among non-recent testers , men in the self-testing group had 74 tests ( 54 self-tests ; mean 2·8 per year ) , and men in the st and ard care group had 16 tests ( mean 0·7 per year ) ; RR 3·95 ( 2·30 - 6·78 ; p<0·0001 ) . The mean number of facility-based HIV tests per year was similar in the self-testing and st and ard care groups ( mean 1·7 vs 1·9 per year , respectively ; RR 0·86 , 0·74 - 1·01 ; p=0·074 ) . No serious adverse events were reported during follow-up . INTERPRETATION HIV self-testing result ed in a two times increase in frequency of testing in gay and bisexual men at high risk of infection , and a nearly four times increase in non-recent testers , compared with st and ard care , without reducing the frequency of facility-based HIV testing . HIV self-testing should be made more widely available to help increase testing and earlier diagnosis . FUNDING The National Health and Medical Research Council , Australia Background : Changing community norms to increase awareness of HIV status and reduce HIV-related stigma has the potential to reduce the incidence of HIV-1 infection in the developing world . Methods : We developed and implemented a multilevel intervention providing community-based HIV mobile voluntary counseling and testing , community mobilization , and posttest support services . Forty-eight communities in Tanzania , Zimbabwe , South Africa , and Thail and were r and omized to receive the intervention or clinic-based st and ard voluntary counseling and testing ( VCT ) , the comparison condition . We monitored utilization of community-based HIV mobile voluntary counseling and testing and clinic-based st and ard VCT by community of residence at 3 sites , which was used to assess differential uptake . We also developed quality assurance procedures to evaluate staff fidelity to the intervention . Findings : In the first year of the study , a 4-fold increase in testing was observed in the intervention versus comparison communities . We also found an overall 95 % adherence to intervention components . Study outcomes , including prevalence of recent HIV infection and community-level HIV stigma , will be assessed after 3 years of intervention . Conclusions : The provision of mobile services , combined with appropriate support activities , may have significant effects on utilization of voluntary counseling and testing . These findings also provide early support for community mobilization as a strategy for increasing testing rates Background Following HIV-1 acquisition , many individuals develop an acute retroviral syndrome and a majority seek care . Available antibody testing can not detect an acute HIV infection , but repeat testing after 2–4 weeks may detect seroconversion . We assessed the effect of appointment reminders on attendance for repeat HIV testing . Methods We enrolled , in a r and omized controlled trial , 18–29 year old patients evaluated for acute HIV infection at five sites in Coastal Kenya ( Clinical Trials.gov NCT01876199 ) . Participants were allocated 1:1 to either st and ard appointment ( a date d appointment card ) or enhanced appointment ( a date d appointment card plus SMS and phone call reminders , or in-person reminders for participants without a phone ) . The primary outcome was visit attendance , i.e. , the proportion of participants attending the repeat test visit . Factors associated with attendance were examined by bivariable and multivariable logistic regression . Principal Findings Between April and July 2013 , 410 participants were r and omized . Attendance was 41 % ( 85/207 ) for the st and ard group and 59 % ( 117/199 ) for the enhanced group , for a relative risk of 1.4 [ 95 % Confidence Interval , CI , 1.2–1.7].Higher attendance was independently associated with older age , study site , and report of transactional sex in past month . Lower attendance was associated with reporting multiple partners in the past two months . Conclusions Appointment reminders through SMS , phone calls and in-person reminders increased the uptake of repeat HIV test by forty percent . This low-cost intervention could facilitate detection of acute HIV infections and uptake of recommended repeat testing . Trial Registration Clinical trials.gov Objective To determine if the provision of rapid HIV testing to men who have sex with men attending a health service would increase their frequency of HIV testing over time . Design Non-blinded r and omised controlled trial . Setting Public sexual health service in Australia . Participants Men who reported having a male sexual partner within the previous year and an HIV test within the previous two years . Of 400 men entered , 370 ( 92.5 % ) completed the study . Interventions Men attending the service between September 2010 and March 2011 were r and omised 1:1 to either ongoing access to rapid HIV testing obtained with finger prick or to conventional HIV serology with venepuncture , over 18 months . Main outcome measure The incidence of all HIV testing after enrolment , including testing outside the study clinic , analysed by intention to treat . Results Of 200 men r and omised to the rapid testing arm , 196 were followed for 288 person years . Of 200 men r and omised to the conventional testing arm , 194 were followed for 278 person years . Median time since the last HIV test was six months for both arms . Men in the rapid test arm had 469 tests ( mean 1.63 tests a year ) , and men in the conventional test arm had 396 tests ( mean 1.42 tests a year ) ; incidence rate ratio 1.15 , 95 % confidence interval 0.96 to 1.38 ; P=0.12 . In a post hoc analysis , rates of initial HIV testing during follow-up were 1.32 and 1.01 tests a year , respectively ( 1.32 , 1.05 to 1.65 ; P=0.02 ) . Conclusions Provision of access to rapid HIV testing in a health service did not result in a sustained increase over time in HIV testing by men who have sex with men ; however , the rate of initial HIV testing did increase by a third . Further research is required to determine how to achieve sustained increases in the frequency of HIV testing by population s at risk . Trial registration ACTR No 12610000430033 We conducted an in-person survey of New York City ( NYC ) pharmacies to assess the availability , accessibility , and price of the over-the-counter , rapid HIV self-test kit . NYC pharmacies were stratified into high , moderate and low morbidity neighborhoods by the HIV diagnosis rate of the neighborhood in which the pharmacy was located . A r and om sample of 500 pharmacies was taken [ 250 from high morbidity neighborhoods ( HighMN ) and 250 from low morbidity neighborhoods ( LowMN ) ] . Pharmacies were excluded if : closed during survey , non-retail , or > 10 min walk from subway . Project staff visited pharmacies to determine kit availability ( in pharmacy on day of survey ) , accessibility ( not locked/behind counter ) , and price ( marked on shelf/product ) . Of 361 pharmacies ( 161 LowMN ; 200 HighMN ) , kits were available in 27 % and accessible in 10 % ; there was no difference by neighborhood . Kits were most often kept behind the pharmacy counter ; this was more common in HighMN than in LowMN . Kits were kept solely behind the pharmacy counter in 52 % . Median price was US $ 42.99 without variability across neighborhoods . The rapid HIV self-test had limited availability and access in retail pharmacies . The high median price measured suggests that cost remained a barrier . ResumenLlevamos a cabo una encuesta a farmacias en la ciudad de Nueva York para evaluar la disponibilidad , acceso y precio del autoexamen rápido para el VIH ( prueba casera de VIH ) . Clasificamos los barrios de la ciudad de acuerdo a si tienen una taza de diagnósticos de VIH alta , moderada o baja , y tomamos una muestra aleatoria de 500 farmacias [ 250 en áreas con una taza de diagnósticos de VIH alta ( HighMN , por sus siglas en inglés ) y 250 en áreas con una taza de diagnósticos de VIH baja ( LowMN , por sus siglas en inglés ) ] . Se excluyeron las farmacias que : estaban cerradas durante el sondeo ; las que no atienden al público ; o las que se ubican más de 10 minutos camin and o de una parada del metro . El personal del estudio visitó las farmacias para determinar la disponibilidad ( de venta el día de la encuesta ) , el acceso ( en áreas libres o detrás del mostrador ) , y el precio de venta ( marcado en el estante o en el producto ) . De 361 farmacias visitadas ( 161 LowMN ; 200 HighMN ) , el autoexamen rápido para el VIH estaba disponible en el 27 % y accesible en áreas libres en el 10 % ; no hubo diferencias por tipo de barrio . En la mayoría ( 52 % ) de farmacias con pruebas disponibles , los autoexamenes se encontraban detrás del mostrador de la farmacia ; esto fue más común en HighMN que en LowMN . La mediana de precio fue de US $ 42.99 , sin diferencia por tipo de barrio . La disponibilidad y el libre acceso al autoexamen rápido para el VIH fueron limitados en farmacias . Su alto precio indica que el costo puede seguir siendo una barrera al acceso BACKGROUND In developing countries , most people infected with HIV do not know their infection status . We aim ed to assess whether HIV testing could be increased by combination of community mobilisation , mobile community-based voluntary counselling and testing ( VCT ) , and support after testing . METHODS Project Accept is underway in ten communities in Tanzania , eight in Zimbabwe , and 14 in Thail and . Communities at each site were paired according to similar demographic and environmental characteristics , and one community from each pair was r and omly assigned to receive st and ard clinic-based VCT ( SVCT ) , and the other community was assigned to receive community-based VCT ( CBVCT ) plus access to SVCT . R and omisation and assignment of communities to intervention groups was done by the statistics centre by computer ; no one was masked to treatment assignment because the interventions were community based . Intervention was provided for about 3 years ( 2006 - 09 ) . The primary endpoint of HIV incidence is pending completion of assessment s after the intervention . In this interim analysis , we examined the secondary endpoint of uptake in HIV testing , differences in characteristics of clients receiving their first HIV test , and repeat testing . Analyses were limited to clients aged 16 - 32 years . This study is registered with Clinical Trials.gov , number NCT00203749 . FINDINGS The proportion of clients receiving their first HIV test during the study was higher in CBVCT communities than in SVCT communities in Tanzania ( 2341 [ 37 % ] of 6250 vs 579 [ 9 % ] of 6733 ) , Zimbabwe ( 5437 [ 51 % ] of 10,700 vs 602 [ 5 % ] of 12,150 ) , and Thail and ( 7802 [ 69 % ] of 11,290 vs 2319 [ 23 % ] 10,033 ) . The mean difference in the proportion of clients receiving HIV testing between CBVCT and SVCT communities was 40·2 % ( 95 % CI 15·8 - 64·7 ; p=0·019 ) across three community pairs ( one per country ) . HIV prevalence was higher in SVCT communities than in CBVCT communities , but CBVCT detected almost four times more HIV cases than did SVCT across the three study sites ( 952 vs 264 ; p=0·003 ) . Repeat HIV testing in CBVCT communities increased in all sites to reach 28 % of all those testing for HIV by the end of the intervention period . INTERPRETATION CBVCT should be considered as a viable intervention to increase detection of HIV infection , especially in regions with restricted access to clinic-based VCT and support services after testing . FUNDING US National Institute of Mental Health , HIV Prevention Trials Network ( via US National Institute of Allergy and Infectious Diseases ) , and US National Institutes of Health In 2011 interim results of HIV Prevention Trials Network study 052 , a National Institutes of Health study design ed to test the effectiveness of antiretroviral treatment against the spread of HIV , were reported . These results showed that in a stable relationship in which one member of the couple was infected with HIV , treatment of the infected partner with antiretroviral drugs , combined with couples counseling and condom use , result ed in a 96 percent reduction in sexual transmission of HIV-1 . This finding led to the use of antiretroviral treatment as a cornerstone of HIV prevention . Independent advisory committees of the President 's Emergency Plan for AIDS Relief ( PEPFAR ) and the World Health Organization ( WHO ) have since issued analyses that set the stage for broader use of antiretroviral agents in treatment and prevention . This article describes the separate PEPFAR and WHO recommendations and outlines the design of prospect i ve new trials to test how best to maximize the benefits of early treatment for prevention Southeast Michigan accounts for over 70 % of all HIV/STI cases in the state , with young men who have sex with men ( YMSM ) between the ages of 13 and 24 encumbering the largest burden in HIV/STI incidence . Using community-based participatory research principles , we developed and pilot tested a web-based , r and omized control trial seeking to promote HIV/STI testing ( “ Get Connected ! ” ) among YMSM ( N = 130 ; ages 15–24 ) . R and omized participants completed a baseline assessment and shown a test-locator condition ( control ) or a tailored , personalized site ( treatment ) . At 30-day follow-up , we found high acceptability among YMSM in both conditions , yet higher credibility of intervention content among YMSM in the treatment group ( d = .55 ) . Furthermore , 30 participants reported testing by following , with the majority of these participants ( 73.3 % ; n = 22 ) completing the treatment condition , a clinical ly meaningful effect ( d = .34 ) suggesting preliminary efficacy for the intervention . These results demonstrate the potential of the intervention , and suggest that a larger efficacy trial may be warranted . ResumenEl Sudeste de Michigan contiene más del 70 % de todos los casos de VIH/ETS en el estado , con JHCH ( jóvenes hombres que tienen sexo con hombres ) entre las edades de 13 y 24 sufriendo la mayor incidencia de VIH/ETS . Utiliz and o los principios de investigación participativa y comunitaria , hemos desarrollado y examinado un proyecto piloto , con diseñode ensayo aleatorizado de control basado en promover la prueba de VIH/ETS ( “ Get Connected ! ” ) entre JHCH ( N = 130 entre los 15 y 24 años ) . Los JHCH completaron un cuestionario inicial y asignados a una condición control ( acceso a un localizador de pruebas ) o a un grupo de tratamiento ( un sitio web personalizado ) . A los 30 días de seguimiento , encontramos una alta aceptación a ambas condiciones de la intervención ; sin embargo , encontramos una mayor credibilidad al contenido entre los JHCH en el grupo de tratamiento ( d = .55 ) . Treinta participantes se reportaron haberse hecho una prueba de VIH/ETS durante el seguimiento , con la mayoría de los participantes ( 73.3 % , n = 22 ) siendo parte de la condición de tratamiento , un efecto clínicamente significativo ( d = .34 ) que sugiere la eficacia preliminar de la intervención . Estos result ados demuestran el potencial de laintervención , y sugieren un estudio de eficacia con una muestra más gr and e de JHCH OBJECTIVES Patients discharged from the emergency department ( ED ) are often referred for primary care , specialty , or other disease-specific follow-up appointments . Attendance at these scheduled follow-up appointments has been found to improve patient outcomes , decrease ED bounce-backs , and reduce mal practice risk . Reasons for missing follow-up visits are complex , but the most commonly reason cited by patients is simply forgetting . In this study the authors evaluated the ability of an automated text message reminder system to increase attendance at post-ED discharge follow-up appointments in a predominantly Hispanic safety-net population . METHODS This was a r and omized controlled trial of ED patients with outpatient follow-up visits scheduled at the time of ED discharge . A total of 374 English- and Spanish-speaking patients with text-capable mobile phones were enrolled . Patients in the intervention arm received automated , personalized text message appointment reminders including date , time , and clinic location at 7 , 3 , and 1 day before scheduled visits . A t-test of proportions was used to compare outcomes between intervention and control groups . Both an intention-to-treat ( ITT ) and a per- protocol analysis of the data were performed . The ITT more accurately reflects real-world conditions where errors such as number entry errors are bound to occur . The per- protocol analysis adds value by isolating the effect of the intervention by comparing patients who actually received it compared with those who did not . RESULTS In the per- protocol analysis of the primary outcome , the overall appointment adherence rate was 72.6 % in the intervention group compared with 62.1 % in the control group ( difference between groups = 10.5 % , 95 % confidence interval [ CI ] = 0.3 % to 20.8 % ; p = 0.045 ; number needed to treat = 9.5 ) . In the ITT analysis , the overall appointment attendance rate 70.2 % in the intervention group compared with 62.1 % in the control group ( difference between groups = 8.2 % ; 95 % CI = -1.6 % to 17.7 % ; p = 0.100 ) . In a secondary largely exploratory analysis , the intervention was found to have the most benefit in patients with the lowest baseline follow-up rate ( English speakers with specialty care appointments ) . CONCLUSIONS Automated text message appointment reminders result ed in improvement in attendance at scheduled post-ED discharge outpatient follow-up visits and represent a low-cost and highly scalable solution to increase attendance at post-ED follow-up appointments , which should be further explored in larger sample sizes and diverse patient population Improving HIV testing and counselling ( HTC ) requires a range of strategies . This article reports on HTC service delivery by Village Health Teams ( VHTs ) in Ug and a in the context of a model integrating this new component into pre-existing family planning services . Eight health centres from matched pairs were r and omly allocated to intervention or control . After being trained , 36 VHTs reporting to selected facilities in the intervention group started offering HTC along with family planning , while VHTs in the control group provided family planning only . Proficiency testing was conducted as external quality assurance . A survey of all 36 VHTs and 137 family planning clients in the intervention group and 119 clients in the control group and a review of record data were conducted after 10 months . Survey responses by VHTs and their clients in the intervention group demonstrate knowledge of counselling messages and safe testing . External quality assessment results provide additional evidence of competency . Eighty per cent of the family planning clients surveyed in the intervention group received an HIV test during the intervention ; 27 % of those were first-time testers . More clients had ever tested for HIV in the intervention group compared with the control ; clients also retested more often . Findings indicate that this model is feasible and acceptable for exp and ing quality HTC into communities . This study was registered with Clinical Trials.gov , number [ NCT02244398 ] |
10,328 | 30,753,490 | We detected unexplained inconsistency in evidence loops involving MIFE+MISO and adjusted for it .
EXP had lower effectiveness compared to other treatment options .
The effectiveness of medical treatments was similar compared to surgery .
WIDER IMPLICATION S Medical treatments for first-trimester miscarriage have similar effectiveness and side effects compared to surgery .
The addition of MIFE could increase the effectiveness of MISO and reduce side effects , although evidence is limited due to inconsistency .
EXP has lower effectiveness compared to other treatment options . | BACKGROUND First-trimester miscarriage affects up to a quarter of women worldwide .
With many competing treatment options available , there is a need for a comprehensive evidence synthesis .
OBJECTIVES AND RATIONALE We conducted a systematic review and network meta- analysis to assess the effectiveness and safety of treatment options for first-trimester miscarriage : expectant management ( EXP ) , sharp dilation and curettage ( D+C ) , electric vacuum aspiration ( EVAC ) , manual vacuum aspiration ( MVA ) , misoprostol alone ( MISO ) , mifepristone+misoprostol ( MIFE+MISO ) and misoprostol plus electric vacuum aspiration ( MISO+EVAC ) . | AIMS The purpose of this r and omized controlled clinical trial was to examine the effects of three couples-focused interventions and a control condition on women and men 's resolution of depression and grief during the first year after miscarriage . METHODS Three hundred forty-one couples were r and omly assigned to nurse caring ( NC ) ( three counseling sessions ) , self-caring ( SC ) ( three video and workbook modules ) , combined caring ( CC ) ( one counseling session plus three SC modules ) , or control ( no treatment ) . Interventions , based on Swanson 's Caring Theory and Meaning of Miscarriage Model , were offered 1 , 5 , and 11 weeks after enrollment . Outcomes included depression ( CES-D ) and grief , pure grief ( PG ) and grief-related emotions ( GRE ) . Differences in rates of recovery were estimated via multilevel modeling conducted in a Bayesian framework . RESULTS Bayesian odds ( BO ) ranging from 3.0 to 7.9 favored NC over all other conditions for accelerating women 's resolution of depression . BO of 3.2 - 6.6 favored NC and no treatment over SC and CC for resolving men 's depression . BO of 3.1 - 7.0 favored all three interventions over no treatment for accelerating women 's PG resolution , and BO of 18.7 - 22.6 favored NC and CC over SC or no treatment for resolving men 's PG . BO ranging from 2.4 to 6.1 favored NC and SC over CC or no treatment for hastening women 's resolution of GRE . BO from 3.5 to 17.9 favored NC , CC , and control over SC for resolving men 's GRE . CONCLUSIONS NC had the overall broadest positive impact on couples ' resolution of grief and depression . In addition , grief resolution ( PG and GRE ) was accelerated by SC for women and CC for men OBJECTIVE To compare the efficacy of intramuscular methotrexate plus vaginal misoprostol to vaginal misoprostol alone in completing abortion in women with non-viable early first trimester pregnancy . METHOD Twenty-one women with non-viable pregnancy up to 49 days gestation were r and omized to receive intramuscular methotrexate , followed 2 days later by vaginal misoprostol or misoprostol alone . We also collected patient satisfaction information . RESULT Complete abortion occurred in all 12 ( 100 % ) women in the combined group and eight of nine ( 89 % , RR = 1.13 , CI 0.89 - 1.42 ) women in the misoprostol only group . Of the women , 75 % rated their experience as good and would choose medical management again . CONCLUSION Either methotrexate plus misoprostol or misoprostol alone effectively completed abortion in women with non-viable early pregnancy and represent acceptable medical alternatives to surgery or expectant management 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 This study was design ed to investigate the use of oral mifepristone ( RU 486 ) for the induction of natural expulsion of concepti in women with spontaneously interrupted pregnancy in the first trimester . It consisted of a double-blind placebo-controlled study of mifepristone ( 600 mg ) against placebo . A total of 46 women consulting for interrupted pregnancy were diagnosed at ultrasound with no clinical sign of miscarriage . Measurements were made of the occurrence of natural expulsion , the frequency of complete expulsion , the need for subsequent surgical evacuation , analgesia and the need for transfusion . Natural expulsion occurred within 5 days in 82 % of patients receiving mifepristone treatment versus 8 % of placebo-treated patients ( P < 0.001 ) . All patients experienced bleeding after RU 486 and two needed emergency aspiration for haemorrhagic expulsion . The treatment failed in four patients , who underwent evacuation under local anaesthesia . In the control group , 19 patients underwent evacuation under local ( n = 10 ) or general ( n = 9 ) anaesthesia . It was concluded that a st and ard oral pilot dose of 600 mg of mifepristone induces natural expulsion in 82 % of women with non-developing first trimester intrauterine pregnancies BACKGROUND Misoprostol is effective for cervical priming prior to suction evacuation in first trimester pregnancy termination . This is the first r and omized study to compare vaginal misoprostol versus expectant treatment in women presenting with spontaneous miscarriage . METHODS Sixty women presenting with spontaneous miscarriage were recruited to the study at the Queen Mary Hospital between 1998 and 1999 . They were r and omized to group 1 : misoprostol ; and group 2 : expectant management . Women in the misoprostol group received vaginal misoprostol 400 microg on days 1 , 3 and 5 . The expectant group was followed up according to the same schedule . Suction evacuation was performed if there was excessive bleeding or abdominal pain ; or if a gestational sac was detected by transvaginal scan on day 15 . RESULTS Fifty-nine women completed the trial . Those who did not require suction evacuation up to the time of return of normal menstruation were considered to be successful . The incidence of side-effects was comparable between the two groups . Three women in the expectant group and one in the misoprostol group underwent emergency suction evacuation because of excessive bleeding . The mean duration of vaginal bleeding was similar for both groups ( 14.6 days in the misoprostol group versus 15.0 days in the expectant group ) . The successful rate in the misoprostol group was significantly higher than that of the expectant group ( 83.3 versus 48.3 % , P < 0.05 ) . CONCLUSION We recommend repeated vaginal misoprostol 400 microg given on days 1 , 3 and 5 as a treatment option for women with first trimester spontaneous miscarriage OBJECTIVE To examine rates of conception and pregnancy loss and their relations with time to clinical pregnancy and reproductive outcomes . DESIGN A prospect i ve observational study . SETTING Population -based cohort in China . PATIENT(S ) Five hundred eighteen healthy newly married women who intended to conceive . Upon stopping contraception , daily records of vaginal bleeding and daily first-morning urine specimens were obtained for < or = 1 year or until a clinical pregnancy was achieved . Daily urinary hCG was assayed to detect early pregnancy loss ( EPL ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Conception , pregnancy loss , and time to clinical pregnancy . RESULT ( S ) The conception rate per cycle was 40 % over the first 12 months . Of the 618 detectable conceptions , 49 ( 7.9 % ) ended in clinical spontaneous abortion , and 152 ( 24.6 % ) in EPL . Early pregnancy loss was detected in 14 % of all the cycles without clinical ly recognized pregnancy , but the frequencies were lower among women with delayed time to clinical pregnancy . Early pregnancy loss in the preceding cycle was associated with increased odds of conception ( odds ratio [ OR ] , 2.6 ; 95 % confidence interval [ CI ] , 1.8 - 3.9 ) , clinical pregnancy ( OR , 2.0 ; 95 % CI , 1.3 - 3.0 ) , and EPL ( OR , 2.4 ; 95 % CI , 1.4 - 4.2 ) but was not associated with spontaneous abortion , low birth weight , or preterm birth in the subsequent cycle . CONCLUSION ( S ) We demonstrated substantial EPL in the non- clinical ly pregnant cycles and a positive relation between EPL and subsequent fertility Abstract Objective To ascertain whether a clinical ly important difference exists in the incidence of gynaecological infection between surgical management and expectant or medical management of miscarriage . Design R and omised controlled trial comparing medical and expectant management with surgical management of first trimester miscarriage . Setting Early pregnancy assessment units of seven hospitals in the United Kingdom . Participants Women of less than 13 weeks ' gestation , with a diagnosis of early fetal demise or incomplete miscarriage . Interventions Expectant management ( no specific intervention ) ; medical management ( vaginal dose of misoprostol preceded , for women with early fetal demise , by oral mifepristone 24 - 48 hours earlier ) ; surgical management ( surgical evacuation ) . Main outcome measures Confirmed gynaecological infection at 14 days and eight weeks ; need for unplanned admission or surgical intervention . Results 1200 women were recruited : 399 to expectant management , 398 to medical management , and 403 to surgical management . No differences were found in the incidence of confirmed infection within 14 days between the expectant group ( 3 % ) and the surgical group ( 3 % ) ( risk difference 0.2 % , 95 % confidence interval − 2.2 % to 2.7 % ) or between the medical group ( 2 % ) and the surgical group ( 0.7 % , − 1.6 % to 3.1 % ) . Compared with the surgical group , the number of unplanned hospital admissions was significantly higher in both the expectant group ( risk difference − 41 % , − 47 % to − 36 % ) and the medical group ( − 10 % , − 15 % to − 6 % ) . Similarly , when compared with the surgical group , the number of women who had an unplanned surgical curettage was significantly higher in the expectant group ( risk difference − 39 % , − 44 % to − 34 % ) and the medical group ( − 30 % , − 35 % to − 25 % ) . Conclusions The incidence of gynaecological infection after surgical , expectant , and medical management of first trimester miscarriage is low ( 2 - 3 % ) , and no evidence exists of a difference by the method of management . However , significantly more unplanned admissions and unplanned surgical curettage occurred after expectant management and medical management than after surgical management . Trial registration National Research Register : N0467011677/N0467073587 Abstract Objective To compare the efficacy and safety of mifepristone followed by misoprostol with misoprostol alone in the management of early pregnancy failure ( EPF ) . Study Design A r and omized double-blind placebo-controlled clinical trial . Methods Ninety-two women with EPF ≤12 weeks were recruited and r and omly allocated to receive either mifepristone 200 mg ( n = 46 ) or placebo ( n = 46 ) . Forty-eight hours later , patients in both the groups were given 800 µg misoprostol per-vaginum . If no expulsion occurred within 4 h , repeat doses of 400 µg misoprostol were given orally at 3-hourly interval to a maximum of 2 doses in women ≤9 weeks by scan and 4 doses in women > 9 weeks by scan . Results Pre-treatment of misoprostol with mifepristone significantly increased the complete abortion rate ( 86.7 vs. 57.8 % , p = 0.009 ) and , hence , reduced the need for surgical evacuation ( 13.3 vs. 42.2 % , p = 0.002 ) , induction to expulsion interval ( 4.74 ± 2.24 vs. 8.03 ± 2.77 h , p = 0.000 ) , mean number of additional doses of misoprostol required ( 0.68 vs. 1.91 , p = 0.000 ) , and side effects . Conclusion Use of mifepristone prior to misoprostol in EPF significantly improves the efficacy and reduces the side effects of misoprostol alone OBJECTIVE To compare the effect of vaginal misoprostol with that of placebo when used prior to dilation and aspiration in women with a missed abortion . METHOD Eighty-four pregnant women with a missed abortion were r and omized to receive either vaginal misoprostol ( 200 micrograms ) or placebo the day before the planned dilatation and aspiration under inhalation anesthesia . RESULT Thirty-five women ( 83.33 % ) in the misoprostol group and 6 women ( 17.14 % ) in the placebo group aborted spontaneously prior to the scheduled dilatation and aspiration , P < 0.0001 . The mean insertion to spontaneous expulsion time was 11.63 + /- 6.14 h in the misoprostol group compared to 11.95 + /- 5.43 h in placebo . In the misoprostol group two women required intramuscular pethidine for analgesia . In the placebo group there were two cases of blood loss in excess of 500 ml and one woman with a uterine perforation . CONCLUSION Vaginal administration of misoprostol to women with a missed abortion produced spontaneous expulsion of the pregnancy and reduced the need for surgical treatment BACKGROUND Mifepristone and a prostagl and in have been used successfully to terminate pregnancy in Europe and China . We report the results of a large U.S. study of mifepristone and misoprostol in women with pregnancies of up to nine weeks ' duration . METHODS We administered 600 mg of mifepristone and then 400 microg of misoprostol two days later to 2121 women seeking termination of their pregnancies at 17 centers . The women were observed for four hours after the administration of misoprostol and returned on day 15 for final assessment . RESULTS Two thous and fifteen women completed the final assessment . Among them , pregnancy was terminated in 762 of the 827 women pregnant for < or = 49 days ( 92 percent ) , 563 of the 678 women pregnant for 50 to 56 days ( 83 percent ) , and 395 of the 510 women pregnant for 57 to 63 days ( 77 percent ) ( P<0.001 ) . Termination occurred within 4 hours after the administration of misoprostol in 49 percent of the women and within 24 hours in 75 percent . Failures , defined as cases requiring surgical intervention for medical reasons or because the patient requested it , the abortion was incomplete , or the pregnancy was ongoing , increased with increasing duration of pregnancy . The largest increase was in failures representing ongoing pregnancy , which increased from 1 percent in the < or = 49-days group to 9 percent in the 57-to-63-days group ( P<0.001 ) . Abdominal pain , nausea , vomiting , diarrhea , and vaginal bleeding also increased with advancing gestational age . Two percent of the women in the < or = 49-days group , as compared with 4 percent in each of the other two groups , were hospitalized , underwent surgical interventions , and received intravenous fluids ( P=0.008 ) . CONCLUSIONS This mifepristone-misoprostol regimen is effective in terminating pregnancies , especially in women with pregnancies of 49 days ' duration or less Cost effectiveness of managing 107 incomplete abortions by manual vacuum aspiration ( MVA ) is compared with management of 92 incomplete abortions by evacuation by curettage ( E by C ) at Muhimbili Medical Centre ( September-November 1992 ) . Pre-evacuation waiting times , duration of procedures and duration of hospital stay were less for MVA as compared to E by C. The total pre-evacuation waiting time , the duration s of the procedure and hospital stay were 15.59 days ( 55.11 % ) , 10.96 ( 46.41 % ) hours and 21.23 ( 40.53 % ) days less for MVA as compared to E by C. The direct costs revealed a cost differential of MVA over E by C of Tshs 776.9 ( US$ 2.6 ) . MVA is more cost effective than contemporary E by C and its introduction on a wider scale in our health care delivery system is recommended Miscarriage treated surgically and medically were compared in a r and omised controlled trial evaluating pain and bleeding . Surgery is associated with less pain ( P < 0.03 ) and vaginal bleeding ( duration and severity , P = 0.001 ) than medical treatment , fewer daily hospital attendances ( 2.5 compared with three , P = 0.04 ) but a greater drop in haemoglobin concentration ( difference , 1 g/dl ; CI95 % = 0.3 - 1.6 ) OBJECTIVE To determine whether misoprostol medical management of early pregnancy failures is more effective than expectant management . STUDY DESIGN Patients diagnosed with early pregnancy failures , closed cervix , and minimal vaginal bleeding were r and omized to 800 microg of misoprostol or placebo placed vaginally . Patients were evaluated by ultrasound imaging 24 hours and 48 hours after study drug administration , with repeat administration if 24-hour imaging showed a persistent gestational sac . Treatment success was defined as expulsion of uterine contents within 48 hours . Patient follow-up occurred 2 weeks after expulsion of uterine contents . RESULTS Treatment success occurred in 15 of 18 ( 83 % ) misoprostol patients and 2 of 16 ( 13 % ) placebo patients ( P < .0001 ) . Side effects were similar between groups except for vaginal bleeding , which was more common in the misoprostol group ( P = .001 ) . Patient satisfaction and pain perception were similar between groups . CONCLUSION Misoprostol appears to be highly effective for treating early pregnancy failures , with few side effects and high patient satisfaction Objective To compare the efficacy of antiprogesterone ( mifepristone ) in combination with a synthetic prostagl and in E , analogue ( misoprostol ) for outpatient treatment of miscarriages Objectives To study if misoprostol 400 μg , administered vaginally , increased the successful resolution of early miscarriage compared with placebo Searle , Chicago , IL , USA ) with that of dinoprostone ( Prostin E2 , Pharmacia & Upjohn N.V.y S.A. , Puurs , Belgium ) in the treatment of missed abortion , 60 women with a diagnosis of missed abortion were r and omly allocated to treatment with either vaginal misoprostol or dinoprostone in a prospect i ve r and omized study at Tawam Hospital — a teaching hospital tertiary care unit in the United Arab Emirates . Diagnosis of missed abortion was based on ultrasonographic demonstration of an embryo greater than 7 mm with no cardiac activity or of irregular gestational sac with mean sac diameter greater than 16 mm w1x . A group BACKGROUND We aim ed to determine whether outpatient treatment of miscarriage with vaginal misoprostol is more effective than expectant management in reducing the need for surgical evacuation of retained products of conception ( ERPC ) . METHODS Of 131 eligible women with first trimester miscarriage , 104 agreed to r and omization to either 600 microg misoprostol or placebo intravaginally . They were assessed the following day and administered a second dose of their allocated treatment if miscarriage was not complete . Those not successful after two doses were seen on day 7 , and , if miscarriage was not complete , an ERPC was performed . RESULTS The success rate of medical management was 88.5 % ( 46/52 ) compared with 44.2 % ( 23/52 ) for expectant management . There was no significant difference in success rate ( 100 versus 85.7 % ) in women treated with an incomplete miscarriage . Women with early pregnancy failure had a success rate of 87 % with misoprostol compared with 29 % with expectant management [ odds ratio ( OR ) 15.96 ; 95 % confidence interval ( CI ) 5.26 , 48.37 ] . The complete miscarriage rate was achieved quicker in the medical group than the expectant group by day 1 ( 32.7 versus 5.8 % ) and by day 2 ( 73.1 versus 13.5 % ) of treatment . There were no differences in side-effects , bleeding duration , analgesia use , pain score and satisfaction with treatment . Women in the expectant group made more outpatient visits ( 5.06 versus 4.44 % ; OR = -0.62 , 95 % CI -1.04 , -0.19 ) . More women in the medical group ( 90.4 versus 73.1 % ; OR 1.26 , 95 % CI 1.05 , 1.50 ) would elect the same treatment in the future . CONCLUSIONS Medical management using 600 microg misoprostol vaginally is more effective than expectant management of early pregnancy failure . Misoprostol did not increase the side-effect profile and patient acceptability was superior to expectant management Objective To assess the effectiveness and acceptability of oral misoprostol , self‐administered 12 h before surgery , as a cervical priming agent prior to day case suction termination of pregnancy |
10,329 | 31,147,780 | By cognitive domain , objective improvements in memory were most commonly reported , followed by executive functions and processing speed . | Purpose Individuals with non- central nervous system ( CNS ) cancers can experience cancer-related cognitive dysfunction ( CRCD ) , negatively impacting daily functioning and quality of life .
This systematic review examined cognitive rehabilitation programs aim ed at improving cognitive function . | PURPOSE Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration . Whether chemotherapy has any long-term effects on cognition is largely unknown , yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival . We investigated whether cyclophosphamide , methotrexate , and fluorouracil ( CMF ) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment . PATIENTS AND METHODS This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment ( six cycles ; average time since treatment , 21 years ; n = 196 ) to that of a population -based sample of women never diagnosed with cancer ( n = 1,509 ) . Participants were between 50 and 80 years of age . Exclusion criteria were ever use of adjuvant endocrine therapy , secondary malignancy , recurrence , and /or metastasis . RESULTS The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate ( P = .015 ) and delayed verbal memory ( P = .002 ) , processing speed ( P < .001 ) , executive functioning ( P = .013 ) , and psychomotor speed ( P = .001 ) . They experienced fewer symptoms of depression ( P < .001 ) , yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance . CONCLUSION Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse , on average , than r and om population controls on neuropsychological tests . The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy . This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting Although the impact of cancer and associated treatments on cognitive functioning is becoming an increasingly recognized problem , there are few published studies that have investigated psychological interventions to address this issue . A waitlist r and omized controlled trial methodology was used to assess the efficacy of a group cognitive rehabilitation intervention ( “ ReCog ” ) that successfully targeted cancer-related cognitive decline in previously published pilot research . Participants were 29 cancer survivors who were r and omly allocated to either the intervention group or a waitlist group who received the intervention at a later date , and 16 demographically matched community volunteers with no history of cancer ( trial registration ACTRN12615000009516 , available at http://www.ANZCTR.org.au/ACTRN12615000009516.aspx ) . The study was the first to include an adapted version of the Traumatic Brain Injury Self-Efficacy Scale to assess cognitive self-efficacy ( CSE ) in people who have experienced cancer . Results revealed participating in the intervention was associated with significantly faster performance on one objective cognitive task that measures processing speed and visual scanning . Significantly larger improvements for the intervention group were also found on measures of perceived cognitive impairments and CSE . There was some evidence to support the roles of CSE and illness perceptions as potential mechanisms of change for the intervention . Overall , the study provided additional evidence of feasibility and efficacy of group psychological intervention for targeting cancer-related cognitive decline OBJECTIVE This research aim ed to address the gap in evidence -based treatment available for cancer survivors who are experiencing cognitive dysfunction , through piloting a novel treatment intervention . The overall research question was whether a group cognitive rehabilitation intervention would be feasible for improving cognitive function and quality of life for people who have completed cancer treatment . METHODS Three groups of adults were recruited as follows : an intervention group of 23 cancer survivors who completed a 4-week group cognitive rehabilitation treatment , a comparison group of nine cancer survivors , and a community sample of 23 adults who had never experienced cancer . Measures of objective and subjective cognitive function , quality of life , psychosocial distress , and illness perceptions were used . The research design was non-r and omised . RESULTS The results indicated that the intervention was effective in improving overall cognitive function , visuospatial/constructional performance , immediate memory , and delayed memory beyond practice effects alone . It was helpful in reducing participants ' perceptions of cognitive impairment and psychosocial distress , as well as promoting social functioning and underst and ing of cognition . The improvements were maintained at 3 months after the intervention . Participants reported a high level of satisfaction with the treatment . CONCLUSIONS The results provided evidence for the feasibility of a brief group-based cognitive rehabilitation intervention to treat cognitive problems experienced by cancer survivors Purpose / Objectives : To test combining a group intervention to build self‐efficacy for using compensatory strategies and lifestyle adjustments with brain‐training practice to improve cognition . Design : A quasiexperimental design . Setting : Texas Oncology , a community oncology practice in Austin . Sample : 20 women aged 35‐65 years , who had finished chemotherapy at least three months before the study , were within five years of completing all treatment , and had self‐reported cognitive concerns . Methods : Six group sessions to build self‐efficacy for using compensatory strategies , along with other health behaviors that affect cognitive performance , were combined with practice on a computer‐based training program . Female breast cancer survivors were recruited through flyers , mailings , and personal contacts . Main Research Variables : Cognitive performance , cognitive concerns , cognitive/memory strategies , fatigue , emotional distress , sleep disorders , and quality of life . Findings : Participants reported that the intervention was useful in building cognitive abilities . Although scores on performance tests did not increase , ratings of cognitive concerns , fatigue , emotional distress , and sleep disturbance decreased significantly . Use of cognitive/memory strategies increased significantly . Conclusions : This pilot study demonstrated the feasibility of combining a group intervention with brain‐training practice . A larger r and omized trial would afford a more rigorous test of efficacy . Implication s for Nursing : A growing body of evidence regarding potential interventions to address survivors ’ cognitive problems exists . Nurses should counsel breast cancer survivors about fatigue , sleep deprivation , and emotional distress , as well as the effects of cancer treatment on cognition Background Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy ; this explanation , however , fails to account for cognitive dysfunction observed in chemotherapy-naïve patients . In a controlled , longitudinal , multisite study , we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress . Methods Newly diagnosed breast cancer patients and healthy control subjects , age 65 or younger , underwent three assessment s within one year , including paper- and -pencil and computerized neuropsychological tests , clinical diagnostics of post-traumatic stress disorder ( PTSD ) , and self-reported cognitive function . Analysis of variance was used to compare three groups of participants - patients who did or did not receive chemotherapy and healthy control subjects-on age- and education-corrected cognitive performance and cognitive change . Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models . All statistical tests were two-sided . Results Of 226 participants ( 166 patients and 60 control subjects ) , 206 completed all assessment sessions ( attrition : 8.8 % ) . Patients demonstrated overall cognitive decline ( group*time effect on composite z -score : -0.13 , P = .04 ) and scored consistently worse on Go/Nogo errors . The latter effect was mediated by PTSD symptoms ( mediation effect : B = 0.15 , 95 % confidence interval = 0.02 to 0.38 ) . Only chemotherapy patients showed declined reaction time on a computerized alertness test . Overall cognitive performance correlated with self-reported cognitive problems at one year ( T = -0.11 , P = .02 ) . Conclusions Largely irrespective of chemotherapy , breast cancer patients may encounter very subtle cognitive dysfunction , part of which is mediated by cancer-related post-traumatic stress . Further factors other than treatment side effects remain to be investigated Importance Neurocognitive deficits ( NCD ) have been observed in non central nervous system cancers , yet short- and long-term neurocognitive data on patients treated for head and neck cancer ( HNC ) are lacking . Objective To assess objective neurocognitive function before and after definitive radiation therapy for HNC . Design , Setting , and Participants In a prospect i ve , longitudinal study , neurocognitive function and self-reported symptoms were assessed in 80 patients with histologically proven HNC requiring definitive chemoradiotherapy or radiotherapy and in 40 healthy controls 4 times ( baseline , 6 , 12 , and 24 months after baseline ) prior to commencing treatment at Princess Margaret Cancer Centre , Toronto , Canada . Main Outcomes and Measures Neurocognitive test scores were converted to age-corrected z scores ( mean , 0 ; st and ard deviation , 1 ) and reported as mean scores , st and ardized regression-based scores , and frequencies of impairments in intellectual capacity , concentration , memory , executive function , processing speed , and motor dexterity . Multivariable analysis was used to identify factors associated with NCD 2 years after treatment . Results Eighty patients and 40 healthy controls enrolled . Analyses revealed significant differences between patient and control mean performance in some domains , with patient deficits increasing over time : intellectual capacity ( Cohen d , effect sizes [ 95 % CIs ] of −0.46 [ −0.64 to 0.30 ] , −0.51 [ −0.72 to −0.30 ] , and −0.70 [ −0.92 to −0.49 ] for time points 6 , 12 , and 24 months , respectively ) ; concentration/short-term attention span ( −0.19 [ −0.37 to 0.00 ] , −0.38 [ −0.55 to −0.21 ] , −0.54 [ −0.71 to −0.37 ] ) ; verbal memory ( −0.16 [ −0.33 to 0.02 ] , −0.38 [ −0.64 to −0.12 ] , −0.53 [ −0.74 to −0.32 ] ) ; executive function ( −0.14 [ −0.27 to 0.00 ] , −0.34 [ −0.52 to −0.16 ] , −0.43 [ −0.64 to −0.22 ] ) , and global cognitive function composite ( −0.38 [ −0.55 to −0.22 ] , −0.75 [ −0.92 to −0.58 ] , −1.06 [ −1.26 to −0.86 ] ) . There was an increased rate of impaired global neurocognitive functioning among patients ( 38 % ) at 24 months compared with controls ( 0 % ) . Neurocognitive deficits were not associated with baseline cytokines . Conclusions and Relevance Head and neck cancer survivors have neurocognitive sequelae up to 2 years after definitive chemoradiotherapy or radiation treatment . Patients and health care teams should know about such potential risks . Further research is warranted in search of strategies to avoid , reduce , and compensate for declines OBJECTIVE Although chemotherapy-induced cognitive impairment is common among breast cancer patients , evidence for effective interventions addressing cognitive deficits is limited . This r and omized controlled trial examined the feasibility and preliminary efficacy of a Tibetan Sound Meditation ( TSM ) program to improve cognitive function and quality of life in breast cancer patients . METHODS Forty-seven breast cancer patients ( mean age 56.3 years ) , who were staged I-III at diagnosis , 6 - 60 months post-chemotherapy , and reported cognitive impairment at study entry were recruited . Participants were r and omized to either two weekly TSM sessions for 6 weeks or a wait list control group . Neuropsychological assessment s were completed at baseline and 1 month post-treatment . Self-report measures of cognitive function ( Functional Assessment of Cancer Therapy (FACT)-Cog ) , quality of life ( SF-36 ) , depressive symptoms ( Center for Epidemiologic Studies Depression Scale ) , sleep disturbance ( Pittsburgh Sleep Quality Index ) , fatigue ( Brief Fatigue Inventory ) , and spirituality ( FACT-Sp ) were completed at baseline , the end of treatment , and 1 month later . RESULTS Relative to the control group , women in the TSM group performed better on the verbal memory test ( Rey Auditory Verbal Learning Test trial 1 ) ( p = 0.06 ) and the short-term memory and processing speed task ( Digit Symbol ) ( p = 0.09 ) and reported improved cognitive function ( p = 0.06 ) , cognitive abilities ( p = 0.08 ) , mental health ( p = 0.04 ) , and spirituality ( p = 0.05 ) at the end of treatment but not 1 month later . CONCLUSIONS This r and omized controlled trial revealed that TSM program appears to be a feasible and acceptable intervention and may be associated with short-term improvements in objective and subjective cognitive function as well as mental health and spirituality in breast cancer patients The purpose of this study was to evaluate the preliminary efficacy and satisfaction/acceptability of training in memory or speed of processing versus wait-list control for improving cognitive function in breast cancer survivors . 82 breast cancer survivors completed a three-group r and omized , controlled trial . Primary outcomes were objective neuropsychological tests of memory and speed of processing . Secondary outcomes were perceived cognitive functioning , symptom distress ( mood disturbance , anxiety , and fatigue ) , quality of life , and intervention satisfaction/acceptability . Data were collected at baseline , post-intervention , and 2-month follow-up . Using repeated- measures mixed-linear ANCOVA models , each intervention was compared to wait-list control while adjusting for age , education , and baseline measures . The effect sizes for differences in means and the reliable improvement percentage were reported . The results show that domain-specific effects were seen for both interventions : memory training improved memory performance at 2-month follow-up ( p = 0.036 , d = 0.59 ) ; speed of processing training improved processing speed post-intervention ( p = 0.040 , d = 0.55 ) and 2-month follow-up ( p = 0.016 ; d = 0.67 ) . Transfer effects to non-trained domains were seen for speed of processing training with improved memory post-intervention ( p = 0.007 , d = 0.75 ) and 2-month follow-up ( p = 0.004 , d = 0.82 ) . Both interventions were associated with improvements in perceived cognitive functioning , symptom distress , and quality of life . Ratings of satisfaction/acceptability were high for both interventions . It was concluded that while both interventions appeared promising , speed of processing training result ed in immediate and durable improvements in objective measures of processing speed and verbal memory . Speed of processing training may have broader benefits in this clinical population PURPOSE To examine the impact of age and cognitive reserve on cognitive functioning in patients with breast cancer who are receiving adjuvant treatments . PATIENTS AND METHODS Patients with breast cancer exposed to chemotherapy ( n = 60 ; mean age , 51.7 years ) were evaluated with a battery of neuropsychological and psychological tests before treatment and at 1 , 6 , and 18 months after treatment . Patients not exposed to chemotherapy ( n = 72 ; mean age , 56.6 years ) and healthy controls ( n = 45 ; mean age , 52.9 years ) were assessed at matched intervals . RESULTS Mixed-effects modeling revealed significant effects for the Processing Speed and Verbal Ability domains . For Processing Speed , a three-way interaction among treatment group , age , and baseline cognitive reserve ( P < .001 ) revealed that older patients with lower baseline cognitive reserve who were exposed to chemotherapy had lower performance on Processing Speed compared with patients not exposed to chemotherapy ( P = .003 ) and controls ( P < .001 ) . A significant group by time interaction for Verbal Ability ( P = .01 ) suggested that the healthy controls and no chemotherapy groups improved over time . The chemotherapy group failed to improve at 1 month after treatment but improved during the last two follow-up assessment s. Exploratory analyses suggested a negative effect of tamoxifen on Processing Speed ( P = .036 ) and Verbal Memory ( P = .05 ) in the no-chemotherapy group . CONCLUSION These data demonstrated that age and pretreatment cognitive reserve were related to post-treatment decline in Processing Speed in women exposed to chemotherapy and that chemotherapy had a short-term impact on Verbal Ability . Exploratory analysis of the impact of tamoxifen suggests that this pattern of results may be due to a combination of chemotherapy and tamoxifen 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 PURPOSE To evaluate the influence of adjuvant tamoxifen and exemestane on cognitive functioning in postmenopausal patients with breast cancer ( BC ) . PATIENTS AND METHODS Neuropsychological assessment s were performed before the start ( T1 ) and after 1 year of adjuvant endocrine treatment ( T2 ) in Dutch postmenopausal patients with BC , who did not receive chemotherapy . Patients participated in the international Tamoxifen and Exemestane Adjuvant Multinational trial , a prospect i ve r and omized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive BC . RESULTS Participants included 80 tamoxifen users ( mean age , 68.7 years ; range 51 to 84 ) , 99 exemestane users ( mean age , 68.3 years ; range , 50 to 82 ) , and 120 healthy controls ( mean age , 66.2 years ; range , 49 to 86 ) . At T2 , after adjustment for T1 performance , exemestane users did not perform statistically significantly worse than healthy controls on any cognitive domain . In contrast , tamoxifen users performed statistically significantly worse than healthy controls on verbal memory ( P < .01 ; Cohen 's d = .43 ) and executive functioning ( P = .01 ; Cohen 's d = .40 ) , and statistically significantly worse than exemestane users on information processing speed ( P = .02 ; Cohen 's d = .36 ) . With respect to visual memory , working memory , verbal fluency , reaction speed , and motor speed , no significant differences between the three groups were found . CONCLUSION After 1 year of adjuvant therapy , tamoxifen use is associated with statistically significant lower functioning in verbal memory and executive functioning , whereas exemestane use is not associated with statistically significant lower cognitive functioning in postmenopausal patients with BC . Our results accentuate the need to include assessment s of cognitive effects of adjuvant endocrine treatment in long-term safety studies To assess the feasibility of a cognitive rehabilitation program in breast cancer survivors ( BCS ) with persistent post-treatment cognitive complaints . BCS with cognitive complaints , 18-months to 5-years post-treatment , were recruited for a once-weekly , five-week , group cognitive training intervention . Outcome measures included self-reported mood and cognitive function , and neurocognitive tests administered at pre-intervention , immediate- , two-month and four-month post-intervention . A sub- study in eight participants evaluated resting state quantitative electroencephalography ( qEEG ) changes from pre- to immediate post-intervention in relationship to post-intervention changes in cognitive complaints . Twenty-seven BCS completed the protocol and tolerated the intervention well . We observed significant reductions in total and memory-specific cognitive complaints from pre-intervention to immediate post-intervention ( p = 0.031 and p = 0.009 , respectively ) and at four-months post-intervention ( p < 0.0001 and p < 0.001 , respectively ) . Significant improvement in neurocognitive tests were found for Symbol Digit , Stroop , and Trails A tests ( df = 26 , all p ’s < 0.05 ) . Effect sizes for changes from pre-intervention to immediate and to four-month post intervention ranged from 0.429 to 0.607 , and from 0.439 to 0.741 , respectively . Increase in qEEG absolute alpha power over the course of the intervention was associated with reduced complaints at immediate post-intervention ( r = −0.78 , p = 0.021 ) , two-months ( r range = −0.76 to −0.82 , p-value range 0.004 to 0.03 ) , and four-months ( r = −0.71 , p = 0.048 ) . A five-week group cognitive training intervention is feasible and well tolerated . Cognitive complaints and neurocognitive test performances showed positive changes . qEEG may serve as a potential biomarker for improvement in self-reported complaints . A r and omized clinical trial is underway to test the efficacy of the intervention Purpose Prostate cancer patients who have undergone and rogen deprivation therapy ( ADT ) may experience cognitive impairment , yet there is an unmet need for nonpharmacological interventions to address cognitive impairment in this population . This study examines the feasibility , acceptability , and preliminary efficacy of a home-based computerized cognitive training ( CCT ) program to treat cancer-related cognitive impairment . Methods Sixty men who had received ≥ 3 months of ADT were screened for at least mild cognitive or neurobehavioral impairment and r and omized to 8 weeks of CCT or usual care . Follow-up assessment s occurred immediately post-intervention or equivalent ( T2 ) and 8 weeks later ( T3 ) . The acceptability of CCT was also assessed . Results Feasibility : A priori feasibility thresholds were partially met ( i.e. , r and omization rate > 50 % , retention rate > 70 % excluding CCT drop-outs , but < 70 % for intent-to-treat ) . Acceptability : Participants were mostly satisfied with CCT and found it somewhat enjoyable , though barriers to uptake existed . Preliminary efficacy : Linear mixed models indicated significant time by group effects favorable to CCT in reaction time ( p = .01 ) , but unfavorable to CCT in verbal and visual memory ( ps < .05 ) . Memory was temporarily suppressed in the CCT group at T2 , but normalized by T3 . There was no effect of CCT on self-reported cognitive functioning , neurobehavioral functioning , nor quality of life . Conclusions This study provides tentative support for the feasibility and acceptability of CCT to treat mild cognitive impairment in ADT patients . CCT had a beneficial effect on reaction time , but temporarily suppressed memory . CCT ’s benefits may be limited to a narrow area of functioning . Larger-scale studies are needed Abstract Background Cognitive complaints are common amongst breast cancer survivors , and no st and ard treatment exists . The present study evaluates whether web‐based cognitive training can alleviate subjectively reported and objective ly assessed cognitive complaints in a sample of breast cancer survivors . The primary and secondary outcomes were an objective measure of working memory and a measure of perceived cognitive functioning . Additional outcomes were neuropsychological tests of memory , executive function , working memory and question naire‐based assessment of anxiety , depression and somatization . Methods A total of 157 female breast cancer survivors were recruited from an existing cohort and through announcements in open access cancer‐related Internet fora and r and omly allocated to either web‐based cognitive training ( eCogT ) with telephone support ( n = 94 ) or a waitlist control ( WLC ) condition ( n = 63 ) . eCogT encompassed 30 training sessions over 6 weeks . Neuropsychological assessment s were undertaken over the telephone , and question naire data was collected online . Data was collected at baseline , post‐intervention and at 5‐month follow‐up . Results Mixed linear models revealed no statistically significant change in primary or secondary outcome at follow‐up in either group . Statistically significant improvements ( p 0.040–0.043 ) were found in the eCogT group for verbal learning and on a working memory test . Conclusions Web‐based cognitive training did not result in improvements of the primary or secondary outcome . Improved performance was observed on verbal learning and working memory . These effects were observed at 5‐month follow‐up , indicating long‐term effects of training . The intervention may be applied in a clinical setting at low cost and without risk of adverse effects . © 2016 The Authors Psycho‐Oncology Published by John Wiley & Sons OBJECTIVE To evaluate the efficacy of a brief cognitive-behavioral therapy ( CBT ) that is being developed for management of cognitive dysfunction following chemotherapy among breast cancer survivors . Memory and Attention Adaptation Training ( MAAT ) is a brief CBT design ed to improve the quality of life and function among cancer survivors with post-chemotherapy cognitive complaints . METHODS An initial , two-group ( MAAT versus waitlist , no treatment control ) , r and omized clinical trial ( RCT ) was conducted . Forty stage I and II female breast cancer survivors ( mean age = 50 ; SD = 6.4 ) were r and omized to conditions and assessed at baseline , post-treatment ( 8 weeks ) and 2-month follow-up assessment points on measures of : ( 1 ) self-reported daily cognitive failures ; ( 2 ) quality of life ; and ( 3 ) neuropsychological performance . Participants were also assessed for satisfaction with MAAT . RESULTS With education and IQ as covariates , MAAT participants made significant improvements relative to controls on the spiritual well-being subscale of the quality of life measure and on verbal memory , but statistical significance was not achieved on self-report of daily cognitive complaints . However , moderate-to-large effect sizes were observed on these outcomes . Participants gave MAAT high satisfaction ratings . CONCLUSIONS Although this initial RCT is a small study , MAAT participants appear to improve on one measure of quality of life and verbal memory performance relative to no treatment controls and rate MAAT with high satisfaction . These data are encouraging and support the continued development and evaluation of MAAT efficacy Background . Interventions are needed to alleviate memory difficulty in cancer survivors . We previously showed in a phase III r and omized clinical trial that YOCAS © ® yoga — a program that consists of breathing exercises , postures , and meditation — significantly improved sleep quality in cancer survivors . This study assessed the effects of YOCAS © ® on memory and identified relationships between memory and sleep . Study design and methods . Survivors were r and omized to st and ard care ( SC ) or SC with YOCAS © ® . 328 participants who provided data on the memory difficulty item of the MD And erson Symptom Inventory are included . Sleep quality was measured using the Pittsburgh Sleep Quality Index . General linear modeling ( GLM ) determined the group effect of YOCAS © ® on memory difficulty compared with SC . GLM also determined moderation of baseline memory difficulty on postintervention sleep and vice versa . Path modeling assessed the mediating effects of changes in memory difficulty on YOCAS © ® changes in sleep and vice versa . Results . YOCAS © ® significantly reduced memory difficulty at postintervention compared with SC ( mean change : yoga=−0.60 ; SC=−0.16 ; P<.05 ) . Baseline memory difficulty did not moderate the effects of postintervention sleep quality in YOCAS © ® compared with SC . Baseline sleep quality did moderate the effects of postintervention memory difficulty in YOCAS © ® compared with SC ( P<.05 ) . Changes in sleep quality was a significant mediator of reduced memory difficulty in YOCAS © ® compared with SC ( P<.05 ) ; however , changes in memory difficulty did not significantly mediate improved sleep quality in YOCAS © ® compared with SC . Conclusions . In this large nationwide trial , YOCAS © ® yoga significantly reduced patient-reported memory difficulty in cancer survivors OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND A majority of breast cancer ( BC ) survivors , particularly those treated with chemotherapy , experience long-term cognitive deficits that significantly reduce quality of life . Among the cognitive domains most commonly affected include executive functions ( EF ) , such as working memory , cognitive flexibility , multitasking , planning , and attention . Previous studies in other population s have shown that cognitive training , a behavioral method for treating cognitive deficits , can result in significant improvements in a number of cognitive skills , including EF . MATERIAL S AND METHODS In this study , we conducted a r and omized controlled trial to investigate the feasibility and preliminary effectiveness of a novel , online EF training program in long-term BC survivors . A total of 41 BC survivors ( 21 active , 20 wait list ) completed the 48 session training program over 12 weeks . The participants were , on average , 6 years after therapy . RESULTS Cognitive training led to significant improvements in cognitive flexibility , verbal fluency and processing speed , with marginally significant downstream improvements in verbal memory as assessed via st and ardized measures . Self-ratings of EF skills , including planning , organizing , and task monitoring , also were improved in the active group compared with the wait list group . CONCLUSIONS Our findings suggest that EF skills may be improved even in long-term survivors by using a computerized , home-based intervention program . These improvements may potentially include subjective EF skills , which suggest a transfer of the training program to real-world behaviors CONTEXT After successful cancer treatment , a substantial number of survivors continue to experience fatigue and related concentration and memory problems . Severe fatigue after cancer treatment can be treated effectively with cognitive behavioral therapy ( CBT ) , but it is unclear whether CBT has an effect on cognitive functioning . OBJECTIVES We hypothesized that patients would report less cognitive disability after treatment with CBT for cancer-related fatigue . CBT was not expected to affect neuropsychological test performance , as it has been shown that fatigue is not associated with test performance . METHODS Data were used from a r and omized controlled trial in which 98 severely fatigued cancer survivors , treated at least one year previously , were assessed at baseline ( T1 ) and six months post-baseline ( T2 ) . Patients were r and omly assigned to receive CBT ( n = 50 ) or to a waiting list ( WL ) control condition ( n = 48 ) . Self-reported cognitive disability was assessed by the Concentration subscale of the Checklist Individual Strength and the Alertness Behavior subscale of the Sickness Impact Profile . Neuropsychological test performance was measured by the symbol digit modalities task and two reaction time tasks . RESULTS Patients who received CBT for post-cancer fatigue reported significantly less cognitive disability compared with those in the WL group . CBT also was associated with a clinical ly relevant reduction in concentration problems ( CBT , 32 % vs. WL , 2 % ) . There were no significant differences in neuropsychological test performance between the CBT and WL groups . CONCLUSION CBT for post-cancer fatigue has already been shown to be an effective therapy . The present study demonstrates that CBT also may lead to a decrease in perceived cognitive disability Long‐term chemotherapy‐related cognitive dysfunction ( CRCD ) affects a large number of cancer survivors . To the authors ' knowledge , to date there is no established treatment for this survivorship problem . The authors herein report results of a small r and omized controlled trial of a cognitive behavioral therapy ( CBT ) , Memory and Attention Adaptation Training ( MAAT ) , compared with an attention control condition . Both treatments were delivered over a videoconference device Purpose Cognitive impairment is reported frequently by cancer survivors . There are no proven treatments . We evaluated a cognitive rehabilitation program ( Insight ) and compared it with st and ard care in cancer survivors self-reporting cognitive symptoms . Patients and Methods We recruited adult cancer survivors with a primary malignancy ( excluding central nervous system malignancies ) who had completed three or more cycles of adjuvant chemotherapy in the previous 6 to 60 months and reported persistent cognitive symptoms . All participants received a 30-minute telephone consultation and were then r and omly assigned to the 15-week , home-based intervention or to st and ard care . Primary outcome was self-reported cognitive function ( Functional Assessment of Cancer Therapy Cognitive Function [ FACT-COG ] perceived cognitive impairment [ PCI ] subscale ) : difference between groups after intervention ( T2 ) and 6 months later ( T3 ) . Results A total of 242 participants were r and omly assigned : median age , 53 years ; 95 % female . The primary outcome of difference in FACT-COG PCI was significant , with less PCI in the intervention group at T2 ( P < .001 ) . This difference was sustained at T3 ( P < .001 ) . At T2 , there was a significant difference in all FACT-COG subscales , favoring the intervention . Neuropsychological results were not significantly different between the groups at T2 or T3 . There were significantly lower levels of anxiety/depression and fatigue in the intervention group at T2 . There were significant improvements in stress in the intervention group at both time points . There was no significant difference in quality of life between the groups at T2 , but the intervention group had better quality of life at T3 . Conclusion The intervention , Insight , led to improvements in cognitive symptoms compared with st and ard care . To our knowledge , this is the first large r and omized controlled trial showing an improvement in self-reported cognitive function in cancer survivors , indicating that this intervention is a feasible treatment AIMS The second most frequently reported post-treatment symptom in cancer survivors are concerns about impaired cognition . Despite numerous studies demonstrating significant impairments in a portion of survivors , information on effective treatments remains an emerging area of research . This study examined the effectiveness of a group-based cognitive rehabilitation intervention in cancer survivors . MAIN METHODS This study was a r and omized , controlled study of a 7-week cognitive rehabilitation intervention delivered in group format . Participants were evaluated with subjective symptom question naires and objective neurocognitive tests prior to and following treatment . KEY FINDINGS Twenty-eight participants ( mean age 58 years ) with a median of 3 years ( ± 6 years ) post- primary /adjuvant treatment and various cancer sites ( breast , bladder , prostate , colon , uterine ) completed the study . Compared to baseline , the treatment group demonstrated improvements in symptoms of perceived cognitive impairments ( p<.01 ) , cognitive abilities ( p<.01 ) and overall quality of life with regard to cognitive symptoms ( p<.01 ) as measured by the FACT-Cog . The treatment group also improved on objective measures of attention ( p<.05 ) and a trend toward improvement on verbal memory . Significant improvement was not observed on all cognitive tests . SIGNIFICANCE A group based cognitive rehabilitation intervention in cancer survivors was effective for improving attention abilities and overall quality of life related to cognition . Results suggest that group based cognitive rehabilitation may be an effective intervention for treating cognitive dysfunction in cancer patients and should be further studied in a larger trial with an active control condition Elderly cancer survivors report difficulty with attention , concentration , and memory . This study tested the effectiveness of the Cognitive Behavioral Model of Everyday Memory , an efficacy-based intervention design ed to improve memory performance , memory self-efficacy , and metamemory in older adult cancer survivors and those with other chronic conditions . The study provides interesting new evidence that the responses of a group of elders to training varies depending on their health status PURPOSE We conducted a r and omized clinical trial evaluating the efficacy of a cognitive rehabilitation ( CR ) intervention compared with a wait list ( WL ) control condition on cognitive complaints , neuropsychological and brain functioning in breast cancer survivors ( BCS ) . METHODS The small group intervention of five sessions included psychoeducation and cognitive exercises . ELIGIBILITY Disease-free BCS with cognitive complaints , diagnosed with stage I , II or III breast cancer , completed primary treatment 18 months to 5 years earlier . Neurocognitive test data and cognitive complaints on the Patient 's Assessment of Own Functioning Inventory ( PAOFI ) were assessed at baseline ( T1 ) , immediately post-intervention ( T2 ) , and 2 months later ( T3 ) . A subgroup of participants underwent resting state quantitative electroencephalography ( qEEG ) at all three assessment time points . RESULTS Forty-eight participants [ mean age ( SD ) 53.8 ( 8.2 ) ] completed T1 assessment s , and 29 participants had analyzable qEEG data . The CR group improved significantly over time compared with the WL group on PAOFI total and memory scores ( both p = .01 ) and on Rey Auditory Verbal Learning Test ( RAVLT ) total ( trials I-V ) ( p = .02 ) and RAVLT delayed recall ( p = .007 ) scores . On qEEG , the CR group showed a significant decrease in delta ' slow wave ' power ( p = .02 ) and an increase in the frontal distribution of alpha power ( p = .04 ) from T1 to T2 . CONCLUSIONS BCS in the CR group showed immediate and sustained improvements in self-reported cognitive complaints and memory functioning on neurocognitive testing . Results of the qEEG sub study provide some support for neurophysiological changes underlying the intervention . Copyright © 2015 John Wiley & Sons , Some breast cancer survivors experience cognitive decline following chemotherapy . We prospect ively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide , thiotepa , and carboplatin ( CTC group ; n = 28 ) or st and ard-dose chemotherapy with 5-fluorouracil , epirubicin , and cyclophosphamide ( FEC group ; n = 39 ) ; stage-I breast cancer patients who had received no systemic chemotherapy ( no-CT group ; n = 57 ) ; and healthy control subjects ( n = 60 ) . All patients underwent neuropsychologic testing before and 6 months after treatment ( 12-month interval ) ; control subjects underwent repeated testing over a 6-month interval . No differences in cognitive functioning between the four groups were observed at the first assessment . More of the CTC group than the control subjects experienced a deterioration in cognitive performance over time ( 25 % versus 6.7 % ; odds ratio [ OR ] = 5.3 , 95 % confidence interval [ CI ] = 1.3 to 21.2 , P = .02 ) . No such difference was observed for the FEC or the no-CT groups ( FEC versus control : OR = 2.2 , 95 % CI = 0.5 to 9.1 , P = .27 ; no-CT versus Control : OR = 2.2 , 95 % CI = 0.6 to 8.0 ; P = .21 ) . Some cytotoxic treatment for breast cancer affects cognition in a subset of women |
10,330 | 29,125,183 | AUTHORS ' CONCLUSIONS There was no clear evidence that LOD improves menstrual regularity or the and rogenic symptoms of PCOS , compared to most of the medical treatments used in the included studies .
LOD was associated with fewer gastrointestinal side effects compared to metformin and clomiphene .
There was also no clear evidence of different effectiveness between types of LOD , except that LOD with four to five punctures per ovary may be more effective than two or fewer punctures .
However , gonadotrophins are seldom used for this indication | BACKGROUND Polycystic ovary syndrome ( PCOS ) is a common endocrine condition , affecting approximately one in 10 women .
PCOS is defined by two of three features : oligo- or anovulation , clinical or biochemical hyper and rogenism or both , or polycystic ovaries .
Women with PCOS can have a wide range of health problems , including infrequent and irregular periods , unwanted hair growth and acne , and subnormal fertility .
Long-term health concerns include an increased risk of heart disease , diabetes and the development of precancerous disease of the womb .
OBJECTIVES To assess the effectiveness and harms of ovarian surgery as a treatment for symptomatic relief of hirsutism , acne and menstrual irregularity in PCOS . | Objectives Laparoscopic ovarian drilling ( LOD ) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome ( PCOS ) , with tubo-ovarian adhesion formation as the major disadvantage . Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling . Methods This prospect i ve r and omized study included 44 patients with anovulatory infertility due to PCOS . Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007 . The number of drilling site in each ovary was limited to five . The clinical and biochemical response , ovulation and pregnancy rates over a follow-up period of 1 year were compared . Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy . Results There was no statistical difference between the two groups in terms of clinical and biochemical response , ovulation rate and pregnancy rate . Postoperatively , tubo-ovarian adhesions could be assessed in 36.3 % of the patients and no adhesions were found in a single case in either group . Conclusion Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy . Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation OBJECTIVE To compare the hormonal-metabolic profiles and reproductive outcomes in clomiphene-resistant patients with polycystic ovary syndrome and insulin resistance between women receiving metformin and those undergoing laparoscopic ovarian drilling . METHODS A total of 110 eligible participants were r and omly allocated to diagnostic laparoscopy plus metformin therapy ( group 1 , n=55 ) or laparoscopic ovarian drilling ( group 2 , n=55 ) . The t test was used for mean comparisons of hormonal-metabolic parameters and OGTT values before and after treatment . The chi(2 ) test was used for comparisons of ovulation , pregnancy , and abortion rates . RESULTS Groups 1 and 2 showed a significant decline in testosterone , insulin-like growth factor-1 ( P<0.001 vs P<0.001 ) , and luteinizing hormone ( P<0.05 vs P<0.001 ) , while the glucose to insulin ratio was significantly increased ( P<0.001 vs P<0.05 ) compared with baseline . Group 2 patients had more regular cycles and higher rates of ovulation and pregnancy compared with group 1 : 76.4 % [ 42/55 ] vs 58.2 % [ 32/55 ] , P<0.04 ; 50.8 % [ 131/258 ] vs 33.5 % [ 94/281 ] , P<0.001 ; and 38.2 % [ 21/55 ] vs 20.0 % [ 11/55 ] , P<0.03 , respectively . The difference in the early abortion rate between the groups was not statistically significant . CONCLUSION Although metformin results in a better attenuation of insulin resistance , laparoscopic ovarian drilling is associated with higher rates of ovulation and pregnancy The aim of the present study was to compare the reproductive outcomes of letrozole and laparoscopic ovarian drilling ( LOD ) in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome ( PCOS ) . A total of 141 women with CC-resistant PCOS were enrolled and r and omly allocated into groups A and B. Group A ( n=71 ) received 2.5 mg letrozole from days 5 to 10 of menses for up to six cycles , and group B ( n=70 ) underwent LOD . A 6-month follow-up was performed . No statistically significant difference was found in the baseline clinical characteristics and the major serum hormone profiles , including luteinizing hormone , follicle-stimulating hormone , estradiol and free testosterone , between the two groups . Women receiving letrozole had a lower rate of spontaneous abortion ( 6.9 vs. 15.8 % ) and higher clinical pregnancy ( 40.8 vs. 27.1 % ) and live birth ( 38.0 vs. 22.9 % ) rates ; however , the differences were not statistically significant . Letrozole had superior reproductive outcomes compared with LOD in women with CC-resistant PCOS ; therefore , letrozole could be used as the first-line treatment for women with CC-resistant PCOS Objectives Rosiglitazone , an insulin sensitizing agent is used currently in women with clomiphene citrate ( CC ) resistant polycystic ovarian syndrome ( PCOS ) . Our study proposed to compare the efficacy of rosiglitazone and CC with laparoscopic ovarian drilling ( LOD ) and CC in terms of biochemical effects , ovulation rate and pregnancy rate in patients of PCOS resistant to CC . Methods This prospect i ve r and omised trial included 43 patients of PCOS resistant to CC . Twenty-two women were assigned to the rosiglitazone ( 4 mg twice daily ) and CC group and other 21 patients underwent unilateral LOD and then received CC and multivitamins . The treatment continued for six cycles in both the groups . The biochemical response , ovulation rate and pregnancy rate over a follow up period of 6 months were compared . Results Treatment with rosiglitazone and CC or LOD and CC result ed in increased ovulation ( 80.8 vs. 81.5 % ) and pregnancy ( 50 vs. 42.8 % ) , respectively . There was no statistical difference between the two groups in terms of biochemical response , ovulation rate and pregnancy rate . Conclusion To avoid the risk of adverse effects of LOD preference may be given to the use of rosiglitazone and CC therapy in patients of PCOS resistant to CC BACKGROUND Laparoscopic ovarian diathermy ( LOD ) is currently accepted as a successful second-line treatment for ovulation induction ( OI ) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome ( PCOS ) . The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment . METHODS The study included 72 anovulatory women with PCOS who were r and omized to LOD ( n = 36 ) or CC ( n = 36 ) . Women who remained anovulatory after LOD were offered CC . Similarly , women receiving CC who failed to ovulate or conceive were offered LOD . Pregnancy rates were compared between the two groups using chi(2 ) and odds ratio with 95 % confidence interval ( OR , 95 % CI ) . RESULTS After r and omization , six women conceived before starting treatment and another patient postponed treatment . The remaining 65 women received the treatment ( 33 underwent LOD and 32 received CC ) . After the primary treatment , more pregnancies ( 44 % ) occurred in women receiving CC than in those undergoing LOD ( 27 % ) , although the difference did not reach statistical significance [ P = 0.13 , OR 2.1 ( 0.7 - 5.8 ) ] . After adding the second treatment , the pregnancy rate was still higher , but to a less extent , in the CC group [ 63 % versus 52 % , P = 0.2 , OR 1.6 ( 0.6 - 4.2 ) ] . CONCLUSIONS LOD is not superior to CC as a first-line method of OI in women with PCOS . The trial is registered with Clinical Trials.gov with an identifier number NCT00220545 OBJECTIVE To assess pain control in patients with polycystic ovary syndrome ( PCOS ) who are undergoing ovarian drilling during minilaparoscopy under local anesthesia and conscious sedation and to evaluate the efficacy of this protocol compared with the traditional approach in terms of operative and discharge times , subsequent ovulation , and pregnancy . DESIGN Prospect i ve r and omized study . SETTING University hospitals and private day-surgery unit . PATIENT(S ) Sixty-two infertile women with PCOS . INTERVENTION(S ) Group A underwent minilaparoscopic ovarian drilling under local anesthesia and conscious sedation . Group B ( control group ) was treated with traditional ovarian drilling by laparoscopy under general anesthesia . MAIN OUTCOME MEASURE(S ) Intraoperative pain score in group A. Hormonal profile before and after surgery , operative and discharge times , postoperative analgesic requirements , and reproductive follow-up in both groups . RESULT ( S ) Group A showed a good intraoperative pain score . The hormonal profile after surgery did not differ between groups A and B. Operative times were also similar for both groups . The number of patients discharged within 2 hours after surgery was significantly higher in group A. The need for postoperative analgesics was significantly higher in group B. No statistically significant differences were noted between the groups in terms of pregnancy and ovulation rates . CONCLUSION ( S ) Intraoperative and postoperative local anesthesia plus conscious sedation allows outpatient bilateral ovarian drilling by minilaparoscopy to be performed without general anesthesia . The high pregnancy rates , the simplicity of the method , and the faster discharge time offer a new option for patients with PCOS who are resistant to clomiphene citrate . Moreover , ovarian cauterization can be performed simultaneously with a diagnostic minilaparoscopy and integrated into the infertility workup of these patients This study was conducted to evaluate the efficacy of metformin compared with ovarian drilling in the treatment of clomiphene citrate ( CC ) resistant women with polycystic ovary syndrome . A total of 161 infertile , CC-resistant women with PCOS aged 22 - 34 years ( mean 25.5 ± 4.4 ) were evaluated prospect ively during the period between January 2000 and December 2001 . Patients were allocated into two groups ; group 1 includes 64 women who received metformin , 850 mg twice daily throughout the cycle , and group 2 which includes 97 women who underwent laparoscopic ovarian drilling . If spontaneous ovulation or pregnancy was not achieved within 3 months after treatment , CC was added with increments of 50 mg ( up to 150 mg/day ) for both groups . Clinical and menstrual characteristics in addition to the hormonal profile were evaluated before and after the treatment . There were no significant differences between the two groups in terms of age , body weight , BMI , duration of infertility and serum hormone levels ( and rogens , gonadotrophins , insulin ) before starting the treatment . A significant improvement in the regularity of menstrual cycles ( P<0.05 ) and a significant reduction in the serum levels of testosterone ( P<0.01 ) , and rostenedione ( P<0.01 ) , DHEAS ( P<0.05 ) , LH ( P<0.01 ) and LH : FSH ratio ( P<0.05 ) were noted after the treatment . There were no significant differences between the metformin group compared with the drilling group in the rates of ovulation ( 79.7 % vs. 83.5 % ) and pregnancy ( 64.1 % vs. 59.8 % ) . It is concluded that CC-resistant patients with polycystic ovary syndrome can be treated effectively either by metformin or by laparoscopic ovarian drilling . Menstrual cycle pattern and the rates of ovulation and pregnancy are improved significantly , due most probably to the significant decrease in the levels of and rogens and luteinising hormone Purpose To compare the effect of letrozole with laparoscopic ovarian diathermy ( LOD ) for ovulation induction in clomiphene citrate ( CC ) resistant women with polycystic ovary syndrome ( PCOS ) . Methods Two hundred and sixty anovulatory women with CC-resistant PCOS were selected in this r and omized controlled trial . Group A ( n = 128 ) received 2.5 mg letrozole daily for 5 days for up to six cycles . Group B ( n = 132 ) underwent LOD with 6 months follow-up . Outcome measures were ovulation rate , midcycle endometrial thickness , pregnancy , miscarriage and live birth rates . Results Ovulation occurred in 335/512 cycles ( 65.4 % ) in letrozole group and 364/525 cycles ( 69.3 % ) in LOD group without significant difference between both groups . Resumption of regular menstruation was similar in both treatment groups . A significant increase in midcycle endometrial thickness was observed in letrozole group ( 8.8 ± 1.1 mm vs. 7.9 ± 1.2 mm ) ( P < 0.05 ) . Pregnancy rate was similar in both groups ( 15.6 vs. 17.5 % ) . There were no statistical significant differences as regards miscarriage and live birth rates between both groups . No multiple pregnancy or ovarian hyperstimulation occurred in either group . Conclusion Letrozole and LOD are equally effective for inducing ovulation and achieving pregnancy in CC-resistant PCOS patients AIM To evaluate the biochemical , clinical and reproductive results after laparoscopic ovarian drilling that carried out a different number of punctures in the ovaries . METHODS Sixty-three clomiphene-citrate-resistant women with polycystic ovary syndrome ( PCOS ) underwent laparoscopic ovarian drilling using insulated needle cautery . Patients were allocated to two groups : group I ( n = 26 ) had five punctures per ovary , and group II ( n = 37 ) had 10 punctures per ovary . Biochemical and clinical data , before and after the procedure along with the reproductive outcome , were compared between the two groups . RESULTS There were no significant differences in terms of body mass index , and insulin and glucose levels before and after the procedure between the two groups . And rogen levels and luteinizing hormone concentrations showed a statistically significant decrease after the treatment . The clinical and reproductive outcome , including menses cyclicity , ovulation , and pregnancy rates were similar in both groups . CONCLUSION Laparoscopic ovarian drilling is an effective treatment in clomiphene-citrate-resistant women with PCOS . Five , instead of > or = 10 , punctures per ovary are sufficient to ameliorate the hyper and rogenic status in these women , improving their clinical and reproductive outcome OBJECTIVE To explore an optimal laser dose of transvaginal ultrasound-guided ovarian interstitial laser coagulation in management of anovulation in patients with polycystic ovary syndrome ( PCOS ) . DESIGN R and omized , controlled trial . SETTING A reproductive medical center . PATIENT(S ) Eighty women with PCOS and clomiphene citrate-resistant infertility underwent ultrasound-guided transvaginal ovarian interstitial yttrium aluminum garnet laser treatment . All subjects were divided r and omly into four groups of A , B , C , and D. INTERVENTION(S ) Group A , one coagulation point per ovary ; group B , two points ; group C , three points ; group D , four to five points . MAIN OUTCOME MEASURE(S ) Postoperative ovulation rate , pregnancy rate , and some biochemical parameters . RESULT ( S ) The rates of ovulation in groups C ( 75.00 % , 95 % confidence interval [ CI ] : 51%-91 % ) and D ( 80.00 % , 95 % CI : 56%-94 % ) within 6 postoperative months were significantly higher than in groups A ( 5.00 % , 95 % CI : 0%-25 % ) and B ( 15.00 % , 95 % CI : 3%-38 % ) . The pregnancy rates in groups C ( 45.00 % , 95 % CI : 23%-69 % ) and D ( 40.00 % , 95 % CI : 19%-64 % ) also were significantly higher than in groups A ( 5.00 % , 95 % CI : 0 - 25 % ) and B ( 10.00 % , 95 % CI : 1%-32 % ) . The mean serum T levels were significantly lower in groups C ( 2.08 + /- 0.62 nmol/L ) and D ( 2.07 + /- 0.42 nmol/L ) compared with groups A ( 3.10 + /- 0.63 nmol/L ) and B ( 2.95 + /- 0.63 nmol/L ) . CONCLUSION ( S ) One and two intraovarian laser coagulation points per ovary are associated with poor outcomes . Three points per ovary seem to represent the plateau of effective dose for the ovarian interstitial laser treatment in PCOS OBJECTIVE To evaluate the endocrinologic profile and reproductive outcome after laparoscopic drilling using a harmonic scalpel for polycystic ovarian syndrome ( PCOS ) in clomiphene-resistant infertile women . STUDY DESIGN We performed a prospect i ve , r and omized study of 34 infertile women with PCOS . Group A ( 17 women ) underwent laparoscopic ovarian drilling using a harmonic scalpel laser . Group B ( control group , 17 women ) underwent laparoscopic ovarian drilling using a neodymium-yttrium-aluminum-garnet laser . Change in the hormonal profile after surgery , ovulation rate and pregnancy rate were compared between groups A and B. RESULTS LH and testosterone serum levels and the LH-FSH ratio showed a statistically significant reduction after surgery , and the spontaneous ovulation rate was 94 % in both groups . The cumulative pregnancy rates within two years of follow-up were 77 % in group A and 60 % in group B. CONCLUSION Laparoscopic ovarian drilling using a harmonic scalpel is an effective treatment for PCOS in clomiphene-resistant , anovulatory women : it results in ovulation and conception without major complications This prospect i ve , r and omized study included 18 polycystic ovarian syndrome ( PCOS ) patients with severe ovarian dysfunction , who were evaluated by st and ard clomiphene and FSH stimulation . In this group of patients , a 6 month down-regulation with gonadotrophin-releasing hormone ( GnRH ) analogues gave outcomes similar to laparoscopic ovarian laser diathermy with respect to stimulatory outcome and pregnancy rate . Clomiphene stimulation with 50 mg of clomiphene/day and FSH stimulation in a low-dose , step-up protocol with purified FSH did not result in oligofollicular development ; thus patients were divided into two subgroups : one subgroup received laparoscopic laser drilling and the other received 6 months of therapy with GnRH analogues plus add-back therapy after diagnostic laparoscopy . Subsequently , three cycles of low-dose , step-up stimulation with recombinant FSH were started . In both groups , approximately 30 % of cycles still remained anovulatory . In the down-regulated subgroup , this mainly happened in the first cycle . In each group , ovulation was achieved in 14 cycles , intrauterine insemination was performed , and five pregnancies were obtained . This result ed in a pregnancy rate of 36 % per ovulatory cycle in both groups . Overall , 50 % of the formerly unreactive patients in both groups overcame childlessness . In achieving this , long-term treatment with GnRH analogues was as successful as laparoscopic laser diathermy Purpose Laparoscopic ovarian diathermy ( LOD ) represents a successful treatment option for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome ( PCOS ) . However , in case of CC failure PCOS , LOD offers several theoretical advantages . This study was conducted to compare the efficacy of LOD versus continuation of CC up to six further cycles in PCOS patients who failed to achieve pregnancy despite the previous successful CC induced ovulation . Methods One hundred and seventy six infertile women with CC failure PCOS were selected in this r and omized controlled trial . Patients ( n = 87 ) underwent LOD with 6 months follow-up or received CC ( n = 89 ) up to six cycles . Outcome measures were ; clinical pregnancy rate , midcycle endometrial thickness , cycle length , miscarriage and live birth rates . Results The clinical pregnancy rate per patient and the cumulative pregnancy rate after six cycles were comparable in both groups ( 39 vs. 33.7 % and 47 vs. 39.2 % , respectively ) . Four twin pregnancies occurred in CC group and none in LOD group and the difference was statistically significant ( p < 0.05 ) . No significant difference in midcycle endometrial thickness was observed ( 8.8 ± 1.2 mm vs. 7.7 ± 1.1 mm ) . Improvement in cycle length , miscarriage and live birth rates were comparable in both groups . No cases of ovarian hyperstimulation syndrome occurred in either group . Conclusions LOD during the 6 months follow-up period and CC for up to six further cycles are equally effective for achieving pregnancy in CC failure PCOS patients OBJECTIVE To study the effects of laparoscopic ovarian cauterization and combination of long-acting GnRH agonist ( GnRH-a ) and oral contraceptive ( OC ) therapy on endocrine changes in women with clomiphene citrate (CC)- resistant polycystic ovary disease ( PCOD ) . DESIGN Prospect i ve , r and omized . SETTING University-based infertility clinic . PATIENTS Seventeen women with CC-resistant PCOD were included r and omly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months . MAIN OUTCOME MEASURES Serum concentrations of LH , FSH , and rostenedione ( A ) , T , and sex hormone-binding globulin ( SHBG ) were determined before each therapeutic approach and during the follicular phase of first menstrual cycle after the cessation of each treatment . RESULTS The mean serum concentrations and the clinical profiles were similar in both groups . Both groups showed significant changes in LH , FSH , A , T , and SHBG compared with pretreatment levels . There were no significant differences in the final concentrations of LH , FSH , and A between the two study groups after each treatment , whereas T and SHBG levels were significantly different in the goserelin and OC group . The decrease in LH and increase in SHBG serum concentrations were greater in the goserelin and OC-treated women [ -59 % and + 5.9 % versus - 70 % and + 13.5 % , respectively ] . Although the SHBG concentration increased in both groups , the serum SHBG concentration of the goserelin and OC group was significantly higher than the other group . CONCLUSION Both therapeutic modalities revealed similar effects on the endocrine profiles in women with CC-resistant PCOD . Considering the invasiveness , cost , and potential complications of laparoscopic ovarian cauterization , noninvasive medical treatment with GnRH-a and OC combination may be more effective in restoring the optimal follicular environment in women with PCOD OBJECTIVE To compare hormone levels and clinical outcomes in patients with polycystic ovary syndrome ( PCOS ) after metformin therapy or laparoscopic ovarian diathermy ( LOD ) at 6 months follow-up . METHODS A r and omized trial was conducted in 126 patients with PCOS who had a history of infertility for at least 1 year and resistance to clomiphene citrate ( CC ) . Patients ( n=63 ) received metformin treatment or underwent LOD ( n=63 ) . RESULTS Levels of follicle-stimulating hormone did not change in either group after the intervention ( P>0.05 ) . Serum levels of testosterone ( P<0.001 ) and luteinizing hormone ( P<0.001 ) were significantly lower after the treatment in both groups . The proportion of women with regular menstrual cycles increased significantly to 35 % ( P<0.001 ) in the LOD group and to 49 % ( P<0.001 ) in metformin group compared with before the intervention . Although proportion was higher in the metformin group compared with the LOD group , the difference was not significant ( odds ratio 1.81 ; 95 % CI , 0.88 - 3.69 , P=0.1 ) . Hirsutism decreased significantly from 100 % to 79.37 % ( P<0.001 ) in both groups . CONCLUSION CC-resistant patients with PCOS were treated effectively by both metformin and LOD OBJECTIVE To compare the effectiveness of laparoscopic ovarian diathermy with gonadotropin ovulation induction for women with clomiphene citrate-resistant polycystic ovary syndrome . DESIGN R and omized controlled trial . SETTING A tertiary referral fertility clinic . PATIENT(S ) Women with anovulatory infertility secondary to clomiphene-resistant polycystic ovary syndrome . Inclusion criteria were age of < 39 years , body mass index of < 35 kg/m(2 ) , failure to ovulate with 150 mg of clomiphene citrate for 5 days in the early follicular phase , > 12 months of infertility , and no other causes of infertility . INTERVENTION(S ) Laparoscopic ovarian diathermy versus three cycles of urinary or recombinant gonadotropins . MAIN OUTCOME MEASURE(S ) Cumulative pregnancy and miscarriage rates . RESULT ( S ) Cumulative pregnancy rates were 28 % at 6 months for laparoscopic ovarian diathermy and 33 % for three cycles of ovulation induction with gonadotropins . There were three miscarriages in each group . Women in the laparoscopic ovarian diathermy arm of the study had four additional spontaneous pregnancies 6 to 12 months after surgery . CONCLUSION ( S ) There was no statistically significant difference in pregnancy or miscarriage rates during the 6-month follow-up period or the three cycles . Laparoscopic ovarian diathermy is a safe and effective alternative to ovulation induction with gonadotropins OBJECTIVE To compare reproductive outcome of adjusted thermal dose on the basis of ovarian volume versus fixed-puncture dosage in laparoscopic ovarian drilling . DESIGN R and omized controlled trial . SETTING University Women 's Health Center . PATIENT(S ) One hundred twenty patients with polycystic ovary syndrome and clomiphene citrate resistance . INTERVENTION(S ) Patients were assigned r and omly to two groups of 60 women each . Group A received an adjusted thermal dose based on ovarian volume with use of a new model for dose calculation ( 60 J/cm(3 ) of ovarian tissue ) , and group B received 600 J per ovary through four ovarian holes regardless of size . One month afterward , the hormonal profile was reevaluated , and second-look laparoscopy was performed in patients who had not conceived by 6 months to evaluate adnexal adhesions . MAIN OUTCOME MEASURE(S ) Ovulation , conception , and early abortion rates , cycle rhythm , and adnexal adhesions . RESULT ( S ) More patients resumed regular cycles in group A than in group B ( 87.9 % vs. 75.4 % ) . The ovulation and pregnancy rates were significantly higher in group A than in group B ( 81.8 % vs. 62.2 % and 51.7 % vs. 36.8 % , respectively ) . There was no significant difference between groups in early miscarriage rate or postdrilling adhesions . CONCLUSION ( S ) Adjusted diathermy dose based on ovarian volume for laparoscopic ovarian drilling of polycystic ovary syndrome has a better reproductive outcome compared with fixed thermal dosage OBJECTIVE To evaluate the effect of laparoscopic ovarian drilling ( LOD ) on plasma levels of anti-Müllerian hormone ( AMH ) and ovarian stromal blood flow changes , by using three-dimensional power Doppler ultrasonography , in polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve controlled study . SETTING Taiba hospital , Kuwait . PATIENT(S ) Twenty-three anovulatory clomiphene citrate (CC)-resistant women with PCOS and 20 fertile women as a control group . INTERVENTION(S ) Laparoscopic ovarian drilling . MEAN OUTCOME MEASURE(S ) Serum levels of AMH , ovarian three-dimensional power Doppler indices ( vascularization index , flow index , and vascularization flow index ) and occurrence of ovulation or pregnancy . RESULT ( S ) Plasma AMH and power Doppler indices of ovarian stromal blood flow were significantly higher in the PCOS group than in the control group . Plasma AMH and ovarian stromal blood flow Doppler indices were significantly reduced in the PCOS group after LOD . Women who ovulated after LOD had a significantly lower preoperative AMH compared with the nonresponders . There was a significant positive correlation between AMH and power Doppler flow indices before and after LOD in PCOS group . CONCLUSION ( S ) Measuring AMH and ovarian stromal three-dimensional power Doppler blood flow for women with anovulatory PCOS undergoing LOD may provide a useful tool in evaluating the outcome of LOD Abstract Objective To compare the therapeutic effects of metformin ( Met ) and laparoscopic ovarian drilling ( LOD ) in clomiphene and insulin-resistant patients with polycystic ovary syndrome ( CIRPCOS ) . Methods A total of 110 patients were r and omly divided into two groups . One group was administered Met ( n = 55 ) , while the other group underwent LOD ( n = 55 ) . Rates of ovulation , pregnancy , and abortion were compared between both groups . Results Rates of normal menstruation , ovulation , and pregnancy in the LOD group were higher than in the Met group : 76.4 % ( 42/55 ) vs. 58.2 % ( 32/55 ) , P < 0.04 ; 50.8 % ( 11/258 ) vs. 33.5 % ( 94/281 ) , P < 0.001 ; 38.2 % ( 21/55 ) vs. 20.0 % ( 11/55 ) , P < 0.03 . The difference in the early abortion rate between both groups was not statistically significant . Conclusions Although Met can significantly improve a patient ’s insulin resistance , we found that in patients diagnosed with CIRCPOS , LOD can be much more effective in improving rates of normal menstruation , ovulation , and pregnancy OBJECTIVE To evaluate the outcome of ovarian needle drilling using transvaginal ultrasound guidance as an alternative to the traditional laparoscopic electrosurgical drilling for patients with polycystic ovary syndrome ( PCOS ) . DESIGN A r and omized controlled study . SETTING University teaching hospital and private practice setting . PATIENT(S ) The study comprised 163 patients with clomiphene-resistant PCOS . INTERVENTION(S ) Patients were r and omly allocated to either treatment with ultrasound-guided transvaginal needle ovarian drilling ( UTND ; n = 82 ) or laparoscopic electrosurgery ovarian drilling ( n = 81 ) . MAIN OUTCOME MEASURE(S ) Hormonal changes ( FSH , LH , T ) , ovulation and pregnancy . RESULT ( S ) There were no significant differences between the two groups with regard to body mass index , hormonal profiles , clinical manifestations , and ultrasound findings of PCOS . The duration of UTND was 15.3 + /- 5.61 minutes ( 10.5 - 22.3 minutes ) , while it was 25.6 + /- 8.2 minutes ( 20.3 - 38.1 minutes ) in laparoscopic drilling , with a statistically significant difference between the two groups . There were no significant differences between the two groups with regard to resumption of normal menstruation , hirsutism , acne , ovulation , and pregnancy . UTND result ed in significant improvement in the ovulation , pregnancy , hirsutism , and acne . There were significant decreases in the serum LH and T levels but not in the FSH or LH/FSH levels after UTND as well . CONCLUSION ( S ) UTND can be adopted as an outpatient office procedure . The ease of scheduling , reduced costs , and rapid recovery suggest it as a first-line treatment for PCOS cases resistant to clomiphene citrate AIM To compare the effect of combined metformin and clomiphene citrate ( CC ) with laparoscopic ovarian diathermy ( LOD ) meant for ovulation induction in CC-resistant women with polycystic ovary syndrome ( PCOS ) . METHODS Two-hundred and eighty-two anovulatory women with CC-resistant PCOS were selected in this r and omized controlled trial . Patients ( n = 138 ) received combined metformin-CC for up to six cycles or underwent LOD ( n = 144 ) with six months follow up . The outcome measures were : ovulation rate , midcycle endometrial thickness , pregnancy and miscarriage rates . RESULTS Ovulation occurred in 386/576 cycles ( 67 % ) in the combined metformin-CC group and 381/558 cycles ( 68.2 % ) in LOD group without a significant difference between the groups . Resumption of regular menstruation was similar in both groups . A significant increase in midcycle endometrial thickness was observed in the combined metformin-CC group ( 9.2 ± 1.2 mm vs 7.6 ± 1.1 mm ) ( P < 0.05 ) . The pregnancy rate was similar in both groups ( 15.4 % vs 17 % ) , and there were no statistically significant differences regarding the miscarriage rate between both groups . Four twin pregnancies occurred in the metformin-CC group . No ovarian hyperstimulation occurred in either group . CONCLUSIONS Combined metformin-CC and LOD are equally effective for inducing ovulation and achieving pregnancy in CC-resistant PCOS patients Abstract Objective : To assess the impact of unilateral dose adjusted ovarian drilling ( ULOD ) compared to bilateral ovarian drilling ( BLOD ) on ovarian reserve and pregnancy rate . Methods : This r and omized clinical study included 105 patients with polycystic ovary syndrome . Patients were assigned to two groups ; group 1 ( n = 52 ) underwent dose adjusted ULOD using 60 Joules/cm3 applied to the larger ovary , while group 2 ( n = 53 ) underwent BLOD with fixed doses of 1200 J. Ovulation rate , anti-Mullerian hormone ( AMH ) , antral follicle count ( AFC ) , and pregnancy rates were assessed at 3 and 6 months of follow-up . Results : Ovulation and pregnancy rates at 3 months periods were comparable ( p > 0.05 ) , but was significantly higher in BLOD at 6 months period ( p < 0.05 ) . There was a highly significant difference between the two groups regarding the AMH level at 3- and 6-month follow-up periods ( p < 0.001 ) with lower levels in the BLOD group . The AFC was comparable in the two groups after 3 months ( p > 0.05 ) but became higher in the ULOD at 6-month follow-up period ( p < 0.001 ) . Conclusion : Dose-adjusted ULOD applied to the larger ovary has comparable ovulation and pregnancy rates to fixed dose BLOD at 3-month follow-up periods with decrease in its effectiveness after 6 months Purpose To compare conventional laparoscopic ovarian drilling ( LOD ) with transvaginal hydrolaparoscopy ( THL ) ovarian drilling in terms of ovarian adhesion formation , evaluated using office THL during follow-up in CC-resistant anovulatory patients affected by PCOS . Methods Prospect i ve r and omized study on 246 CC-resistant women with PCOS . The patients enrolled were divided into two groups , 123 were scheduled to undergo LOD and 123 to undergo THL ovarian drilling . Six months after the procedure all patients were offered office transvaginal hydrolaparoscopy ( THL ) follow-up , under local anesthesia to evaluate adhesion formation . Results Duration of the procedure was significantly shorter in the THL group in comparison with LOD group ( p < 0.0001 ) . No intra- or post-operative complication was observed in any of the patients in both groups . Post-operative THL follow-up after 6 months showed that 15 ( 15.5 % ) patients in the THL group and 73 ( 70.2 % ) in the LOD group showed the presence of ovarian adhesion . This difference was highly significant with a p value < 0.0001 and a relative risk of 0.22 [ 95 % IC 0.133–0.350 ] . Conclusion This study seems to indicate that THL ovarian drilling may reduce the risk of ovarian adhesion formation and could be used as a safe and effective option to reduce ovarian adhesion formation in patients undergoing ovarian drilling Ovarian drilling is a well-accepted intervention for ovulation induction in clomiphene citrate-resistant polycystic ovarian syndrome ( PCOS ) patients . The aim of this study was to evaluate the effect of unilateral and bilateral ovarian drilling by electrocautery in PCOS women . In this prospect i ve r and omized clinical study , 87 patients with ovulation failure as a result of PCOS were r and omly allocated to either unilateral ( group A ; n = 43 patients ) or bilateral ( group B ; n = 44 patients ) laparoscopic ovarian drilling by electrocautery . The average time required for unilateral ovarian drilling was shorter than for bilateral drilling . In patients who ovulated after drilling , there was a significant fall in serum LH concentration ( group A , P < 0.05 , group B , P < 0.05 ) . Ovulation , pregnancy and miscarriage rates were similar in both groups . It seems that unilateral ovarian drilling in PCOS is effective , less time-consuming and probably associated with fewer complications Laparoscopic ovarian drilling ( LOD ) is the accepted second-line treatment for clomiphene citrate-resistant anovulatory infertility in polycystic ovary syndrome ( PCOS ) . Although multiple pregnancy rates are reduced with ovarian drilling procedures , postoperative adhesion formation is a potential complication in up to 85 % of the women subjected to laparoscopic destructive ovarian procedures . Our objective was to determine the effectiveness of a new , specially design ed laparoscopic device and technique that might enable treatment for patients with anovulatory PCOS with less trauma and fewer postoperative adhesions . Thirty-five infertile clomiphene citrate-resistant women with PCOS were included . Seventeen women underwent laparoscopic ovarian multi-needle intervention ( LOMNI ) , and 18 women received step-up ovulation induction treatment with recombinant follicle-stimulating hormone followed by intrauterine insemination for three cycles . Patients were followed for a period of 6 months after either laparoscopic surgery or the initiation of ovulation induction therapy . Outcome measures were cycle regularity , pregnancy rate , safety , postoperative adhesion formation , and cost effectiveness . There were no significant differences between the two groups in terms of age , body-mass index , duration of infertility , and basal cycle-day 2 hormone levels . Significant improvement in cycle regularity ( p < .01 ) was found after LOMNI . Cumulative pregnancy rates ( 35.3 % in the LOMNI group vs 33.3 % in the ovulation induction group ) did not differ between the groups . No adverse events following surgery were noted . Moderate ovarian hyperstimulation syndrome and multiple pregnancies occurred in four and two patients , respectively , in the ovulation induction group . Eight nonpregnant women in the LOMNI group underwent repeat laparoscopy at the end of the follow-up period . No adhesion formation attributable to LOMNI was observed in any of those eight women . The cost of LOMNI was significantly ( p < .001 ) lower than the ovulation induction treatment . In conclusion , LOMNI may be a safe , inexpensive , and effective procedure for the treatment of CC-resistant infertility in patients with PCOS . It seems to preserve the beneficial effects and probably omits unwanted effects ( such as adhesion formation ) of LOD OBJECTIVE The purpose of this study was to compare the effectiveness of laparoscopic ovarian diathermy ( LOD ) vs clomiphene citrate ( CC ) plus metformin in infertile patients with CC-resistant polycystic ovary syndrome ( PCOS ) . STUDY DESIGN Fifty primary infertile patients with CC-resistant PCOS were assigned r and omly to receive LOD followed by a 6-month observation ( group A ) or 6-cycle course of CC plus metformin ( group B ) . Reproductive and safety outcomes were analyzed . RESULTS No significant difference between 2 groups in pregnancy ( 15/92 women [ 16.3 % ] vs 14/107 women [ 13.1 % ] ; P = .521 ) and live-birth ( 13/92 women [ 14.1 % ] vs 12/107 women [ 11.2 % ] ; P = .536 ) rates per cycle was observed . With the use of a Cox regression analysis , patients under medical treatment , compared with patients who received surgical treatment , had a relative risk of pregnancy of 1.2 ( 95 % confidence interval , 0.61 - 2.44 ; P = .582 ) and a relative risk of live-birth of 1.4 ( 95 % confidence interval , 0.63 - 2.96 ; P = .425 ) . CONCLUSION LOD and CC plus metformin seem to be 2 effective approaches to treat infertility in patients with CC-resistant PCOS |
10,331 | 27,779,777 | DISCUSSION Positive results changing intentions would lead to a r and omized controlled trial of the behaviour change intervention in clinical practice , assessing patient delay in the event of actual symptoms . | AIMS To evaluate the efficacy of a behaviour change technique-based intervention and compare two possible modes of delivery ( text + visual and text-only ) with usual care .
BACKGROUND Patient delay prevents many people from achieving optimal benefit of time-dependent treatments for acute coronary syndrome .
Reducing delay would reduce mortality and morbidity , but interventions to change behaviour have had mixed results .
Systematic inclusion of behaviour change techniques or a visual mode of delivery might improve the efficacy of interventions . | Background —Delay from onset of acute coronary syndrome ( ACS ) symptoms to hospital admission continues to be prolonged . To date , community education campaigns on the topic have had disappointing results . Therefore , we conducted a clinical r and omized trial to test whether an intervention tailored specifically for patients with ACS and delivered one-on-one would reduce prehospital delay time . Methods and Results — Participants ( n=3522 ) with documented coronary heart disease were r and omized to experimental ( n=1777 ) or control ( n=1745 ) groups . Experimental patients received education and counseling about ACS symptoms and actions required . Patients had a mean age of 67±11 years , and 68 % were male . Over the 2 years of follow-up , 565 patients ( 16.0 % ) were admitted to an emergency department with ACS symptoms a total of 842 times . Neither median prehospital delay time ( experimental , 2.20 versus control , 2.25 hours ) nor emergency medical system use ( experimental , 63.6 % versus control , 66.9 % ) was different between groups , although experimental patients were more likely than control to call the emergency medical system if the symptoms occurred within the first 6 months following the intervention ( P=0.036 ) . Experimental patients were significantly more likely to take aspirin after symptom onset than control patients ( experimental , 22.3 % versus control , 10.1 % , P=0.02 ) . The intervention did not result in an increase in emergency department use ( experimental , 14.6 % versus control , 17.5 % ) . Conclusions —The education and counseling intervention did not lead to reduced prehospital delay or increased ambulance use . Reducing the time from onset of ACS symptoms to arrival at the hospital continues to be a significant public health challenge . Clinical Trial Registration — clinical trials.gov . Identifier NCT00734760 Background There has been increasing interest in the ability of the internet to produce behaviour change . The focus of this study was to describe program exposure across three intervention groups from a r and omised trial ( RT ) comparing traditional face-to-face , internet-mediated ( combined internet plus face-to-face ) , and internet-only program delivery . Methods Baseline and immediately post-intervention survey data , and exposure rates from participants that commenced the RT were included ( n = 192 ) . Exposure was defined as either face-to-face attendance , website usage , or a combination of both for the internet-mediated group . Characteristics of participants who were exposed to at least 75 % of the program material were explored . Descriptive analysis and logistical regression were used to examine differences between groups for program exposure . Results All groups showed decrease in program exposure over time . Differences were also observed ( χ2 = 10.37 , p < 0.05 ) , between intervention groups . The internet-mediated ( OR = 2.4 , 95 % CI 1.13–5.1 ) and internet-only ( OR = 2.96 , 95 % CI 1.38–6.3 ) groups were more likely to have been exposed to at least 75 % of the program compared to the face-to-face group . Participants with high physical activity self-efficacy were 1.82 ( 95 % CI 1.15–2.88 ) times more likely to have been exposed to 75 % of the program , and those allocated to the face-to-face group were less likely to have attended 75 % of the face-to-face sessions if they were classified as obese ( OR = 0.21 95 % CI 0.04–0.96 ) . Conclusion These results suggest that the internet groups were as effective as the face-to-face delivery mode in engaging participants in the program material . However , different delivery methods may be more useful to different sub- population s. It is important to explore which target groups that internet-based programs are best suited , in order to increase their impact The goal of evidence -based medicine is ultimately to improve patient outcomes and quality of care . Systematic review s of the available published evidence are required to identify interventions that lead to improvements in behavior , health , and well-being . Authoritative literature review s depend on the quality of published research and research reports . The Consoli date d St and ards for Reporting Trials ( CONSORT ) Statement ( www.consort-statement.org ) was developed to improve the design and reporting of interventions involving r and omized clinical trials ( RCTs ) in medical journals . We describe the 22 CONSORT guidelines and explain their application to behavioral medicine research and to evidence -based practice . Additional behavioral medicine-specific guidelines ( e.g. , treatment adherence ) are also presented . Use of these guidelines by clinicians , educators , policymakers , and research ers who design , report , and evaluate or review RCTs will strengthen the research itself and accelerate efforts to apply behavioral medicine research to improve the processes and outcomes of behavioral medicine practice BACKGROUND The literature suggests that people delay too long prior to attending emergency departments with acute coronary syndrome ( ACS ) symptoms . This delay is referred to as prehospital delay . Patient decision delay contributes most significantly to prehospital delay . OBJECTIVES Using a r and omized controlled trial , we tested an educational intervention to reduce patient prehospital delay in ACS and promote appropriate responses to symptoms . METHODS Eligible patients who were admitted across five emergency departments ( EDs ) in Dublin were recruited to the study ( n = 1944 ; control : 972 , intervention : 972 ) . RESULTS Median baseline prehospital delay times did not differ significantly between the groups at baseline ( Mann-Whitney U , p = 0.34 ) ( CONTROL : 4.28 h , 25(th ) percentile = 1.71 , 75(th ) percentile = 17.37 ; Intervention 3.96 h , 25(th ) percentile = 1.53 , 75(th ) percentile = 18.51 ) . Both groups received usual in-hospital care . In addition , patients r and omized to the intervention group received a 40-min individualized education session using motivational techniques . This was reinforced 1 month later by telephone . Of the 1944 , 314 ( 16.2 % ) were readmitted with ACS symptoms : 177 ( 18.2 % ) and 137 ( 14.1 % ) of the intervention and control groups , respectively . Prehospital delay times were again measured . Median delay time was significantly lower in the intervention compared to the control group ( 1.7 h vs. 7.1 h ; p ≤ 0.001 ) . Appropriately , those in the intervention group reported their symptoms more promptly to another person ( p = 0.01 ) and fewer consulted a general practitioner ( p = 0.02 ) . There was no significant difference in ambulance use ( p = 0.51 ) or nitrate use ( p = 0.06 ) between the groups . CONCLUSION It is possible to reduce prehospital delay time in ACS , but the need for renewed emphasis on ambulance use is important Loss to follow-up is often hard to avoid in r and omised trials . This article suggests a framework for intention to treat analysis that depends on making plausible assumptions about the missing data and including all participants in sensitivity We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a r and omised controlled trial . To develop the framework , we undertook a Delphi survey ; ran an open meeting at a trial methodology conference ; conducted a review of definitions outside the health research context ; consulted experts at an international consensus meeting ; and review ed 27 empirical pilot or feasibility studies . We initially adopted mutually exclusive definitions of pilot and feasibility studies . However , some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions . Their viewpoint was supported by definitions outside the health research context , the use of the terms ‘ pilot ’ and ‘ feasibility ’ in the literature , and participants at the international consensus meeting . In our framework , pilot studies are a subset of feasibility studies , rather than the two being mutually exclusive . A feasibility study asks whether something can be done , should we proceed with it , and if so , how . A pilot study asks the same questions but also has a specific design feature : in a pilot study a future study , or part of a future study , is conducted on a smaller scale . We suggest that to facilitate their identification , these studies should be clearly identified using the terms ‘ feasibility ’ or ‘ pilot ’ as appropriate . This should include feasibility studies that are largely qualitative ; we found these difficult to identify in electronic search es because research ers rarely used the term ‘ feasibility ’ in the title or abstract of such studies . Investigators should also report appropriate objectives and methods related to feasibility ; and give clear confirmation that their study is in preparation for a future r and omised controlled trial design ed to assess the effect of an intervention PURPOSE To compare delay and circumstances of decisions to seek care in patients with acute myocardial infa rct ion ( AMI ) in the United States ( US ) , Engl and , Australia , South Korea , and Japan . DESIGN Comparative prospect i ve design . METHODS Patients diagnosed with AMI ( N = 913 ) were interviewed within 72 hours of hospital admission for confirmed AMI using the Response to Symptoms Question naire . Delay times were calculated from review of emergency room records and patients ' interviews . Analysis of variance was used to test differences in delay time among countries . FINDINGS Median delay ranged from 2.5 hours in Engl and to 6.4 hours in Australia , with the three Pacific Rim countries reporting median delay times > 4 hours . The majority of patients experienced initial symptoms at home ( range : 56 % in Japan to 73 % in the US ) with the most common witness being a family member ( 32 % in South Korea to 48 % in Engl and ) . Ambulance use was widely divergent with the highest use in Engl and ( 85 % ) and the lowest use in the US ( 42 % ) . CONCLUSIONS In all countries , median delay was too long to obtain maximum benefit from AMI therapies , particularly thrombolysis . Education and counseling of patients and families to reduce prehospital delay in AMI episodes might be more effective if the various factors influencing patients ' first responses to symptoms are considered , as well as differences in health care systems A consistent finding in health services research is the report of uneven uptake of research findings . Implementation trials have a variable record of success in effectively influencing clinicians ' behaviour . A more systematic approach may be to conduct Intervention Modelling Experiments before service-level trials , examining intervention effects on ' interim endpoints ' representing clinical behaviour , derived from empirically supported psychological theories . The objectives were to : ( 1 ) Design Intervention Modelling Experiments by backward engineering a ' real-world ' r and omised controlled trial ( NEXUS ) ; ( 2 ) examine the applicability of psychological theories to clinical decision-making ; ( 3 ) explore whether psychological theories can illuminate how interventions achieve their effects . A 2 x 2 factorial r and omised controlled trial was design ed with pre- and post-intervention data collection by postal question naire surveys . The first survey was used to generate feedback data and the interventions were delivered in the second survey . General medical practitioners ( GPs ) in Engl and and Scotl and participated . First survey respondents were r and omised twice to receive or not audit and feedback and educational reminder messages . The main outcome measures included behavioural intention ( general plan to refer for lumbar X-rays ) and simulated behaviour ( specific , scenario-based , decisions to refer for lumbar X-ray ) . Predictors were attitude , subjective norm , perceived behavioural control ( theory of planned behaviour ) , self-efficacy ( social cognitive theory ) and decision difficulty . Both interventions significantly influenced simulated behaviour , but neither influenced behavioural intention . There were no interaction effects . All theoretically derived cognitions significantly predicted simulated behaviour . Only subjective norm was not predictive of behavioural intention . The effect of audit and feedback on simulated behaviour was mediated through perceived behavioural control . The results of this study suggest that Intervention Modelling Experiments , using psychological models to help isolate mediators of clinical decision-making , may be a means of developing more potent interventions , and selecting implementation interventions with a greater likelihood of success in a service-level r and omised controlled trial CONTEXT Delayed access to medical care in patients with acute myocardial infa rct ion ( AMI ) is common and increases myocardial damage and mortality . OBJECTIVE To evaluate a community intervention to reduce patient delay from symptom onset to hospital presentation and increase emergency medical service ( EMS ) use . DESIGN AND SETTING The Rapid Early Action for Coronary Treatment Trial , a r and omized trial conducted from 1995 to 1997 in 20 US cities ( 10 matched pairs ; population range , 55,777 - 238,912 ) in 10 states . PARTICIPANTS A total of 59,944 adults aged 30 years or older presenting to hospital emergency departments ( EDs ) with chest pain , of whom 20,364 met the primary population criteria of suspected acute coronary heart disease on admission and were discharged with a coronary heart disease-related diagnosis . INTERVENTION One city in each pair was r and omly assigned to an 18-month intervention that targeted mass media , community organizations , and professional , public , and patient education to increase appropriate patient actions for AMI symptoms ( primary population , n=10,563 ) . The other city in each pair was r and omly assigned to reference status ( primary population , n=9801 ) . MAIN OUTCOME MEASURES Time from symptom onset to ED arrival and EMS use , compared between intervention and reference city pairs . RESULTS General population surveys provided evidence of increased public awareness and knowledge of program messages . Patient delay from symptom onset to hospital arrival at baseline ( median , 140 minutes ) was identical in the intervention and reference communities . Delay time decreased in intervention communities by -4.7 % per year ( 95 % confidence interval [ CI ] , -8.6 % to -0.6 % ) , but the change did not differ significantly from that observed in reference communities ( -6 . 8 % per year ; 95 % CI , -14.5 % to 1.6 % ; P=.54 ) . EMS use by the primary study population increased significantly in intervention communities compared with reference communities , with a net effect of 20 % ( 95 % CI , 7%-34 % ; P<.005 ) . Total numbers of ED presentations for chest pain and patients with chest pain discharged from the ED , as well as EMS use among patients with chest pain released from the ED , did not change significantly . CONCLUSIONS In this study , despite an 18-month intervention , time from symptom onset to hospital arrival for patients with chest pain did not change differentially between groups , although increased appropriate EMS use occurred in intervention communities . New strategies are needed if delay time from symptom onset to hospital presentation is to be decreased further in patients with suspected AMI . JAMA . 2000;284:60 - Thrombolytic therapy for acute myocardial infa rct ion ( AMI ) is now routinely given in the emergency department and is being considered for pre-hospital care . Its effectiveness is dependent on how early it can be given after the onset of AMI . Maximal benefit , however , is not realized in many patients due to delay in seeking care . The effect of a public media education campaign ( message ) to shorten patient delay and increase use of emergency medical services ( EMS ) was evaluated prospect ively in King County , Washington . We interviewed 401 patients admitted with possible AMI in the premessage period ( 4.5 months ) and 489 in the postmessage period ( 4.5 months ) . The two groups were comparable in all factors except for discharge diagnosis of AMI ( premessage , 34 % ; postmessage , 25 % ; P less than .01 ) and history of myocardial infa rct ion or angina ( premessage , 52 % ; postmessage , 43 % ; P less than .01 ) . The proportion of patients who heard new information on AMI increased significantly in the postmessage period ( premessage , 53 % ; postmessage , 74 % ; P less than .0001 ) . The campaign , however , did not significantly shorten patient delay in seeking care ( median delay : premessage , 2.6 hours ; postmessage , 2.3 hours ) or alter the distribution of patients in the less-than-two-hour , two-to-four-hour , and more-than-four-hour intervals . The rate of EMS use also was not significantly changed ( premessage , 42 % ; postmessage , 44 % ) . We conclude that a short- duration education campaign may increase AMI knowledge but does not seem to significantly alter patient behavior BACKGROUND Most individuals with lung cancer have symptoms for several months before presenting to their GP . Earlier consulting may improve survival . AIM To evaluate whether a theory-based primary care intervention increased timely consulting of individuals with symptoms of lung cancer . DESIGN AND SETTING Open r and omised controlled trial comparing intervention with usual care in two general practice s in north-east Scotl and . METHOD Smokers and ex-smokers aged ≥55 years were r and omised to receive a behavioural intervention or usual care . The intervention comprised a single nurse consultation at participants ' general practice and a self-help manual . The main outcomes were consultations within target times for individuals with new chest symptoms ( ≤3 days haemoptysis , ≤3 weeks other symptoms ) in the year after the intervention commenced , and intentions about consulting with chest symptoms at 1 and 6 months . RESULTS Two hundred and twelve participants were r and omised and 206 completed the trial . The consultation rate for new chest symptoms in the intervention group was 1.19 ( 95 % confidence interval [ CI ] = 0.92 to 1.53 ; P = 0.18 ) times higher than in the usual-care group and the proportion of consultations within the target time was 1.11 ( 95 % CI = 0.41 to 3.03 ; P = 0.83 ) times higher . One month after the intervention commenced , the intervention group reported intending to consult with chest symptoms 31 days ( 95 % CI = 7 to 54 ; P = 0.012 ) earlier than the usual care group , and at 6 months this was 25 days ( 95 % CI = 1.5 to 48 ; P = 0.037 ) earlier . CONCLUSION Behavioural intervention in primary care shortened the time individuals at high risk of lung disease intended to take before consulting with new chest symptoms ( the secondary outcome of the study ) , but increases in consultation rates and the proportions of consultations within target times were not statistically significant The time that elapses from the onset of symptoms of acute myocardial infa rct ion ( AMI ) to treatment has a significant effect on mortality and morbidity . This study reports the effectiveness of an education and counselling intervention on knowledge , attitudes and beliefs about AMI symptoms and the appropriate response to symptoms . The intervention was tested in a r and omised controlled trial of 200 people with a history of coronary heart disease ( CHD ) . The groups were equivalent at baseline on study outcomes , clinical history and sociodemographic characteristics with the exception of more women in the intervention group ( 38 % vs. 24 % ) . The results of repeated measures ANOVA showed that the intervention result ed in improved knowledge of CHD , AMI symptoms and the appropriate response to symptoms that was sustained to 12 months ( p = 0.02 ) . There were no differences between groups ' attitudes and beliefs over time . It is concluded that a short individual teaching and counselling intervention result ed in improved knowledge of CHD , AMI symptoms and the appropriate response to symptoms in people at risk of AMI sustained to 12 months Introduction Delay to presentation with symptoms of acute coronary syndrome ( ACS ) is common meaning many fail to achieve optimal benefit from treatments . Interventions have had variable success in reducing delay . Evidence suggests inclusion of behaviour change techniques ( BCTs ) may improve effectiveness of interventions but this has not yet been systematic ally evaluated . Data from other time-critical conditions may be relevant . Methods and analysis A systematic review will be undertaken to identify which BCTs are associated with effective interventions to reduce patient delay ( or prompt rapid help-seeking ) among people with time-critical conditions ( eg , chest pain , ACS , lumps , stroke , cancer and meningitis ) . A systematic search of a wide range of data bases ( including Cochrane Library , MEDLINE , EMBASE , CINAHL , PsycInfo ) and grey literature will be undertaken to identify all relevant intervention studies ( r and omised controlled trials , controlled clinical trials and cohort studies ) . Two independent review ers will screen abstract s to identify relevant studies , apply inclusion criteria to full papers , assess method ological quality and extract data . Primary outcome measure Change in patient decision time BCTs reported in each of the included studies will be categorised and presented according to the latest reliable taxonomy . Results of included studies will be synthesis ed , exploring relationships between inclusion of each BCT and effectiveness of the overall intervention . Where possible , means and SDs for differences in delay time will be calculated and combined within meta-analyses to derive a st and ardised mean difference and 95 % CI . Analysis of ( 1 ) all time-critical and ( 2 ) ACS-only interventions will be undertaken . Ethics and dissemination No ethical issues are anticipated . Results will be su bmi tted for publication in a relevant peer- review ed journal OBJECTIVES To evaluate the robustness of the intervention modeling experiment ( IME ) methodology as a way of developing and testing behavioral change interventions before a full-scale trial by replicating an earlier paper-based IME . STUDY DESIGN AND SETTING Web-based question naire and clinical scenario study . General practitioners across Scotl and were invited to complete the question naire and scenarios , which were then used to identify predictors of antibiotic-prescribing behavior . These predictors were compared with the predictors identified in an earlier paper-based IME and used to develop a new intervention . RESULTS Two hundred seventy general practitioners completed the question naires and scenarios . The constructs that predicted simulated behavior and intention were attitude , perceived behavioral control , risk perception/anticipated consequences , and self-efficacy , which match the targets identified in the earlier paper-based IME . The choice of persuasive communication as an intervention in the earlier IME was also confirmed . Additionally , a new intervention , an action plan , was developed . CONCLUSION A web-based IME replicated the findings of an earlier paper-based IME , which provides confidence in the IME methodology . The interventions will now be evaluated in the next stage of the IME , a web-based r and omized controlled trial The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
10,332 | 22,030,441 | Our review suggests that silver-containing dressings and topical silver were either no better or worse than control dressings in preventing wound infection and promoting healing of burn wounds | Silver preparations are commonly used for burns , but evidence of their effectiveness remains poorly defined .
The aim of the study was to evaluate the effectiveness of silver-containing dressings and topical silver for preventing infection and promoting healing in burns wounds through a meta- analysis of the available evidence . | Local treatment of burn injuries with conventional anti-infective preparations does not provide the moist environment that promotes fast wound healing . In a r and omized controlled trial the effects of liposome polyvinyl-pyrrolidone-iodine ( PVP-I ) hydrogel , a novel formulation of PVP-I in a liposome hydrogel with high water-binding capacity , were investigated in 43 patients with partial-thickness burn wounds in an intraindividual comparison with a conventional silver-sulfadiazine cream . Treatment with liposome PVP-I hydrogel result ed in significantly faster complete healing of the burn wounds compared with silver-sulfadiazine cream ( 9.9 ± 4.5 days versus 11.3 ± 4.9 ; P < 0.015 ) . The cosmetic result ( smoothness , elasticity , appearance ) was rated as excellent for 37.0 % of study wounds with liposome PVP-I hydrogel compared with 13.0 % of wounds treated with silver-sulfadiazine cream . Local tolerability was good ; h and ling and change of dressing were rated as easy . Local treatment with liposome PVP-I hydrogel thus provides fast wound healing with a favorable cosmetic result St and ard treatment for extensive partial-thickness burns in the United States and in much of the world involves the application of topical antimicrobial agents and repetitive wound débridements and dressing changes . We evaluated a new biologic wound covering , TransCyte ( Advanced Tissue Sciences , La Jolla , Calif , formerly marketed as Dermagraft-Transitional Covering ) , for the treatment of partial-thickness burns . This material is composed of human newborn fibroblasts which are then cultured on the nylon mesh of Biobrane ( Dow B. Hickam , Inc , Sugarl and , Tex ) ; the thin silicone membrane bonded to the mesh provides a moisture vapor barrier for the wound . A prospect i ve , r and omized , comparison study of silver sulfadiazine and TransCyte was performed with the use of paired wound sites on 14 patients . Wounds treated with TransCyte healed more quickly ( mean 11.14 days to 90 % epithelialization vs 18.14 days , P = .002 ) . A noncomparison evaluation was then done for an additional 18 patients , and it confirmed excellent wound healing and an absence of infections . There were no infections in the 32 wound sites treated with TransCyte . In the first study group , late wound evaluations ( 3 , 6 , and 12 months postburn ) were performed with use of the Vancouver Scar Scale . The results indicated that wound sites treated with TransCyte healed with less hypertrophic scarring than sites treated with silver sulfadiazine ( P < .001 at 3 and 6 months , P = .006 at 12 months ) Histological and clinical studies of wound healing have been made on comparable fresh partial thickness burns with honey dressing or silver sulfadiazine ( SSD ) in two groups of 25 r and omly allocated patients . Of the wounds treated with honey 84 per cent showed satisfactory epithelialization by the 7th day , and in 100 per cent of the patients by the 21st day . In wounds treated with silver sulfadiazine , epithelialization occurred by the 7th day in 72 per cent of the patients and in 84 per cent of patients by 21 days . Histological evidence of reparative activity was seen in 80 per cent of wounds treated with the honey dressing by the 7th day with minimal inflammation . Fifty two per cent of the silver sulfadiazine treated wounds showed reparative activity with inflammatory changes by the 7th day . Reparative activity reached 100 per cent by 21 days with the honey dressing and 84 per cent with SSD . Thus in honey dressed wounds , early subsidence of acute inflammatory changes , better control of infection and quicker wound healing was observed while in the SSD treated wounds sustained inflammatory reaction was noted even on epithelialization To compare the effect of honey dressing and silver-sulfadiazene ( SSD ) dressing on wound healing in burn patients . Patients ( n=78 ) of both sexes , with age group between 10 and 50 years and with first and second degree of burn of less than 50 % of TBSA ( Total body surface area ) were included in the study , over a period of 2 years ( 2006 - 08 ) . After stabilization , patients were r and omly attributed into two groups : ‘ honey group ’ and ‘ SSD group ’ . Time elapsed since burn was recorded . After washing with normal saline , undiluted pure honey was applied over the wounds of patients in the honey group ( n=37 ) and SSD cream over the wounds of patients in SSD group ( n=41 ) , everyday . Wound was dressed with sterile gauze , cotton pads and b and aged . Status of the wound was assessed every third and seventh day and on the day of completion of study . Patients were followed up every fortnight till epithelialization . The bacteriological examination of the wound was done every seventh day . The mean age for case ( honey group ) and control ( SSD group ) was 34.5 years and 28.5 years , respectively . Wound swab culture was positive in 29 out of 36 patients who came within 8 hours of burn and in all patients who came after 24 hours . The average duration of healing in patients treated with honey and SSD dressing at any time of admission was 18.16 and 32.68 days , respectively . Wound of all those patients ( 100 % ) who reported within 1 hour became sterile with honey dressing in less than 7 days while none with SSD . All of the wounds became sterile in less than 21 days with honey , while tthis was so in only 36.5 % with SSD treated wounds . The honey group included 33 patients reported within 24 hour of injury , and 26 out of them had complete outcome at 2 months of follow-up , while numbers for the SSD group were 32 and 12 . Complete outcome for any admission point of time after 2 months was noted in 81 % and 37 % of patients in the honey group and the SSD group . Honey dressing improves wound healing , makes the wound sterile in lesser time , has a better outcome in terms of prevention of hypertrophic scarring and post-burn contractures , and decreases the need of debridement irrespective of time of admission , when compared to SSD dressing Background R and omized trials are essential in assessing the effects of healthcare interventions and are a key component in systematic review s of effectiveness . Search ing for reports of r and omized trials in data bases is problematic due to the absence of appropriate indexing terms until the 1990s and inconsistent application of these indexing terms thereafter . Objectives The objectives of this study are to devise a search strategy for identifying reports of r and omized trials in EMBASE which are not already indexed as trials in MEDLINE and to make these reports easily accessible by including them in the Cochrane Central Register of Controlled Trials ( CENTRAL ) in The Cochrane Library , with the permission of Elsevier , the publishers of EMBASE . Methods A highly sensitive search strategy was design ed for EMBASE based on free-text and thesaurus terms which occurred frequently in the titles , abstract s , EMTREE terms ( or some combination of these ) of reports of trials indexed in EMBASE . This search strategy was run against EMBASE from 1980 to 2005 ( 1974 to 2005 for four of the terms ) and records retrieved by the search , which were not already indexed as r and omized trials in MEDLINE , were downloaded from EMBASE , printed and read . An analysis of the language of publication was conducted for the reports of trials published in 2005 ( the most recent year completed at the time of this study ) . Results Twenty-two search terms were used ( including nine which were later rejected due to poor cumulative precision ) . More than a third of a million records were downloaded and scanned and approximately 80,000 reports of trials were identified which were not already indexed as r and omized trials in MEDLINE . These are now easily identifiable in CENTRAL , in The Cochrane Library . Cumulative sensitivity ranged from 0.1 % to 60 % and cumulative precision ranged from 8 % to 61 % . The truncated term ' r and om$ ' identified 60 % of the total number of reports of trials but only 35 % of the more than 130,000 records retrieved by this term were reports of trials . The language analysis for the sample year 2005 indicated that of the 18,427 reports indexed as r and omized trials in MEDLINE , 959 ( 5 % ) were in language s other than English . The EMBASE search identified an additional 658 reports in language s other than English , of which the highest number were in Chinese ( 320 ) . Conclusion The results of the search to date have greatly increased access to reports of trials in EMBASE , especially in some language s other than English . The search strategy used was subjectively derived from a small ' gold st and ard ' set of test records and was not vali date d in an independent test set . We intend to design an objective ly-derived vali date d search strategy using logistic regression based on the frequency of occurrence of terms in the approximately 80,000 reports of r and omized trials identified compared with the frequency of these terms across the entire EMBASE data base Acticoat , a new silver-coated dressing , produces a moist healing environment along with the sustained release of ionic silver for improved microbial control . These properties suggest that Acticoat might be a useful donor site dressing . However , there are no human studies which assess Acticoat for this use . The purpose of this study was to compare the healing of human skin graft donor sites dressed with Acticoat , to the healing of those dressed with Allevyn , an occlusive moist-healing environment material , which is our st and ard donor site dressing . In burn patients who had undergone burn excision and grafting , identical side-by-side split thickness donor site wound pairs were dressed with Allevyn and Acticoat . Re-epithelialization was directly assessed daily by a single observer from post-operative day 6 onward , and by four independent observers who rated the extent of re-epithelialization by viewing st and ardized digital images of the wounds that had been obtained on post-operative days 6 , 8 , 10 , and 12 . Donor sites were swabbed for bacterial culture on days 3 , 6 , and 9 . Subsequently , each study donor site scar was rated by a blinded observer using the Vancouver Scar Scale at 1 , 2 , and 3 months . Sixteen paired sites in 15 patients ( 3 female , 12 male ) were studied . Donor sites dressed with Allevyn were > 90 % re-epithelialized at a mean of 9.1+/-1.6 days while donor sites dressed with Acticoat required a mean of 14.5+/-6.7 days to achieve > 90 % re-epithelialization ( P=0.004 ) . The Allevyn sites had significantly greater estimated re-epithelialization at days 6 , 8 , 10 and 12 than the Acticoat sites based on the observations of the digital images . There were no significant differences in the incidence of positive bacterial cultures with either dressing at days 3 , 6 , and 9 . Donor sites dressed with Acticoat had significantly worse scars at 1 and 2 months but this difference resolved by 3 months . Our findings do not support the use of Acticoat as a skin graft donor site dressing OBJECTIVE To explore the influence of silver nanoparticle dressing on prevention of infection and healing of the second degree burn wound . METHODS One hundred and ninety-one burn patients with second degree including superficial and deep burn wound were r and omly divided into three groups . Group A including 65 cases was treated by silver nanoparticle dressing on wounds , and group B ( 63 cases ) and group C ( 63 cases ) were treated by 1 % silver sulfadiazine cream and vaseline gauze on their wounds , respectively . Dressing was changed daily , and wound swab bacterial cultures were performed before and after dressing change , and also wound healing times were recorded in each patient . RESULTS Group A and B were similar in their bacterium colonizations on wound after treatment with the silver nanoparticle dressing and 1 % silver sulfadiazine cream , and they had a similar effect on reducing bacterium colonization on wound after treatment , while in vaseline gauze group bacterium colonization on wound increased after treatment . In group A the wound healing time of superficial second degree was significantly shorter than those in group B and group C ( P < 0.01 ) . In deep second degree wounds the healing time in group A was much shorter than that in group C ( P < 0.01 ) , but had no significant difference when compared with group B ( P > 0.05 ) . CONCLUSION Silver nanoparticle dressing can be used on second degree burn wound and can decrease the risk of wound infection and accelerate wound healing Mepitel is a new grid like silicone coated nylon dressing containing no additional biological compounds . We describe a prospect i ve r and omized pilot study comparing Mepitel to the st and ard silver sulfadiazine cream ( Flamazine ) dressing for the topical treatment of paediatric burns . Seventy-six children presenting within 24 h of injury with a non previously treated burn were r and omly assigned to Mepitel treatment ( group M ) or Flamazine treatment ( group F ) . Age , sex , surface area of burn and causal agent were noted at admission . The depth of the burn , cumulative number of dressings , presence or absence of a complete epithelial cover , infection , bleeding and allergy were noted at each dressing change . There were 41 children in group M and 35 children in group F. Five children were subsequently withdrawn from each group because they required skin grafting . Analysis of the above mentioned criteria showed no statistical difference between the two groups except for the healing time ( group M : 7.58+/-3.12 , group F : 11.26+/-6.02 , p < 0.01 ) and the number of dressings ( group M : 3.64+/-1.5 , group F : 5.13+/-2.9 , p < 0.05 ) . Mepitel has proved to be an easy-to-remove dressing , adhering only to intact skin . The faster healing time found in the Mepitel group may be related to a direct effect of silicone on epithelial growth or to a decrease in surface-cell damage compared to the silver sulfadiazine group . This attractive product will be further assessed on a larger scale trial to confirm our observations Since its introduction into clinical practice in 1967 by Charles Fox Jr. , silver sulfadiazine has been the gold st and ard for topical burn therapy . The addition to it of hyaluronic acid , which forms a substantial part of the human tissue intercellular matrix , is aim ed at overcoming one of its very few disadvantages , i.e. prolongation of the wound re-epithelialization process . Since both hyaluronic acid and silver sulfadiazine have been used in therapy for decades and their efficacy is well documented , a topical treatment combining these two agents was formulated . The aim of the study was to investigate the efficacy and tolerability of a cream containing a hyaluronic acid/silver sulfadiazine fixed combination , compared with silver sulfadiazine cream alone , for the treatment of superficial and deep second-degree burns in a prospect i ve , double-blind , controlled clinical study . The findings of the study confirmed that the association of the two compounds in a new topical treatment significantly reduced the healing time and significantly accelerated the reduction of local edema occurring shortly after injury . Furthermore , this new hyaluronic acid and silver sulfadiazine formulation has proven to have favorable antibacterial , anti-edematous and local analgesic effects , together with a clear stimulatory activity on the re-epithelialization process . This product may , therefore , significantly enrich the assortment of topical medications available for the treatment of burns and skin defects of other origin A r and omized , prospect i ve study comparing the use of Biobrane ( group 1 ) with the use of 1 % silver sulfadiazine ( group 2 ) in treating 56 partial-thickness burn wounds was carried out in 52 out patients with burns that comprised less than 10 % of their total body surface area . The two groups were similar in age , gender , race , and extent of burn . Wounds of patients in group 1 ( 30 ) were compared with those of group 2 ( 26 ) for healing time , pain , compliance with scheduled visits , and costs . Infected and skin-grafted wounds were excluded from healing time analysis . Infection rates of the two groups were similar ( three of 30 vs two of 26 ) . One patient in each group underwent skin grafting . Healing times of group 1 wounds were significantly less than those of group 2 ( 10.6 + /- 0.8 vs 15.0 + /- 1.2 days , P less than .01 ) . Using a pain scale of 1 to 5 , Biobrane-treated patients averaged lower pain scores at 24 hours after the burn ( 1.6 + /- 0.8 vs 3.6 + /- 1.3 P less than .001 ) and used less pain medication . Compliance with scheduled outpatient visits was also improved in the Biobrane-treated group ( 88.6 % vs 63.2 % attendance , P less than .001 ) . Idealized total treatment costs averaged $ 434 for patients in group 1 compared with $ 504 for patients in group 2 . We conclude that when used on properly selected wounds , Biobrane therapy can significantly decrease pain and total healing time without increasing the cost of outpatient burn care . Improved patient compliance may be an added benefit The purpose of this r and omised comparative study was to evaluate the use of silver sulphadiazine ( SSD ) 1 % cream ( Group A ) with the use of Procutase ( Group B ) in treating burns with a TBSA < 10 % and a depth not greater than 2nd degree burns and thus suitable for outpatient management . The two groups were similar in age , gender , race , and extent of burn . Procutase is an ionic hydrogel composed of natural hydrophilic polymers in an active ionic solution with an inhibitor of matrix metalloproteinases MMP-1 , -3 and -9 ( collagenase/gelatinase ) . Subjects were seen in follow-up biweekly , and wounds of patients in SSD group were compared with those of Procutase group for healing time , pain score at dressing change , compliance with therapy and complication rate . The result of this study showed that Procutase treated patients had statistically significantly less pain and shorter wound healing time . Procutase can be used successfully in patients with burns that do not require hospital admission The purpose of this prospect i ve r and omized study was to evaluate the use of an occlusive hydrocolloid dressing ( Duoderm hydroactive , Squibb ) and silver sulfadiazine ( Silvadene , Marion ) cream in the outpatient management of second-degree burns . The inclusion criteria consisted of burns less than 15 % total body surface area that were evaluated within 24 hours of injury and did not require hospital admission . Fifty patients were r and omly assigned after having been screened through a list of seven exclusion criteria . On initial evaluation the burns were photographed and screened for causative agent , location , size , depth , tetanus status , and presence of associated burns and injuries . Patients were seen in followup at least biweekly and evaluated for wound bed healing , wound margin healing , pain , number of dressing changes between visits , and ease of dressing application and removal . On final evaluation the burns were photographed and inspected for appearance of the healed burn , repigmentation , wound contraction , approximate time for dressing change , patient compliance , limitation of activity , overall impression of the treatment , and number of days for complete healing . Results were compared using a two-tailed t-test with p less than 0.01 . Both groups were statistically similar in age , sex , and size . Duoderm-treated burns had statistically significantly better wound healing , repigmentation , less pain , fewer dressing changes , less time for dressing changes , and less cost . Duoderm-treated patients had statistically significantly less limitation of activity , better patient compliance , greater patient comfort , better overall acceptance , and felt the treatment was more aesthetically pleasing . The results reveal that the Duoderm Hydroactive dressings are superior to Silvadene cream in the outpatient management of second-degree burns BACKGROUND Fungal infections of burn wounds have become an important cause of burn-associated morbidity and mortality . The nature of fungal infections dictates aggressive treatment to minimize the morbidity associated with these infections . Persons with large total body surface area burns are particularly susceptible to fungal infections and are treated in such a manner as to minimize their risk of infection . METHODS This study examined the in vitro fungicidal efficacy of a variety of different topical agents . By placing fungal inocula in contact with mafenide acetate , silver nitrate , silver sulfadiazine , and a nanocrystalline silver-coated dressing , we determined the kill kinetics of these topical agents against a spectrum of common burn wound fungal pathogens . RESULTS The topical antimicrobials that were tested demonstrated varying degrees of efficacy against these pathogens . CONCLUSION The nanocrystalline silver-based dressing provided the fastest and broadest-spectrum fungicidal activity and may make it a good c and i date for use to minimize the potential of fungal infection , thereby reducing complications that delay wound healing A comparison of low-gel hydrocolloids with and without medication and chlorhexidine tulle gras , as bacteriological barriers in minor We performed a r and omized clinical trial in which children with partial-thickness scald burns of less than 15 % total body surface area were assigned treatment with either Mepitel ( Mölnlycke Health Care ) or silver sulfadiazine . Data were collected on time to wound healing , pain at dressing change , infection , and re source use . Student 's t and chi-square tests were used to determine differences in the two groups . Healing times were compared using Kaplan-Meier survival curves . Wounds of children treated with Mepitel healed significantly faster than did controls ' ( p < 0.001 ) , exhibited less eschar formation ( p < 0.05 ) , and experienced less pain at dressing change ( p < 0.05 ) . They also had significantly lower mean daily hospital charges ( $ 1937 vs $ 2316 ; p = 0.025 ) ; as well as significantly lower charges for dressing changes and narcotics . There was no significant difference in wound infection . We believe the use of Mepitel represents a significant advance in the treatment of partial-thickness scald wounds in children OBJECTIVE A prospect i ve , r and omized , controlled single center study was design ed to evaluate clinical efficacy of a polyhexanide containing bio-cellulose dressing ( group B ) compared to a silver-sulfadiazine cream ( group A ) in sixty partial-thickness burn patients . PATIENTS AND METHODS Local ethics committee approval was obtained and patients consented . Parameters were : pain reduction ( VAS ) , healing time and wound bed condition , comparing day 0 ( start ) versus day 14 ( end ) , as well as , ease of dressing use and treatment costs . RESULTS All completed the study ( n=30/n=30 ) and were included in the ITT analysis , with a total of 72 burns ( group A : n=38 , group B : n=34 ) . We noted no differences in healing time . Pain reduction was significantly faster and better in group B ( p<0.01 ) . There were fewer dressing changes in group B , compared to group A. Ease of use for the bio-cellulose dressing was rated better compared to group A. In group B , € 95.20 was saved for a 10 day treatment period , compared to group A. CONCLUSION Group B demonstrated a better and faster pain reduction in the treated partial-thickness burns , compared to group A. The results indicate the polyhexanide containing bio-cellulose dressing to be a safe and cost effective treatment for partial-thickness burns |
10,333 | 32,289,734 | The use of crossover design s and too high illumination as placebo lights might have nullified positive effects of BLT . | Dementia is a devastating disease with a global impact , and there is an urgent need for effective interventions to alleviate the accompanying disturbances in behavior , mood , sleep , and circadian rhythms .
Bright light treatment ( BLT ) is a promising non-pharmacological intervention ; however , studies have yielded conflicting results .
This systematic review provides a comprehensive overview of the effect of BLT in dementia , with a specific focus on how study characteristics might have affected the available results . | The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation , is unknown . The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help eluci date the ocular photoreceptor system for regulating the human pineal gl and . Subjects ( 37 females , 35 males , mean age of 24.5 ± 0.3 years ) were healthy and had normal color vision . Full-field , monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects ' pupils were dilated . Blood sample s collected before and after light exposures were quantified for melatonin . Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure . Nighttime melatonin suppression tests ( n = 627 ) were completed with wavelengths from 420 to 600 nm . The data were fit to eight univariant , sigmoidal fluence – response curves ( R2 = 0.81–0.95 ) . The action spectrum constructed from these data fit an opsin template ( R2 = 0.91 ) , which identifies 446–477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion . The results suggest that , in humans , a single photopigment may be primarily responsible for melatonin suppression , and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision . The data also suggest that this new photopigment is retinaldehyde based . These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception STUDY OBJECTIVES Sleep pattern and circadian rhythms are regulated via the retinohypothalamic tract in response to stimulation of a subset of retinal ganglion cells , predominantly by blue light ( 450 - 490 nm ) . With age , the transmission of blue light to the retina is reduced because of the aging process of the human lens , and this may impair the photoentrainment of circadian rhythm leading to sleep disorders . The aim of the study was to examine the association between lens aging and sleep disorders . DESIGN Cross-sectional population based study . SETTING The study was performed at the Research Center for Prevention and Health , Glostrup Hospital , Denmark and at the Department of Ophthalmology , Herlev Hospital , Denmark . PARTICIPANTS An age- and sex-stratified sample of 970 persons aged 30 to 60 years of age drawn from a sample r and omly selected from the background population . INTERVENTIONS Not applicable . MEASUREMENTS AND RESULTS Sleep disturbances were evaluated by a combination of question naire and the use of prescription sleeping medication . Lens aging ( transmission and yellowing ) was measured objective ly by lens autofluorometry . The risk of sleep disturbances was significantly increased when the transmission of blue light to the retina was low , even after correction for the effect of age and other confounding factors such as smoking habits , diabetes mellitus , gender , and the risk of ischemic heart disease ( P < 0.0001 ) . CONCLUSIONS Filtration of blue light by the aging lens was significantly associated with an increased risk of sleep disturbances . We propose that this is a result of disturbance of photoentrainment of circadian rhythms ABSTRACT This secondary analysis examined whether the benefits of bright light therapy on depression are greater in persons with mild/moderate or severe dementia . Exploratory analyses were also conducted to determine if bright light treatment targets different depressive symptom clusters based on dementia severity . Analyses using total scores from the instruments , Depressive Symptom Assessment for Older Adults and the Cornell Scale for Depression in Dementia , showed that bright light exposure is an equally effective intervention for depression in persons with both mild/moderate and severe dementia . Analyses of individual depressive subscales revealed that for disagreeable behavior and sleep impairment , bright light therapy appears to have greater benefits in persons with severe dementia than for those with mild/moderate dementia . Overall , this investigation supports the use of bright light therapy to treat depression regardless of dementia severity This study examined the effects of bright light exposure on three measures of depression and four measures of agitation in persons with dementia residing in long-term care . Using a r and omized controlled design , participants were r and omly assigned to receive either bright light ( n = 30 ) or low intensity light ( n = 30 ) for eight weeks . Bright light exposure was associated with significant improvement in depression and agitation , while participants receiving low intensity light displayed higher levels of depression and agitation or no significant change . Findings support the use of bright light exposure to reduce depression and agitation in this population Ten elderly subjects with severe dementia were given bright light ( 5000 - 8000 lux ) for 45 min each morning for 4 weeks . Two rating scales of behavioral symptoms in dementia were used as outcome measures : Cohen-Mansfield Agitation Inventory ( CMAI ) and Behavior Pathology In Alzheimer 's Disease Rating Scale ( BEHAVE-AD ) , a scale for sleep-wake disturbances , and actigraphy to monitor activity rhythm . Behavioral symptoms improved with treatment . No changes in sleep-wake measures were found . There was an advance of the activity rhythm acrophase during treatment . These results suggest that short-time bright light improves behavioral symptoms and aspects of activity rhythm disturbances even in severely demented subjects Two hundred ten community-dwelling patients with Alzheimer 's disease were examined prospect ively by psychiatrists as part of a longitudinal study . Twenty-five of these patients who were institutionalized during the next 3 years were then matched to 25 patients who were not institutionalized , and the groups were compared . The patients who had been institutionalized had higher scores on st and ardized psychiatric rating scales but not on formal neuropsychological tests of cognition . These results suggest that potentially treatable ( noncognitive ) behavioral and psychiatric symptoms are risk factors for institutionalization , and that treating these symptoms might delay or prevent institutionalization of some patients We investigated whether low intensity dawn-dusk simulation ( DDS ) , a ' naturalistic ' form of light therapy design ed to embed sleep in its accustomed phase , could improve the disturbed circadian rest-activity cycle , nocturnal sleep and and /or cognitive functions in dementia . A protocol of 3 weeks each of baseline , treatment and follow-up was completed by 13 patients ( 85yr old+/-5yr , MMSE 14+/-5 ; n=9 DDS versus n=4 ' placebo ' dim red light ) who wore an activity/lux monitor throughout . There were no significant changes in clinical or cognitive status , nor modification of circadian stability or amplitude characteristics of the rest-activity cycle . However , two aspects of sleep responded to DDS but not to dim red light . The main sleep episode was 1:14h earlier during treatment ( p=0.03 ) compared with before and after DDS . With respect to actimetry-determined sleep variables , the DDS group tended to have shortened ' sleep latency ' , longer ' sleep duration ' , more nocturnal immobility and less nocturnal activity than the dim red group ( p<0.1 ) . In parallel , nighttime light exposure tended to be reduced ( p=0.07 ) . These promising findings -after only 3 weeks of light treatment in elderly patients with advanced dementia-suggest that the circadian timing system remains functionally responsive even to low intensity DDS light . Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia , and DDS light therapy may provide one of the appropriate means to do so Background The ' Hawthorne Effect ' may be an important factor affecting the generalisability of clinical research to routine practice , but has been little studied . Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge , no attempt has been made to quantify them . Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia . Methods Participants in a dementia trial were r and omised to intensive follow-up ( with comprehensive assessment visits at baseline and two , four and six months post r and omisation ) or minimal follow-up ( with an abbreviated assessment at baseline and a full assessment at six months ) . Our primary outcomes were cognitive functioning ( ADAS-Cog ) and participant and carer-rated quality of life ( QOL-AD ) . Results We recruited 176 participants , mainly through general practice s. The main analysis was based on Intention to treat ( ITT ) , with available data . In the ANCOVA model with baseline score as a co-variate , follow-up group had a significant effect on outcome at six months on the ADAS-Cog score ( n = 140 ; mean difference = -2.018 ; 95%CI -3.914 , -0.121 ; p = 0.037 favouring the intensive follow-up group ) , and on participant-rated quality of life score ( n = 142 ; mean difference = -1.382 ; 95%CI -2.642 , -0.122 ; p = 0.032 favouring minimal follow-up group ) . There was no significant difference on carer quality of life . Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia result ed in a better outcome than minimal follow-up , as measured by their cognitive functioning . Trial registration Current controlled trials : IS RCT OBJECTIVE Preliminary data suggest that morning bright light might improve symptoms of agitation , a serious problem in patients with dementia . The authors exp and on an earlier pilot study by evaluating the effect of bright light therapy on agitated behavior in a large sample of patients with severe dementia . METHODS Ninety-two patients were r and omly assigned to morning bright light , morning dim red light , or evening bright light . Agitation was rated by research staff who observed the patients every 15 minutes throughout the treatment period and by caregivers at one time-point before and one time-point after treatment . RESULTS Morning bright light delayed the acrophase of the agitation rhythm by over 1.5 hours . Bright light was associated with improved caregivers ' ratings but had little effect on observational ratings of agitation . CONCLUSION Although the result that light shifted the peak of the agitated behavior might be generalizable to patients with milder forms of AD , the fact that agitation was not ameliorated might not be . Because the suprachiasmatic nucleus ( SCN ) of patients with severe AD is likely to be more degenerated , and the circadian activity rhythms deteriorate as the disease progresses , it is still possible that patients with more intact SCNs , that is , patients with mild or moderate AD , might benefit from light treatment even more than those with severe AD OBJECTIVES To compare the effects of physical resistance strength training and walking ( E ) , individualized social activity ( SA ) , and E and SA ( ESA ) with a usual care control group on total nocturnal sleep time in nursing home and assisted living residents . DESIGN Pretest-posttest experimental design with assignment to one of four groups for 7 weeks : E ( n=55 ) , SA ( n=50 ) , ESA ( n=41 ) , and usual care control ( n=47 ) . SETTING Ten nursing homes and three assisted living facilities . PARTICIPANTS One hundred ninety-three residents were r and omly assigned ; 165 completed the study . INTERVENTION The E group participated in high-intensity physical resistance strength training 3 days a week and on 2 days walked for up to 45 minutes , the SA group received social activity 1 hour daily 5 days a week , the ESA group received both E and SA , and the control group participated in usual activities provided in the homes . MEASUREMENT Total nocturnal sleep time was measured using 2 nights of polysomnography before and 2 nights of polysomnography after the intervention . Sleep efficiency ( SE ) , non-rapid eye movement ( NREM ) sleep , rapid eye movement sleep , and sleep onset latency were also analyzed . RESULTS Total nocturnal sleep time was significantly greater in the ESA group than in the control group ( adjusted means 364.2 minutes vs 328.9 minutes ) , as was SE and NREM sleep . CONCLUSION High-intensity physical resistance strength training and walking combined with social activity significantly improved sleep in nursing home and assisted living residents . The interventions by themselves did not have significant effects on sleep in this population OBJECTIVES To test the effects of walking , light exposure , and a combination intervention ( walking , light , and sleep education ) on the sleep of persons with Alzheimer 's disease ( AD ) . DESIGN R and omized , controlled trial with blinded assessors . SETTING Independent community living . PARTICIPANTS One hundred thirty-two people with AD and their in-home caregivers . INTERVENTIONS Participants were r and omly assigned to one of three active treatments ( walking , light , combination treatment ) or contact control and received three or six in-home visits . MEASUREMENTS Primary outcomes were participant total wake time based on wrist actigraphy and caregiver ratings of participant sleep quality on the Sleep Disorders Inventory ( SDI ) . Secondary sleep outcomes included additional actigraphic measurements of sleep percentage , number of awakenings , and total sleep time . RESULTS Participants in walking ( P=.05 ) , light ( P=.04 ) , and combination treatment ( P=.01 ) had significantly greater improvements in total wake time at posttest ( effect size 0.51 - 0.63 ) than controls but no significant improvement on the SDI . Moderate effect size improvements in actigraphic sleep percentage were also observed in active treatment participants . There were no significant differences between the active treatment groups and no group differences for any sleep outcomes at 6 months . Participants with better adherence ( 4 d/wk ) to walking and light exposure recommendations had significantly less total wake time ( P=.006 ) and better sleep efficiency ( P=.005 ) at posttest than those with poorer adherence . CONCLUSION Walking , light exposure , and their combination are potentially effective treatments for improving sleep in community-dwelling persons with AD , but consistent adherence to treatment recommendations is required Sleep disorders are problematic for persons with dementia and their family caregivers . This r and omized controlled trial with crossover evaluated the effects of an innovative blue-white light therapy on 17 pairs of home-dwelling persons with dementia and their caregivers . Subjects with dementia received blue-white light and control ( ‘ red-yellow ’ light ) for six weeks separated by a four-week washout . Neither actigraphic nor most self-reported sleep measures significantly differed for subjects with dementia . For caregivers , both sleep and role strain improved . No evidence of retinal light toxicity was observed . Six weeks of modest doses of blue-white light appear to improve sleep in caregivers but not in persons with dementia . Greater or prolonged circadian stimulation may be needed to determine if light is an effective treatment for persons with dementia OBJECTIVES To determine whether high-intensity ambient light in public areas of long-term care facilities will improve sleeping patterns and circadian rhythms of persons with dementia . DESIGN A cluster-unit crossover intervention trial involving four conditions : morning bright light , evening bright light , all-day bright light , and minimum st and ard light . SETTING The common areas of two geriatric units in a psychiatric hospital and a dementia-specific residential care facility . PARTICIPANTS Sixty-six older adults with dementia . INTERVENTION Ambient bright light of approximately 2,500 lux , delivered through a low-glare lighting system installed in the dining and activity areas . Participant exposure averaged 2.5 to 3.0 hours for the morning and evening interventions and 8.4 hours for the all-day intervention . MEASUREMENTS Nighttime sleep using wrist actigraphy and daytime activity using nonobtrusive daytime observations . RESULTS Night-time sleep increased significantly in participants exposed to morning and all-day light , with the increase most prominent in participants with severe or very severe dementia ( mean increase 16 minutes ( P=.008 ) for morning , and 14 minutes ( P=.01 ) for all-day ) . Morning light produced a mean phase advance of 29 minutes ( P=.02 ) and evening light a mean phase delay of 15 minutes ( P=.06 ) . Effects on daytime sleepiness were inconsistent , and the number of sleep bouts , mesor , amplitude , intradaily variability , and interdaily stability were not significantly different , indicating that the overall strength of day and night activity rhythms did not change significantly under any treatment condition . CONCLUSION Bright light appears to have a modest but measurable effect on sleep in this population , and ambient light may be preferable to stationary devices such as light boxes BACKGROUND Preliminary evidence suggests that demented patients may experience beneficial effects of light therapy . The authors tested whether bright light therapy ( BLT ) is capable of improving cognitive functions in patients with Alzheimer-type dementia ( AD ) or vascular dementia ( VD ) . METHODS Twenty-three patients with AD or VD were r and omly assigned to either evening BLT or dim light therapy ( DLT ) . Effects of light therapy on cognitive functions were assessed before and after light therapy using Mini-Mental State Examination ( MMSE ) scores . Body temperature rhythm ( BTR ) was additionally recorded pre- and posttreatment . RESULTS Irrespective of their diagnosis , patients treated with BLT ( p = .0012 ) but not with DLT ( p = .73 ) showed a statistically significant increase in MMSE total scores after light therapy . Evening BLT simultaneously induced a significant phase delay of 56 min on BTR ( p = .025 ) . CONCLUSION Our preliminary results suggest that short-term evening BLT may exert beneficial effects on cognitive functioning in patients with dementia Fourteen in patients with dementia showing sleep and behavior disorders ( average age = 75 years ) , and 10 control elderly people ( average age = 75 years ) were carefully observed for 2 months . Four weeks of morning light therapy markedly improved sleep and behavior disorders in the dementia group . The measurement of sleep time and the serum melatonin values suggests that sleep and behavior disorders in the dementia group are related to decreases in the amplitude of the sleep‐wake rhythm and decreases in the levels of melatonin secretions . Morning light therapy significantly increased total and nocturnal sleep time and significantly decreased daytime sleep time . These results indicate that morning bright light is a powerful synchronizer that can normalize disturbed sleep and substantially reduce the frequency of behavior disorders in elderly people with dementia BACKGROUND Agitated behaviors are common in dementia patients residing in chronic care setting s. Their occurrence may be associated with lack of adequate exposure to sunlight and with circadian rhythm disturbances . OBJECTIVE Prior research has suggested that bright light therapy ( BLT ) may reduce agitated behaviors in dementia patients . The aim of this study was to test the efficacy of BLT in a r and omized , controlled , crossover clinical trial . METHOD Fifteen patients with dementia and agitated behaviors residing in a chronic care facility were r and omized in a crossover design to morning BLT for 1 hour per day or to a control condition with dim light exposure . Patients were treated in either condition for 4 weeks , followed by 1 week on no treatment , prior to being crossed over to the other condition . RESULTS Eight out of 15 patients completed the entire study . The rest completed at least 2 weeks of study . Patients r and omized to the BLT condition exhibited a statistically significant improvement in nocturnal sleep from a mean of 6.4 hours/night to 8.1 hours/night 4 weeks later ( p<0.05 ) . The sleep of patients in the control condition did not improve significantly . There were no other significant differences between baseline and follow-up , nor between BLT and control treated patients on the other outcome measures , which included the Behavioral Pathology in Alzheimer Disease scale ( Behave-AD ) and the Cornell Scale for Depression in Dementia . CONCLUSION Patients with dementia in chronic care who exhibit agitated behaviors sleep more hours at night when administered morning BLT . However , BLT does not lead to improvements in agitated behaviors in institutionalized patients with dementia with non-disturbed sleep-wake cycles STUDY OBJECTIVES This study evaluates the effects of bright light therapy among demented nursing home patients with sleep disturbances . DESIGN AND SETTING 11 nursing home patients with actigraphically measured sleep efficiency below 85 % took part in an open , non-r and omised study where the subjects served as their own control . INTERVENTION After two weeks of baseline measurements and two weeks of pretreatment measurements , patients received bright light exposure 2 h/day within the period 08:00 - 11:00 for two weeks . MEASUREMENTS AND RESULTS Sleep-wake patterns during the 24-h day were evaluated by nursing staff ratings and wrist-worn motor activity devices ( actigraphs ) . Sleep improved substantially with bright light exposure . Waking time within nocturnal sleep was reduced by nearly two h , and sleep efficiency improved from 73 % to 86 % . Corresponding improvements were found in nursing staff ratings . Effects were consistent across subjects . CONCLUSIONS The findings add further evidence of the effectiveness of morning bright light exposure in the treatment of disturbed sleep among demented nursing home patients The authors compared the therapeutic effect of morning bright and dim light exposure on rest-activity ( R-A ) rhythm disorders in patients with vascular dementia ( VD ) and patients with dementia of Alzheimer 's type ( DAT ) . Participants in this study were 12 patients with VD ( M/F = 5/7 ; average age = 81 years ) and 10 patients with DAT ( M/F = 4/6 ; average age = 78 years ) . They were exposed to 2 weeks of bright light ( BL ; 5000 - 8000 lux ) and 2 weeks of dim light ( DL ; 300 lux ) in the morning ( 09:00 - 11:00 ) in a r and omized crossover design in which the 2-week treatment period took place between pretreatment ( 1 week ) and posttreatment ( 1 week ) periods . Continuous R-A monitoring was performed at 1-minute intervals throughout the study using an actigraph around the nondominant wrist . The BL exposure for 2 weeks induced a significant reduction in both nighttime activity and percentages of nighttime activity to total activity compared with the pretreatment period , as well as compared with the DL condition in the VD group , but not in the DAT group . These findings support the assumption that the therapeutic efficacies of morning BL exposure are prominent in VD patients and are mainly due to its photic effect rather than nonphotic effects such as the intensification of social interaction accompanying light therapy BACKGROUND Agitation is common in people with dementia , is distressing to patients and stressful to their carers . Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate . Alternatives to drug treatment for agitation should be sought . The study aim ed to assess the effects of bright light therapy on agitation and sleep in people with dementia . METHODS A single center r and omized controlled trial of bright light therapy versus st and ard light was carried out . The study was completed prior to the m and atory registration of r and omized controls on the clinical trials registry data base and , owing to delays in writing up , retrospective registration was not completed . RESULTS There was limited evidence of reduction in agitation in people on active treatment , sleep was improved and a suggestion of greater efficacy in the winter months . CONCLUSIONS Bright light therapy is a potential alternative to drug treatment in people with dementia who are agitated OBJECTIVES To determine whether fragmented sleep in nursing home patients would improve with increased exposure to bright light . DESIGN R and omized controlled trial . SETTING Two San Diego-area nursing homes . PARTICIPANTS Seventy-seven ( 58 women , 19 men ) nursing home residents participated . Mean age + /- st and ard deviation was 85.7 + /- 7.3 ( range 60 - 100 ) and mean Mini-Mental State Examination was 12.8 + /- 8.8 ( range 0 - 30 ) . INTERVENTIONS Participants were assigned to one of four treatments : evening bright light , morning bright light , daytime sleep restriction , or evening dim red light . MEASUREMENTS Improvement in nighttime sleep quality , daytime alertness , and circadian activity rhythm parameters . RESULTS There were no improvements in nighttime sleep or daytime alertness in any of the treatment groups . Morning bright light delayed the peak of the activity rhythm ( acrophase ) and increased the mean activity level ( mesor ) . In addition , subjects in the morning bright light group had improved activity rhythmicity during the 10 days of treatment . CONCLUSION Increasing exposure to morning bright light delayed the acrophase of the activity rhythm and made the circadian rhythm more robust . These changes have the potential to be clinical ly beneficial because it may be easier to provide nursing care to patients whose circadian activity patterns are more socially acceptable BACKGROUND Neuropsychiatric symptoms ( NPS ) are prevalent in nursing-home ( NH ) patients with dementia , but little is known about the long-term course of these symptoms . METHODS In this study , 931 NH patients with dementia took part in a prospect i ve cohort study with four assessment s over a 53-month follow-up period . NPS and level of dementia were assessed with the Neuropsychiatric Inventory scale and the Clinical Dementia Rating scale , respectively . RESULTS Mild , moderate , and severe dementia was present in 25 % , 33 % , and 42 % , respectively . There was an increase in the severity of the dementia from the first to the fourth assessment . Agitation , irritability , disinhibition , and apathy were the most prevalent and persistent symptoms during the study period . The affective subsyndrome ( depression and anxiety ) became less severe , whereas the agitation subsyndrome ( agitation/aggression , disinhibition , and irritability ) and apathy increased in severity during the follow-up period . More severe dementia was associated with more severe agitation , psychosis , and apathy , but not more severe affective symptoms . Mild dementia was associated with an increase in the severity of psychosis , whereas moderate or severe dementia was associated with decreasing severity of psychosis over the follow-up period . CONCLUSION Nearly all the patients experienced clinical ly significant NPS , but individual symptoms fluctuated . Affective symptoms became less severe , while agitation and apathy increased in severity . An increase in dementia severity was associated with an increase in the severity of agitation , psychosis , and apathy , but not affective symptoms . The results may have implication s when planning evaluation , treatment , and the prevention of NPS in NH patients Sleep in the nursing home environment is extremely fragmented , possibly in part as a result of decreased light exposure . This study examined the effect of light on sleep and circadian activity rhythms in patients with probable or possible Alzheimer 's disease . Results showed that both morning and evening bright light result ed in more consoli date d sleep at night , as measured with wrist actigraphy . Evening light also increased the quality of the circadian activity rhythm , as measured by a 5-parameter extended cosine model ( amplitude , acrophase , nadir , slope of the curve , and relative width of the peak and trough ) . Increasing light exposure throughout the day and evening is likely to have the most beneficial effect on sleep and on circadian rhythms in patients with dementia . It would behoove nursing homes to consider increasing ambient light in multi purpose rooms where patients often spend much of their days Background : Bright light treatment is a therapeutic intervention mainly used to treat sleep and circadian disturbances in Alzheimer ’s disease ( AD ) patients . Recently , a h and ful of studies also focused on the effect on cognition and behavior . Conflicting findings are reported in the literature , and no definite conclusions have been drawn about its specific therapeutic effect . Summary : The aim of this review is to provide a critical evaluation of available evidence in this field , highlighting the specific characteristics of effective bright light treatment . Eligible studies were required to assess at least one of the following outcome measures : sleep , cognition , mood , and /or behavior ( e.g. , depression , agitation ) . A total of 32 articles were included in this systematic review and identified as research intervention studies about light treatment in AD . The quality of the papers was evaluated based on the US Preventive Service Task Force guidelines . Key Messages : Overall , the current literature suggests that the effects of light treatment in AD patients are mixed and may be influenced by several factors , but with a general trend toward a positive effect . Bright light seems to be a promising intervention treatment without significant adverse effects ; therefore , further well- design ed r and omized controlled trials are needed taking into account the highlighted recommendations |
10,334 | 29,150,144 | Detailed analysis of the method ologies used in the studies revealed significant variability especially regarding the sample s ' definition comparing the HPA axis activity of melancholic patients to atypical depression , including healthy controls .
While the majority of studies did confirm the association between melancholic depression and increased post-challenge cortisol levels , the association with increases in basal cortisol and basal ACTH were less consistent .
In conclusion , our findings indicate that there is a difference in the activity of the HPA-axis between melancholic and atypical depressive subtypes .
However , these are more likely explained by hypercortisolism in melancholia ; and most often normal than decreased function in atypical depression . | BACKGROUND The link between the abnormalities of the Hypothalamic-pituitary-adrenal ( HPA ) axis and depression has been one of the most consistently reported findings in psychiatry .
At the same time , multiple studies have demonstrated a stronger association between the increased activation of HPA-axis and melancholic , or endogenous depression subtype .
This association has not been confirmed for the atypical subtype , and some research ers have suggested that as an antinomic depressive subtype , it may be associated with the opposite type , i.e. hypo-function , of the HPA-axis , similarly to PTSD .
The purpose of this systematic review is to summarise existing studies addressing the abnormalities of the HPA-axis in melancholic and /or atypical depression . | The dexamethasone suppression test ( DST ) and the depressive attributional style question naire ( ASQ ) were administered to 105 depressed patients prior to participation in a double-blind outpatient study and to 29 normal controls . The depressed patients were classified into three groups ( 1 ) met criteria for both research diagnostic criteria for definite endogenous depression and DSM III melancholia ; ( 2 ) met criteria for neither , and ( 3 ) met criteria for one but not both . The group that met criteria for both RDC endogenous depression and DSM-III melancholia had a statistically greater frequency of abnormal DST versus the group that met neither criteria and the normal controls . With regard to ASQ , patients who met both criteria had statistically higher bad event internality scores but statistically lower bad event stability and globality scores as opposed to the group that met neither criteria . In general , normal controls had significantly lower bad event ASQ scores than the three depressive groups . There was no correlation between ASQ and DST , as both DST suppressors and nonsuppressors had similar ASQ scores and there was no correlation between ASQ bad event attributions and initial severity of depression BACKGROUND People with severe depressive illness have raised levels of cortisol and reduced glucocorticoid receptor function . AIMS To obtain a physiological assessment of hypothalamic-pituitary-adrenal ( HPA ) axis feedback status in an in-patient sample with depression and to relate this to prospect ively determined severe treatment resistance . METHOD The prednisolone suppression test was administered to 45 in- patients with depression assessed as resistant to two or more antidepressants and to 46 controls , prior to intensive multimodal in-patient treatment . RESULTS The patient group had higher cortisol levels than controls , although the percentage suppression of cortisol output after prednisolone in comparison with placebo did not differ . Non-response to in-patient treatment was predicted by a more dysfunctional HPA axis ( higher cortisol levels post-prednisolone and lower percentage suppression ) . CONCLUSIONS In patients with severe depression , HPA axis activity is reset at a higher level , although feedback remains intact . However , prospect ively determined severe treatment resistance is associated with an impaired feedback response to combined glucocorticoid and mineralocorticoid receptor activation by prednisolone Depressed patients have reduced glucocorticoid receptor ( GR ) function , as demonstrated by resistance to the suppressive effects of the synthetic glucocorticoid hormone , and GR agonist , dexamethasone . We have developed a suppressive test with prednisolone , a synthetic glucocorticoid that is similar to cortisol in its pharmacodynamics and pharmacokinetics , and binds to both the GR and the mineralocorticoid receptor ( MR ) . We have found that depressed patients suppress normally to prednisolone , unless they are particularly non-responsive to treatment . In the present study , we evaluated 28 in patients with treatment-resistant depression ( TRD ) , and compared salivary cortisol secretion ( at 0900 h , 1200 h and 1700 h ) after placebo or after prednisolone ( 5 mg ) , before and after an inpatient treatment admission . Half of the patients ( n=14 ) reached treatment response . When comparing the assessment between admission and discharge , cortisol output after placebo fell ( -26 % of area under the curve ; p=0.024 ) while the output after prednisolone did not change . Moreover , there was no change in the response to prednisolone ( percentage suppression ) between admission at discharge , and this was not influenced by treatment response . Finally , we could confirm and extend our previously published data with prednisolone ( 5 mg ) , showing that depressed patients ( n=12 ) and controls ( n=12 ) suppressed equally to both 5 and 10 mg doses of prednisolone . This study suggests that the response to prednisolone is similar in depressed patients and controls at different doses of prednisolone , and does not change with symptomatic improvement . This is in contrast with findings , from us and others , using other measures of hypothalamic-pituitary-adrenal axis function , such as basal cortisol levels or the response to dexamethasone . Thus , we propose that the prednisolone suppression test may offer specific biological and clinical information , related to its action at both the GR and the MR INTRODUCTION The serotonin-1A ( 5-HT1A ) receptor subtypes are considered as targets of a variety of antidepressant drugs . Previous studies have suggested different adaptive changes in pre- and post-synaptic 5-HT receptors in the brain after treatment with non-selective tricyclic antidepressants ( TCA ) and selective 5-HT re-uptake inhibitors ( SSRIs ) . The present study aim ed to investigate the adaptive effect of the TCA imipramine on the post-synaptic 5-HT1A receptor function in the hypothalamus . METHODS A longitudinal design was used in 14 patients with major depressive disorder ( DSM-IV ) with endogenous features ( Newcastle Scale ) in order to assess the functional status of post-synaptic 5-HT1A receptors before and after successful antidepressant treatment with imipramine . The effect of the 5-HT1A receptor agonist , buspirone , on ACTH , cortisol , and prolactine ( PRL ) plasma levels was used to assess the functional status of hypothalamic 5-HT1A receptors . A group of 15 concurrent normal subjects were used as control . RESULTS Endogenous depressed patients in remission and currently receiving treatment with imipramine ( mean length of treatment 145 days , SD=27 ) presented significantly lower buspirone responses to ACTH and cortisol than in the pre-treatment condition ( Deltamax p < or = .05 ; AUC p<.001 ) and to ACTH in comparison with healthy controls ( Deltamax p<.01 ; AUC p<.05 ) . No significant differences were found between the post-treatment and pre-treatment PRL responses , or between patients in both conditions and controls ; nevertheless , the PRL response in patients in remission and receiving treatment almost reached the values seen in controls . CONCLUSIONS This study extends previous findings from our group using the SSRI citalopram as an antidepressant . Imipramine and citalopram induce similar changes in the endocrine response to buspirone in depressed patients . As the direction of change in ACTH-cortisol and PRL responses after treatment is the opposite , we can not substantiate increases or decreases in the sensitivity of post-synaptic 5-HT1A receptors in the hypothalamus by long-term imipramine treatment and /or resolution of illness . Therefore , the hormonal changes may result from different or multiples unknown mechanisms Both stress-system activation and melancholic depression are characterized by fear , constricted affect , stereotyped thinking , and similar changes in autonomic and neuroendocrine function . Because norepinephrine ( NE ) and corticotropin-releasing hormone ( CRH ) can produce these physiological and behavioral changes , we measured the cerebrospinal fluid ( CSF ) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression . Plasma adrenocorticotropic hormone ( ACTH ) and cortisol levels were obtained every 30 min . Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock . Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls . Despite their hypercortisolism , depressed patients had normal levels of plasma ACTH and CSF CRH . However , plasma ACTH and CSF CRH levels in depressed patients were inappropriately high , considering the degree of their hypercortisolism . In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls , patients with depression showed no statistical relationship between these parameters . These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder . These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism . We postulate that alpha-noradrenergic blockade , CRH antagonists , and treatment with antiglucocorticoids may act at different loci , alone or in combination , in the treatment of major depression with melancholic features Rationale Patients with major depression show hypothalamic – pituitary – adrenal ( HPA ) axis hyperactivity , but the mechanisms underlying this abnormality are still unclear . Objectives We have compared two synthetic glucorticoids , dexamethasone and prednisolone , in their ability to suppress the hypothalamic – pituitary – adrenal ( HPA ) axis in depressed patients . Dexamethasone probes glucocorticoid receptor ( GR ) function , while prednisolone probes both GR and mineralocorticoid receptor ( MR ) function . Material s and methods We used a single-blind , repeated-measure design . We administered placebo , prednisolone ( 5 mg ) or dexamethasone ( 0.5 mg ) , at 22:00 , to 18 severe , treatment-resistant depressed in patients ( 15 of them with a history of childhood trauma ) and 14 healthy volunteers . On the following days , we collected salivary cortisol from 9:00 to 22:00 . Results Depressed patients had higher salivary cortisol levels compared with controls , at baseline and after both prednisolone and dexamethasone ( p<0.001 ) . Consistent with previous studies , depressed in patients showed impaired suppression by dexamethasone : based on the analysis of the areas under the curve ( AUCs ) , suppression by dexamethasone ( 0.5 mg ) was −85 % in controls vs −46 % in depressed patients ( p=0.018 ) . However , the same depressed patients showed normal suppression by prednisolone ( 5 mg ) : suppression was −41 % in controls and −36 % in depressed patients ( p=0.6 ) . Conclusions We suggest that the additional effects of prednisolone on the MR explain the different responses to these glucocorticoids in the same depressed patients BACKGROUND Depression , a clinical ly heterogeneous syndrome , may also be etiologically heterogeneous . Using a prospect i ve , epidemiologic , and genetically informative sample of adult female twins , we identify and vali date a typology of depressive syndromes . METHODS Latent class analysis was applied to 14 disaggregated DSM-III-R symptoms for major depression reported over the last year by members of 1029 female-female twin pairs . RESULTS Seven classes were identified , of which 3 represented clinical ly significant depressive syndromes : ( 1 ) mild typical depression , ( 2 ) atypical depression , and ( 3 ) severe typical depression . Severe typical depression was characterized by comorbid anxiety and panic , long episodes , impairment , and help seeking . Atypical depression was similar in severity to mild typical depression , but was characterized by increased eating , hypersomnia , frequent , relatively short episodes , and a proclivity to obesity . Individuals with recurrent episodes tended to have the same syndrome on each occasion . The members of twin pairs concordant for depression had the same depressive syndrome more often than expected by chance and this resemblance was greater in monozygotic than in dizygotic pairs . CONCLUSION In an epidemiologic sample of female twins , depression is not etiologically homogeneous , but is instead made up of several syndromes that are at least partially distinct from a clinical , longitudinal , and familial/genetic perspective We summarise a series of studies using a MAOI to help establish the validity of a subgroup of depressives referred to as atypical depressives . Patients with reactive mood meeting DSM-III criteria for depressive illness who had associated atypical features ( which include hyperphagia , hypersomnolence , leaden paralysis , and rejection sensitivity ) were r and omised to imipramine , phenelzine and placebo . Non-responders were crossed over , and in all there were over 400 patient trials . Phenelzine consistently was found to be superior to imipramine . Only in trials which included patients lacking atypical , vegetative symptoms was imipramine found to equal phenelzine . We conclude that the research er and the clinician should consider the relevance of the atypical depressive syndrome Depression may be associated with a hypofunction of central serotonergic systems . The prolactin response to fenfluramine , an indicator of serotonergic activity , has been reported to be blunted in depressed patients compared to controls . It has also been suggested that blunting is more likely in melancholic depression . Baseline cortisol , prolactin and tryptophan availability have also been suggested to affect this response . Forty-eight men and 61 women with a major depressive episode , and who were drug free , and 20 healthy control men underwent clinical evaluation and fenfluramine challenge with dl-fenfluramine 1 mg/kg . When baseline variables were covaried , there was no difference in prolactin response to fenfluramine between males with depression and age-matched controls . Amongst all the depressed patients , body mass index showed a significant association with prolactin response to fenfluramine . There was an interaction between baseline cortisol and DSM-III-R melancholic subtype of depression whereby non-melancholic patients appeared more likely to increase prolactin response to fenfluramine in response to higher cortisol levels . Prolactin response to fenfluramine was not blunted in major depression and there was no difference between melancholic and non-melancholic depression . However , the relationship between prolactin response to fenfluramine and baseline cortisol levels appeared to differ between these two subtypes of depression OBJECTIVE To examine if atypical depression may be associated with hypersuppression of the hypothalamic-pituitary-adrenal ( HPA ) axis . METHOD Eight women with atypical major depression and 11 controls with no history of psychiatric illness , matched on age and body mass index , were challenged with low-dose dexamethasone ( 0.25 mg and 0.50 mg in r and om order and 1 week apart ) . Dexamethasone was self administered at 11 pm , and plasma cortisol sample s were drawn at 8 am and 3 pm on the following day . RESULTS After the 0.50-mg dexamethasone challenge , mean suppression of morning cortisol was significantly greater in patients with atypical depression ( 91.9 % , st and ard deviation [ SD ] 6.8 % ) than in the controls ( 78.3 % , SD 10.7 % ; p < 0.01 ) . CONCLUSION These preliminary data add to the growing body of literature that suggests atypical depression , in contrast to classic melancholia , may be associated with exaggerated negative feedback regulation of the HPA axis Individuals with bulimia nervosa ( BN ) have a very high lifetime prevalence of major depression ( Hatsukami et al 1984 ; Hudson et al 1987 ) , an important consideration when interpreting biological studies in BN . Another potential issue is that many BN patients experience " reversed symptoms " such as hypersomnia and hyperphagia when depressed ( Lam et al 1991 ) ; to date , there is a dearth of research on possible neuroendocrine changes associated with these " reversed " symptoms . We report here an unanticipated finding of a strong negative relationship between plasma cortisol levels and " reversed " symptoms of depression , in particular hypersomnia and carbohydrate craving , in a small sample of BN patients |
10,335 | 25,530,293 | DISCUSSION With CATCH it is possible to categorize and underst and the mechanisms that can trigger a change in behavior in health care providers . | INTRODUCTION There is little guidance available on strategies to improve the communication quality of printed educational material s ( PEMs ) for clinicians .
The purpose s of this study were to conceptualize PEM communication quality , develop a checklist based on this conceptualization , and vali date the checklist with a selection of PEMs . | Objectives : To determine whether writing clinical guideline recommendations in behaviourally specified “ plain English ” language increases the likelihood of their implementation by service users ( patients ) . Design : R and omised controlled trial in which participants received either the original text of the National Institute for Clinical Excellence ( NICE ) public guidelines for the management of schizophrenia or a behaviourally specified text with the same content . Setting : Mental health service user networks and voluntary sector organisations within two inner London boroughs . Participants : Eighty four mental health service users recruited by post or face to face contact at service user meetings . Intervention : The section of the NICE public guidelines for schizophrenia concerning psychological and pharmacological treatments was rewritten to improve style and behavioural specificity by applying evidence -based and psychologically informed principles of good written communication . Outcome measures : Cognitive predictors of behaviour , as specified by the evidence based theory of planned behaviour , constituted the primary outcome as it was not possible to measure the actual behaviour of guideline implementation . The predictors were behavioural intentions to implement the guidelines , attitudes towards implementation , and perceived behavioural control over implementation . Satisfaction with the guidelines and perceived comprehension were also measured . Results : Behaviourally specified “ plain English ” guidelines led to stronger intentions to implement the guidelines , more positive attitudes towards them , and greater perceived behavioural control over using them . There was no difference in satisfaction or perceived comprehension . Conclusions : Writing guidelines with high behavioural specificity in conjunction with the use of “ plain English ” may be a simple and effective method of increasing their implementation . Evaluation with a behavioural outcome is now needed 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 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 This paper describes a model , derived from subjective expected utility ( SEU ) theory , which attempts to explain the effects of a fear-arousing communication about smoking and lung cancer on smokers ' decisions to try to stop smoking . According to the model , the strength of the smoker 's intention to try to stop smoking will depend on three factors : ( 1 ) the utility of lung cancer ; ( 2 ) the perceived reduction in the risk of getting lung cancer that follows from successfully stopping smoking ( probability difference ) ; and ( 3 ) the subjective probability of successfully stopping smoking , or confidence . The usefulness of this model vis-à-vis one based on the amount of fear aroused by the communication was investigated in two experimental studies conducted in the field in which smokers watched either a videotape about smoking or one on a different health topic . The smoking videotape influenced not only attitudes and beliefs measured immediately after exposure but also subsequent self-reports of behavior ( whether or not the subject tried to stop smoking or to cut down in the 3-month period following exposure to the videotape ) . In accordance with predictions , the three variables specified by the model together affected intention to try to stop smoking , which in turn affected behavior . The effect of confidence on intention was relatively large . There was no evidence for the multiplicative combination of utilities and subjective probabilities predicted by a strict SEU model . Contrary to the predictions of the model , but consistent with previous research , the amount of fear aroused by the videotape had an independent effect on intention , suggesting that explanations of the effects of fear-arousing communications will have to incorporate both cognitive and emotional mediation processes Background Efficacious strategies for the primary prevention of coronary heart disease ( CHD ) are underused , and , when used , have low adherence . Existing efforts to improve use and adherence to these efficacious strategies have been so intensive that they are impractical for clinical practice . Methods We conducted a r and omized trial of a CHD prevention intervention ( including a computerized decision aid and automated tailored adherence messages ) at one university general internal medicine practice . After obtaining informed consent and collecting baseline data , we r and omized patients ( men and women age 40 - 79 with no prior history of cardiovascular disease ) to either the intervention or usual care . We then saw them for two additional study visits over 3 months . For intervention participants , we administered the decision aid at the primary study visit ( 1 week after baseline visit ) and then mailed 3 tailored adherence reminders at 2 , 4 , and 6 weeks . We assessed our outcomes ( including the predicted likelihood of angina , myocardial infa rct ion , and CHD death over 10 years ( CHD risk ) and self-reported adherence ) between groups at 3 month follow-up . Data collection occurred from June 2007 through December 2009 . All study procedures were IRB approved . Results We r and omized 160 eligible patients ( 81 intervention ; 79 control ) and followed 96 % to study conclusion . Mean predicted CHD risk at baseline was 11.3 % . The intervention increased self-reported adherence to chosen risk reducing strategies by 25 percentage points ( 95 % CI 8 % to 42 % ) , with the biggest effect for aspirin . It also changed predicted CHD risk by -1.1 % ( 95 % CI -0.16 % to -2 % ) , with a larger effect in a pre-specified subgroup of high risk patients . Conclusion A computerized intervention that involves patients in CHD decision making and supports adherence to effective prevention strategies can improve adherence and reduce predicted CHD risk . Clinical trials registration number Clinical Trials.gov : BACKGROUND : Providing antidepressant information to patients may foster greater adherence to therapy . OBJECTIVE : To assess physician information-giving while prescribing antidepressants , and to identify factors that influence the provision of information . DESIGN : R and omized experiment using st and ardized patients ( SPs ) . St and ardized patients roles were generated by crossing 2 clinical conditions ( major depression or adjustment disorder ) with 3 medication request types ( br and -specific , general , or none ) . PARTICIPANTS : One hundred and fifty-two general internists and family physicians recruited from solo and group practice s and health maintenance organizations ; cooperation rates ranged from 53 % to 61 % . MEASUREMENTS : We assessed physician information-giving by analyzing audio-recordings of interactions between physicians and SPs , and collected physician background information by survey . Generalized estimating equations were used to examine the influence of patient and physician factors on physicians ’ provision of information . RESULTS : One hundred and one physicians prescribed antidepressants , accounting for 131 interactions . The mean age of physicians was 46.3 years : 69 % were males . Physicians mentioned an average of 5.7 specific topics of anti-depressant-related information ( of a possible maximum of 11 ) . The most frequently mentioned topic was purpose ( 96.1 % ) . Physicians infrequently provided information about the duration of therapy ( 34.9 % ) and costs ( 21.4 % ) . St and ardized patients who presented with major depression received less information than those with adjustment disorder , and older and solo/private practice physicians provided significantly less information to SPs . CONCLUSIONS : Physicians provide limited information to patients while prescribing antidepressants , often omitting critical information that may promote adherence . Mechanisms are needed to ensure that patients receive pertinent antidepressant information Printed health education material s ( HEMs ) are widely used to increase awareness and knowledge , change attitudes and beliefs , and help individuals adopt and maintain healthy lifestyle behaviors . While much of the contemporary research and development of persuasive communication is based on McGuire 's input/output model , to date few studies have compared the impact of a large set of inputs across a comprehensive set of the 12 outputs . We examined the effects of printed HEMs on weight loss on the cognitive , affective , and behavioral responses of 198 overweight adults . Participants were recruited via a newspaper advertisement and were r and omly assigned to review one of three HEMs . Participants were interviewed and asked to complete a series of question naires both before and after viewing the HEMs . Regression analyses were conducted to identify the input characteristics associated with success at each of the output steps . The results revealed attractiveness , encouragement , level of information , and application to one 's life were significantly associated with early steps ( attention , liking , and underst and ing ) as well as some of the mediating steps ( recalling , keeping , and rereading HEMs ) . Later steps , such as intention to change behavior and show others , were associated with readiness to change , self-efficacy , and perceived application to one 's life . Behavior change was more likely for those who received tailored material s and those who had higher self-efficacy . These results provide useful direction for the use of computers in tailoring the content of HEMs and the development of effective communication of health information on weight loss BACKGROUND Physicians often search for information to improve patient care . We evaluated how nephrologists use online information sources for this purpose . METHODS In this cross-sectional study ( 2008 to 2010 ) , a r and om sample of Canadian nephrologists completed a survey of their online search practice s. We queried respondents on their search ing preferences , practice s and use of 9 online information sources . RESULTS Respondents ( n=115 ; 75 % response rate ) comprised both academic ( 59 % ) and community-based ( 41 % ) nephrologists . Respondents were an average of 48 years old and were in practice for an average of 15 years . Nephrologists used a variety of online sources to retrieve information on patient treatment including UpTo Date ( 92 % ) , PubMed ( 89 % ) , Google ( 76 % ) and Ovid MEDLINE ( 55 % ) . Community-based nephrologists were more likely to consult UpTo Date first ( 91 % ) , while academic nephrologists were divided between UpTo Date ( 58 % ) and PubMed ( 41 % ) . When search ing bibliographic re sources such as PubMed , 80 % of nephrologists scan a maximum of 40 citations ( the equivalent of 2 search pages in PubMed ) . Search ing practice s did not differ by age , sex or years in practice . CONCLUSIONS Nephrologists routinely use a variety of online re sources to search for information for patient care . These include bibliographic data bases , general search engines and specialized medical re sources The seven articles in this issue , and the accompanying meta- analysis in Health Psychology Review [ McEachan , R.R.C. , Conner , M. , Taylor , N. , & Lawton , R.J. ( 2011 ) . Prospect i ve prediction of health-related behaviors with the theory of planned behavior : A meta- analysis . Health Psychology Review , 5 , 97–144 ] , illustrate the wide application of the theory of planned behaviour [ Ajzen , I. ( 1991 ) . The theory of planned behavior . Organizational Behavior and Human Decision Processes , 50 , 179–211 ] in the health domain . In this editorial , Ajzen reflects on some of the issues raised by the different authors . Among the topics addressed are the nature of intentions and the limits of predictive validity ; rationality , affect and emotions ; past behaviour and habit ; the prototype/willingness model ; and the role of such background factors as the big five personality traits and social comparison tendency |
10,336 | 26,680,609 | A range of school-based policy ( e.g. break time length ) , physical ( e.g. facilities ) and social-environmental ( e.g. teacher behaviours ) factors were associated with adolescent physical activity , with limited research on sedentary behaviour .
The mixed- studies synthesis revealed the importance of specific activity setting s ( type and location ) and intramural sport opportunities for all students .
Important physical education-related factors were a mastery-oriented motivational climate and autonomy supportive teaching behaviours .
Qualitative evidence highlighted the influence of the wider school climate and shed light on complexities of the associations observed in the quantitative literature . | There is increasing academic and policy interest in interventions aim ing to promote young people 's health by ensuring that the school environment supports healthy behaviours .
The purpose of this review was to summarize the current evidence on school-based policy , physical and social-environmental influences on adolescent physical activity and sedentary behaviour . | OBJECTIVES We sought to determine the association between school- and neighborhood-level characteristics and physical activity among young people . METHODS We collected the data as part of Youth'07 , a nationally representative survey of the health and well-being of high school students in New Zeal and . In total , 9107 students from 96 schools participated ( 63 % response rate ) . Students answered questions about their schools ( e.g. , support for physical activity ) and neighborhoods ( e.g. , community cohesion , disintegration , safety , and recreational facilities ) . We created school-level measures by aggregating the students ' reports within their schools and we created neighborhood-level measures by aggregating the students ' reports of their neighborhoods to the census area unit of their residential address . We conducted analyses by using cross-classified r and om-effects models controlling for individual variables , with school and neighborhoods treated as r and om effects . RESULTS Schools characterized by high sports team participation and neighborhoods characterized by high social connections were positively associated with student physical activity . We observed few other significant characteristics of school and neighborhood environments . CONCLUSIONS Our findings highlight that opportunity for sports participation and strong social connections in neighborhoods are particularly important for youths ' physical activity 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 Background Regular physical activity is associated with a range of physical and psychological health benefits . In North America the majority of adolescents are insufficiently active . Purpose The purpose of this study was to examine the prospect i ve relationship between adolescents ' perceptions of transformational leadership displayed by their school physical education teachers and their own physical activity behaviors , both with respect to within-class physical activity ( WCPA ) and also leisure time physical activity ( LTPA ) . Method The study used a prospect i ve observational design . Using multilevel structural equation modeling ( MSEM ) , we examined the extent to which adolescents ' affective attitudes mediated the effects of teachers ' behaviors on adolescents ' physical activity responses . Two thous and nine hundred and forty-eight adolescents ( Mage = 14.33 , SD = 1.00 , Nfemale = 1,641 , 55.7 % ) from 133 Grade 8–10 classes in British Columbia ( Canada ) provided ratings of their physical education teachers ' behaviors midway through the school year . Two months later , students completed measures of affective attitudes , WCPA , and LTPA . Results The results indicated that adolescents ' perceptions of transformational teaching explained significant variance in both WCPA and LTPA , and these effects were fully mediated by adolescents ' affective attitudes ( total indirect effect : b = 0.581 , p < 0.001 ) . Conclusion The findings suggest that transformational leadership behaviors displayed by physical education teachers may be an important source of adolescent enjoyment of physical education as well as health-enhancing physical activity involvement within school and outside of school PURPOSE To examine the relationship between role model presence , type of role model , and various health-risk and health-protective behaviors among California adolescents . METHODS We used cross-sectional data on 4,010 multiethnic adolescents aged 12 - 17 years from the 2003 California Health Interview Survey , a population -based r and om-digit dial telephone survey of more than 40,000 California households . The survey , conducted every other year since 2001 , collects extensive demographic , health , and health-related information . RESULTS Fifty-nine percent of adolescents identified a role model . Affluent teens were more likely to have a role model than lower income teens . Role models were generally of the same ethnicity and gender as the teens ; ethnic congruence was higher among African Americans and whites than Latinos and Asians ; gender congruence was higher among males . Type of role model was significantly associated with health-related behaviors . Identification of a teacher was strongly associated with positive health behaviors . Correlations with health-promoting behaviors were generally smaller in magnitude but consistently positive among family member and athlete role models . Peer or entertainer role models were associated with health-risk behaviors . CONCLUSION Not only role model presence but also the type of role model is an important predictor of adolescent health-related behaviors . Our findings have implication s for design ing youth targeted interventions and policies involving role models Within instructional setting s , individuals form relational efficacy appraisal s that complement their self-efficacy beliefs . In high school physical education ( PE ) , for instance , students develop a level of confidence in their teacher 's capabilities , as well as estimating how confident they think their teacher is in their ( i.e. , the students ' ) ability . Grounded in existing trans context ual work , we examined the motivational pathways through which students ' relational efficacy and self-efficacy beliefs in PE were predictive of their leisure-time physical activity . Singaporean students ( N = 990 ; age M = 13.95 , SD = 1.02 ) completed instruments assessing efficacy beliefs , perceptions of teacher relatedness support , and autonomous motivation toward PE , and 2 weeks later they reported their motivation toward , and engagement in , leisure-time physical activity . Structural equation modeling revealed that students reported stronger other-efficacy and RISE beliefs when they felt that their teacher created a highly relatedness-supportive environment . In turn , their relational efficacy beliefs ( a ) supported their confidence in their own ability , ( b ) directly and indirectly predicted more autonomous motives for participation in PE , and ( c ) displayed prospect i ve trans context ual effects in relation to leisure-time variables . By emphasizing the adaptive motivational effects associated with the tripartite constructs , these findings highlight novel pathways linking students ' efficacy perceptions with leisure-time outcomes Objective To examine associations between students ’ time spent in moderate to vigorous physical activity ( MVPA ) and the school built environment while also considering features of the schools ’ social environment and student-level characteristics . Methods Using surveys and GIS measures , multilevel linear regression analysis was applied to examine the environment- and student-level characteristics associated with time spent in MVPA among grade 9–12 students ( n = 22,117 ) attending 76 secondary schools in Ontario , Canada as part of the SHAPES-Ontario study . Results Statistically significant between-school r and om variation in student MVPA was identified [ $ $ \sigma^{2}_{\mu 0 } $ $ = 9,065.22 ( 250.64 ) ] ; school-level differences accounted for 3.0 % of the variability in student MVPA . Students attending a school that offered daily physical education or provided an alternate room for physical activity spent more time in MVPA than students attending a school without these re sources . Moreover , as l and -use mix diversity and walkability of the school neighbourhood increased , students ’ time spent in MVPA decreased . Conclusion Developing a better underst and ing of the environment- and student-level characteristics associated with students ’ time spent in MVPA is critical for informing school-based physical activity intervention programmes and policies 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 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 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 The relationship between the school environment and health has infrequently been examined . This study sought to examine the association between school students ' perceptions of their school environment , teachers ' and peers ' support and their health behaviours . A cross sectional descriptive survey by supervised self-administration was conducted in 1996 based on the international WHO collaborative survey of school children 's health and lifestyle ( the HBSC Study ) and extended in an Australian setting . R and omly sample d primary and secondary schools from Catholic , Independent and Government education sectors throughout New South Wales ( NSW ) , Australia , were invited to participate . The final sample included 3918 school students attending Year 6 ( primary school ) , Year 8 and Year 10 ( high school ) from 115 schools . The main outcome measures were self-reported health status and 7 health behaviours ( tobacco use , alcohol use , physical activity , dental hygiene , nutritional intake , seat belt and bicycle helmet use ) . Independent variables included student perceptions of the school environment , perceptions of teachers ' and peers ' support . Girls , Year 6 students and students who have less than $ 19 a week to spend were significantly more likely to have positive perceptions towards their school environment , teacher(s ) and peers . Students who had positive perceptions regarding their school environment and perceived their teachers as supportive were significantly more likely to engage in health promoting behaviours adjusting for age , sex and average weekly pocket money . A supportive peer environment was not associated with positive health behaviour . Health promotion practitioners need to consider the impact of the school environment on health behaviours of school students . In particular , practitioners should consider intervention models that improve the school environment as a key strategy within a health promoting school Objective : To assess developmental trends in physical activity and sedentary behaviour in British adolescents in relation to sex , ethnicity and socioeconomic status ( SES ) . Design : A 5-year longitudinal study of a diverse cohort of students aged 11–12 years at baseline in 1999 . Setting : 36 London schools sample d using a stratified r and om sampling procedure . Participants : A total of 5863 students categorised as white , black or Asian , and stratified for SES using the Townsend Index . Main outcome measures : Number of days per week of vigorous activity leading to sweating and breathing hard . Hours of sedentary behaviour , including watching television and playing video games . Data were analysed using multilevel , linear , mixed models . Results : Marked reductions in physical activity and increases in sedentary behaviour were noticed between ages 11–12 and 15–16 years . Boys were more active than girls , and the decline in physical activity was greater in girls ( 46 % reduction ) than in boys ( 23 % ) . Asian students were less active than whites , and this was also true of black girls but not boys . Black students were more sedentary than white students . Levels of sedentary behaviour were greater in respondents from lower SES . Most differences between ethnic and SES groups were present at age 11 years , and did not evolve over the teenage years . Conclusions : Physical activity declines and sedentary behaviour becomes more common during adolescence . Ethnic and SES differences are observed in physical activity and sedentary behaviour in British youth that anticipate adult variations in adiposity and cardiovascular disease risk . These are largely established by age 11–12 years , so reversing these patterns requires earlier intervention OBJECTIVE Physical education ( PE ) programs aim to promote physical activity ( PA ) and reach most school-aged youth . However , PA levels within PE lessons are often low . In this cluster-r and omized controlled trial , we examined the effects of three self-determination theory-based motivational strategies on PA and sedentary behavior , as well as their hypothesized antecedents during PE lessons . METHODS Data were collected in Sydney , Australia ( October-December 2011 ) . After baseline testing , teachers ( n=16 ) and their classes ( n=288 students ; M=13.6 years , 50.4 % male ) were r and omly assigned to one of four teaching strategy conditions : ( 1 ) explaining relevance ; ( 2 ) providing choice ; ( 3 ) complete free choice ; or ( 4 ) usual practice . Teachers then delivered the assigned strategy . Primary outcomes were accelerometer-assessed PA and student motivation during lessons . Secondary outcomes included sedentary behavior , perceptions of teachers ' support and psychological needs satisfaction . RESULTS The ' free choice ' intervention increased PA ( p<.05 ) . ' Providing choice ' and ' free choice ' interventions decreased sedentary behavior ( p<.05 ) . The interventions did not influence motivation , but students ' autonomy increased during both choice-based interventions ( p<.05 ) . CONCLUSIONS Promoting choice can produce short-term increases in PA and decreases in sedentary behavior , as well as increased perceived autonomy during PE lessons Childhood obesity is a public health concern with significant health and economic impacts . We conducted a prospect i ve experimental study in 4 classrooms in central Texas to determine the effect of desks that encourage st and ing rather than sitting on caloric expenditure in children . Students were monitored with calorie expenditure-measuring arm-b and s worn for 10 days in the fall and spring . The treatment group experienced significant increases in calorie expenditure over the control group , a finding that has implication s for policy and practice |
10,337 | 28,802,291 | Because of the poor method ological quality and high risk of bias in the included studies , this systematic review revealed no definite conclusion about the application of metoclopramide for the reduction of nosocomial pneumonia . | BACKGROUND AND OBJECTIVES Metoclopramide , a prokinetic agent , has been recommended to reduce incidence of pneumonia , but its efficacy is controversial .
Thus , this systematic review aim ed to evaluate the effectiveness of metoclopramide for pneumonia in patients fed via nasogastric tube . | Background and Purpose — Pneumonia is a major cause of mortality and morbidity in patients with stroke fed via nasogastric tubes and may be because of vomiting and gastro-oesophageal regurgitation . The aim of the study was to assess whether regular treatment with metoclopramide , a D2-receptor antagonist with antiemetic and gastric prokinetic actions , could reduce the rate of aspiration and pneumonia . Methods — Patients with no signs of pneumonia within 7 days of stroke onset and 48 hours of insertion of a nasogastric tube were recruited into a double-blind r and omized placebo-controlled trial . Participants received metoclopramide 10 mg or placebo 3 × daily via the nasogastric tube for 21 days or until nasogastric feeds were discontinued . Clinical signs of pneumonia were recorded daily . Pneumonia was diagnosed if the patient had relevant clinical signs , high inflammatory markers , and new infiltrates on the chest radiograph . Results — Sixty patients ( mean age , 78 years ; 38 women ; mean National Institutes for Health Stroke Scale score , 19.25 ) were r and omized in a 1:1 ratio . There were significantly more episodes of pneumonia in the placebo group than in the metoclopramide group ( rate ratio , 5.24 ; P<0.001 ) . There were also significant differences in favor of metoclopramide in the rate of aspiration , oxygen saturation , highest inflammatory markers , and National Institutes for Health Stroke Scale . There was no significant difference in mortality between the groups . Conclusions — This study suggests that metoclopramide may reduce the rate of pneumonia and may improve other clinical outcomes in patients with subacute stroke fed via nasogastric tube . These findings need to be confirmed in larger r and omized and blinded trials . Clinical Trial Registration — URL : https://www . clinical trialsregister.eu . EudraCT no : 2006 - 002570 - 22 , URL : http://www.controlled-trials.com/IS RCT N18034911/18034911 Purpose This study aim ed to determine if preoperative oral administration of metoclopramide , chlorpromazine , gabapentin , or dexamethasone would effectively reduce postoperative nausea and vomiting ( PONV ) in the first 24 hours after surgery in patients undergoing maxillofacial trauma surgery . Methods One hundred fifty patients with maxillofacial skeletal trauma that need open reduction and internal fixation were r and omly assigned to receive one of the fallowing drugs orally , 1 hour preoperative : 10 mg metoclopramide ( group A ) , 300 mg gabapentin ( group B ) , 100 mg chlorpromazine ( group C ) , 5 mg dexamethasone ( group D ) , and placebo ( group E ) . All patients were observed in the first 24 hours for PONV . Data analysis was done with the SPSS software ( version 19 ) , using chi-square test , Fisher exact test , and multiple logistic regression methods . Results The incidence of vomiting was significantly lower in groups A ( 2/30 ) , B ( 3/30 ) , and C ( 2/30 ) compared with the placebo group ( 9/30 ) ( P < 0.05 ) . Also , the incidence of postoperative nausea was significantly high in the placebo group ( 11/30 ) as compared to treatment groups A ( 2/30 ) , B ( 3/30 ) , and C ( 3/30 ) ( P < 0.05 ) . No significant differences in the incidence of PONV were found between groups D ( 7/30 ) and E ( P > 0.05 ) . Of all demographic variables , anesthesia time ( P = 0.034 ) and surgery time ( P = 0.047 ) were predictors of PONV . Conclusion Our results demonstrated that premedication with oral metoclopramide , gabapentin , or chlorpromazine can significantly decrease the incidence of PONV in patients undergoing maxillofacial trauma surgery 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 Ventilator associated pneumonia is a major cause of morbidity in the intensive care unit . Difficulties in identification of the risk factors , in diagnosing and in prevention , have intensified the problem . OBJECTIVES To measure the incidence of ventilator associated pneumonia in intensive care unit and to identify the risk factors associated . METHODS A prospect i ve observational cohort study was done in which we evaluated 69 patients who were mechanically ventilated for more than 48 hours to find out the development of nosocomial pneumonia and presence or absence of risk factors . Data were subjected to univariate analysis using chi-square and t-test . Level of significance was set at 0.05 . RESULTS Twenty two ( 31.88 % ) out of 69 patients developed ventilator associated pneumonia , majority of them between four days to 14 days . Reintubation , invasive lines , H2 blockers and low PaO2/FiO2 were identified as major risk factors in our study . Enteral feeding via nasogastric tube and use of steroids was not associated with development of ventilator associated pneumonia . The patients with ventilator associated pneumonia had significantly longer duration of mechanical ventilation ( 18.88+/-7.7 days vs 7.36+/-4.19 days ) and stay ( 29+/-17.8 days vs 9.22+/-5.14 days ) . The morality was similar for both the groups with or without ventilator associated pneumonia . CONCLUSION The incidence of ventilator pneumonia is high . Patients requiring prolonged ventilation , re-intubation , more invasive lines and H2 blockers , are at high risk and need special attention towards prevention BACKGROUND AND OBJECTIVE Unguided nasojejunal feeding tube insertion success rates are low . Controversy persists about how to safely and efficiently perform enteral nutrition ( EN ) in critically ill patients . This study explores an innovative blind nasointestinal tube ( NIT ) insertion method and compares nasogastric and nasointestinal feeding . METHODS Seventy critically ill patients admitted to the intensive care unit ( ICU ) were divided r and omly into a nasogastric tube group ( NGT ; n=35 ) and an NIT group ( NIT ; n=35 ) . After bedside NGT and blind-type NIT insertion , tube position was assessed and EN was started on day 1 . Patients ' nutritional status parameters , mechanical ventilation duration , average ICU stay , nutritional support costs , and feeding complications were compared . RESULTS Pre-albumin and transferrin levels on days 7 and 14 were significantly higher in the NIT group than in the NGT group ( p<0.01 , p<0.05 ) . Bloating , diarrhea , upper gastrointestinal bleeding , and liver damage did not differ significantly between groups ( p>0.05 ) . Interleukin-6 and tumor necrosis factor-α levels and APACHE II score were significantly lower in the NIT group than in the NGT group ( p<0.01 , p<0.05 ) . Reflux and pneumonia incidences , mechanical ventilation duration , average ICU stay length , and nutritional support costs were significantly lower in the NIT group than in the NGT group ( p<0.01 ) . CONCLUSION Blind bedside NIT insertion is convenient and its use can effectively improve nutritional status , reduce feeding complications , and decrease nutritional support costs of critically ill patients Background There are numerous challenges in providing nutrition to the mechanically ventilated critically ill ICU patient . Underst and ing the level of nutritional support and the barriers to enteral feeding interruption in mechanically ventilated patients are important to maximise the nutritional benefits to the critically ill patients . Thus , this study aims to evaluate enteral nutrition delivery and identify the reasons for interruptions in mechanically ventilated Malaysian patients receiving enteral feeding . Methods A cross sectional prospect i ve study of 77 consecutive patients who required mechanical ventilation and were receiving enteral nutrition was done in an open 14-bed intensive care unit of a tertiary hospital . Data were collected prospect ively over a 3 month period . Descriptive statistical analysis were made with respect to demographical data , time taken to initiate feeds , type of feeds , quantification of feeds attainment , and reasons for feed interruptions . There are no set feeding protocol s in the ICU . The usual initial rate of enteral nutrition observed in ICU was 20 ml/hour , assessed every 6 hours and the decision was made thereafter to increase feeds . The target calorie for each patient was determined by the clinician alongside the dietitian . The use of prokinetic agents was also prescribed at the discretion of the attending clinician and is commonly IV metoclopramide 10 mg three times a day . Results About 66 % of patients achieved 80 % of caloric requirements within 3 days of which 46.8 % achieved full feeds in less than 12 hours . The time to initiate feeds for patients admitted into the ICU ranged from 0 – 110 hours with a median time to start feeds of 15 hours and the interquartile range ( IQR ) of 6–59 hours . The mean time to achieve at least 80 % of nutritional target was 1.8 days ± 1.5 days . About 79 % of patients experienced multiple feeding interruptions . The most prevalent reason for interruption was for procedures ( 45.1 % ) followed by high gastric residual volume ( 38.0 % ) , diarrhoea ( 8.4 % ) , difficulty in nasogastric tube placement ( 5.6 % ) and vomiting ( 2.9 % ) . Conclusion Nutritional inadequacy in mechanically ventilated Malaysian patients receiving enteral nutrition was not as common as expected . However , there is still room for improvement with regards to decreasing the number of patients who did not achieve their caloric requirement throughout their stay in the ICU OBJECTIVES To investigate the absorption of the gastrokinetic drug , cisapride , and effect of cisapride on gastric emptying in critically ill patients ; and to assess the usefulness of clinical signs of gastric emptying . DESIGN Prospect i ve , r and omized , controlled study . SETTING Medical/surgical/trauma intensive care unit ( ICU ) in a university hospital . PATIENTS Twenty-seven consecutively enrolled patients , aged 18 to 65 yrs , with normal hepatic and renal biochemistry who were not receiving enteral nutrition and who had no contraindications to enteral nutrition . These patients were expected to stay in the ICU for at least 4 days . INTERVENTIONS Patients were r and omized to receive either placebo or rectal cisapride , 60 mg initially followed by two doses of 30 mg at 8-hr intervals . MEASUREMENTS AND MAIN RESULTS Gastric emptying was estimated , using acetaminophen absorption on day 1 of the study . Placebo or cisapride was administered and a second acetaminophen absorption test for gastric emptying was carried out on day 2,24 hrs after the first test . Four patients were excluded because of incomplete data . Statistical analysis was performed , using the area under the acetaminophen absorption curve from 0 to 60 mins as the primary measure of gastric emptying . There was no significant change in the area under the acetaminophen absorption curve from 0 to 60 mins from day 1 to day 2 in patients who received placebo or cisapride . Using the combination of the time to maximum acetaminophen concentration ( < or = 30 mins ) with a maximum concentration ( > 12 mg/L ) to define " normal " emptying , on day 1 , four of the 11 placebo patients had the " normal " gastric emptying , and by day 2 , five patients fulfilled this criterion . Before administration of cisapride , four of the 12 patients fulfilled this criterion , whereas nine fulfilled the criterion after receiving cisapride . There was a large variation in gastric emptying from day 1 to day 2 ; a power calculation suggests that approximately 150 patients would have to be studied to determine the effect of cisapride . There was no correlation between gastric emptying and the volume of gastric aspirate or the presence of bowel sounds . Plasma cisapride concentrations 4 hrs after the third dose , during the second acetaminophen absorption test , averaged 53 ng/mL ( range 20 to 111 ) . CONCLUSIONS Rectal cisapride in the dose given achieved average plasma concentrations similar to those concentrations achieved in healthy subjects after 30 mg of cisapride rectally . There is a large variation in gastric emptying from one day to the next and large numbers of patients are required to determine if cisapride administration improves early gastric emptying in critically ill patients . The volume of gastric aspirate and the presence of bowel sounds do not correlate with gastric emptying PURPOSE The prupose was to identify , through the BreathID automatic breath-testing device , the best prokinetic therapy to enhance gastric-emptying rate ( GER ) in ventilated intensive care unit patients . MATERIAL S AND METHODS This was a prospect i ve , crossover , nonr and omized study . Consecutive ventilated patients who could be fed enterally and expected to require 5 days of ventilation were included . (13)C-labeled-acetate in 100 mL Osmolite ( BreathID ; Exalenz Bioscience Ltd , Jerusalem , Israel ) was administered intragastrically and followed by a 4-hour continuous recording of expiratory (13)CO2 by the BreathID . Prokinetics were changed daily : ( 1 ) baseline ( no prokinetic ) , ( 2 ) intravenous ( IV ) metoclopramide ( 10 mg every 6 hours ) , ( 3 ) IV metoclopramide ( 10 mg every 6 hours ) and continuous low-dose erythromycin ( 10 mg/h ) , ( 4 ) IV continuous low-dose erythromycin alone ( 10 mg/h ) , and ( 5 ) IV bolus erythromycin ( 200 mg every 12 hours ) . Gastric-emptying rate was assessed by the percentage dose recovered (PDR)-change from time 0 of the recording in the ratio of (13)CO2/(12)CO2 in exhaled gases ( % /h ) . We used PDR peak values and time to peak ( minutes to reach PDR peak ) to express GER . RESULTS In the first 17 patients ( group A ) , baseline GER measurements preceded prokinetic therapy . In the subsequent 14 patients ( group B ) , 2 prokinetic regimens preceded baseline . No order-time effect was observed , justifying pooled analysis of all 31 patients . Combined metoclopramide-continuous low-dose erythromycin yielded significantly higher PDR peak and shorter time to peak vs baseline ( P = .0001 , P = .005 , respectively ) . The PDR peak was also significantly higher from baseline during continuous low-dose administration of erythromycin alone ( P = .004 ) . Metoclopramide alone did not improve GER significantly . CONCLUSIONS Combined metoclopramide-continuous low-dose erythromycin was found to be the best protocol in the current study to increase GER in ventilated patients . It should be tested as a first-line prokinetic therapy in ventilated patients with poor gastric emptying in further r and omized controlled studies . The breath-test device presented in this study can be a user-friendly and practical method to monitor GER , enabling individual tailoring of prokinetic therapy . Further studies to explore its utility are warranted BACKGROUND & AIMS Continuous pump feeding is often used to reduce aspiration risk in older patients on tube feeding , but its effectiveness in preventing aspiration pneumonia is unproven . A r and omized controlled trial was therefore performed to examine the effectiveness of continuous pump feeding in decreasing the incidence of pneumonia in tube-fed older hospital patients . METHODS One hundred and seventy eight elderly patients from three convalescence hospitals and one infirmary , on nasogastric tube feeding , were r and omly assigned to have intermittent bolus ( bolus ) or continuous pump ( pump ) feeding for 4weeks . The primary outcome was the incidence of pneumonia . The secondary outcome was mortality . RESULTS Eighty five subjects were r and omized into the pump group and 93 in the bolus group . The groups were comparable in age , nutritional and functional status , co-morbidities and history of pneumonia , except that there were more women in the pump group . Within 4weeks , 15 subjects ( 17.6 % ) in the pump group and 18 ( 19.4 % ) in the bolus group developed pneumonia . Seven subjects ( 8.2 % ) in pump group and 13 subjects ( 14.0 % ) in bolus group died . There was no significant difference in either pneumonia or death rates between the two groups . CONCLUSION Continuous pump feeding did not significantly affect the rates of pneumonia or mortality in tube-fed older hospital patients when compared with intermittent bolus feeding Objective To study the effects of pharmacologically increasing gastric pH on gastric colonization and the development of pneumonia in intubated critically ill patients . Design R and omized , controlled trial . Setting Medical ICU in a university hospital . Patients Thirty-four tracheotomized patients with tetanus . Interventions Sixteen patients received iv ranitidine to increase gastric pH > 4 ( ranitidine group ) , while 18 patients received no prophylaxis for upper gastrointestinal bleeding ( control group ) . Measurements and Main Results Mean gastric pH was higher in the ranitidine group ( median 4.7 , range 3.6 to 6.1 ) than in the control group ( median 2.1 , range 1.2 to 4.9 ; p < .05 ) . Gastric colonization occurred in 15 ( 94 % ) of 16 patients who received ranitidine , 2 days ( median ; range 1 to 5 ) after intubation ; gastric colonization also occurred in all control patients ( median 4 days , range 1 to 9 ; p < .05 ) . Pneumonia occurred in 13 ( 81 % ) of 16 patients who received ranitidine , 3 days ( median , range 1 to 5 ) after intubation and in nine ( 50 % ) of 18 control patients ( p < .01 ) 5 days after tracheal intubation ( median , range 3 to 14 ; p < .01 ) . Prior gastric colonization by the pathogen that caused pneumonia was demonstrable in nine ( 56 % ) of 16 patients who received ranitidine vs. eight ( 44 % ) of 18 control patients ( p > .05 ) . The risk for developing pneumonia in the ranitidine-treated group was highest in the first 4 days after tracheal intubation . There was no difference in the frequency of upper gastrointestinal hemorrhage in the two groups . Conclusions Pharmacologically increasing gastric pH increases the risk for developing pneumonia in intubated critically ill patients . The pneumonia occurs earlier than in untreated control patients . ( Crit Care Med 1992 ; 20:590–593 Objective : To determine whether metoclopramide prevents nosocomial pneumonia in intensive care unit ( ICU ) patients receiving enteral feeding by a nasogastric tube . Design : Prospect i ve , r and omized , controlled trial . Setting : ICU of a university hospital . Patients : A total of 305 consecutive patients requiring placement of a nasogastric tube for > 24 hrs . Interventions : Patients were r and omized to receive either 10 mg of metoclopramide or placebo at 8‐hr intervals through the nasogastric tube . Measurements and Main Results : A total of 174 patients received placebo and 131 received metoclopramide . Baseline characteristics in the two treatment groups were comparable . Of the 305 patients , 46 developed nosocomial pneumonia , which was 24 patients ( 13.7 % ) in the placebo group and 22 ( 16.8 % ) in the metoclopramide group ( p > .05 ) . Patients in the placebo group developed pneumonia earlier than patients receiving metoclopramide ( 4.46 ± 1.72 days [ mean ± SD[rsqb ] after ICU admission compared with 5.95 ± 1.78 days ; p = .006 ) . Subgroup analysis showed that metoclopramide did not reduce the frequency rate of pneumonia in patients with tracheal intubation ( 19 [ 25.3 % ] of 75 patients receiving metoclopramide vs. 21 [ 21.2 % ] of 99 patients receiving placebo ) or those receiving mechanical ventilation ( 17 [ 25.6 % ] of 58 patients receiving metoclopramide vs. 20 [ 29.3 % ] of 78 patients receiving placebo ) . The mortality rate also did not differ in the two treatments groups ( 56 % in the metoclopramide group vs. 53 % in the placebo group ; p > .05 ) . Conclusions : Although metoclopramide delayed the development of nosocomial pneumonia , it did not decrease its frequency rate and had no effect on the mortality rate in critically ill patients receiving nasogastric enteral feeding The aim of this study was to evaluate the effect of two body positions ( supine and semirecumbency ) on the dynamics of gastroesophageal reflux ( GER ) in 15 patients requiring mechanical ventilation and having a nasogastric tube in place . Sample s of gastric contents , pharyngeal and bronchial secretions , and blood were obtained at baseline and every hour during a period of 5 h after nasogastric tube isotopic instillation of 37 megabecquerels of Tc99 m . Radioactivity counting ( RAc ) was performed using a gamma counter with correction for decay . Irrespective of the body position , all patients showed at 3 , 4 , and 5 h after the isotope instillation a significant increase in RAc of the oropharyngeal contents ( p < 0.05 , each ) , indicating GER . Although RAc values in the pharynx were higher in supine from 1 through 4 h ( p < 0.05 ) , at the end of the study ( 5 h ) the values did not differ between each position . Likewise , the slopes of the regression lines of sequential oropharyngeal RAc values were not different between each position ( 0.39 + /- 0.09 versus 0.45 + /- 0.11 , respectively ) . In contrast , RAc values in bronchial secretions were higher at 5 h in the supine position compared with baseline ( p < 0.05 ) and to semirecumbency ( p < 0.01 ) . These results strongly support that GER in mechanically ventilated patients with a nasogastric tube is a feature occurring irrespective of body position . Semirecumbent position does not protect completely from GER and subsequently from oropharyngeal colonization from gastric origin Pneumonia is a prevalent cause of death in care home residents . Dysphagia is a significant risk factor of aspiration pneumonia . The purpose of the current study was to screen for risk of aspiration in care home residents in the Netherl and s and assess potential risk factors of aspiration . Five experienced speech- language therapists assessed 203 care home residents ( 115 primarily physically disabled , 88 primarily cognitively impaired ) 60 and older in the first week after admission to a care home . In 43 ( 21.2 % ) residents , speech- language therapists assessed risk of aspiration and found no significant difference between physically disabled ( 26.1 % ) and cognitively impaired ( 14.8 % ) residents . After multivariate logistic regression analysis , the final prediction model for risk of aspiration showed Parkinson 's disease as a significant factor ( odds ratio = 5.11 ; 95 % confidence interval [ 1.49 , 17.52 ] ) . The authors therefore conclude that risk of aspiration is a relevant care problem among Dutch care home residents and requires further assessment INTRODUCTION The use of procinéticos in the critical patient with nutrition enteral , they have as aim reduce the increase of the gastric residue ( RG ) . We evaluate his efficiency in the improvement of the intake enteral and on the reduction in the incident gastrointestinal complications ( CGI ) and pneumonia , in critical patients , with neurological injury Aims : To evaluate the effects in the administration metoclopramide ( MCG ) , during the first five days with enteral nutrition , versus control ( GC ) , on the volume of administered diet , gastrointestinal complications and the incidence of mechanical ventilation associated pneumonia ( NAVM ) , in neuro-critically patients ( NC ) of traumatic and vascular aetiology . Prospect i ve , closed-label , r and omized study performed in an intensive Care Unit . Methords : 150 adult neuro-critical patients ( NC ) were admitted of consecutive form and 109 were r and omly and two groups 58 MCG y 51 GC . The primary outcomes was the nutritional : the volume of administered diet ( VAD ) ; mean efficacious volume ( MEV ) measured in three consecutive periods of time ; the gastrointestinal complications ( GIC ) , and the rate of partial and definitive suspension of the diet . Infecction : incidence of ventilator associated pneumonia NAVM ; and of secondary outcomes were : the duration of mechanical ventilation , length of ICU and hospital stay , and incidence the serious sequelae , and 30 days mortality . RESULTS Differences were not observed in the severity variables between groups on admission . A significant increase was observed in the global values and in the first five days of ( p < 0.03 ) of the VEM in the group of MCG . The values of the global VDA and during three phases of study , the number CGI , the rate of partial and definitive suspensions of the diet , and number of NAVM , were similar in both not significant groups . Neither differences were observed in the overall analysis secondary variables . CONCLUSIONS The metoclopramida in the NC , it is not effective in the decrease of the CGI , in the doses and time of treatment reflected in the study |
10,338 | 28,236,011 | No major side effects have been described in those who used electrochemotherapy as a mono modality palliative treatment .
This systematic review shows how st and ardization of treatment is still pivotal to achieve a more homogeneous response rate in the approach to head and neck tumors . | Electroporation , also known as electrochemotherapy , combines an antineoplastic agent with electroporation , causing localized progressive necrosis in the treated area .
Today it is primarily used in the palliative treatment of cutaneous and subcutaneous metastases and has been found to be safe and efficacious in head and neck cancer recurrences .
Despite the steady increase in the number of published studies this treatment is not universally available and used systematic ally in head and neck carcinomas .
To shed light on its limitations and analyze treatment outcome we have , therefore , review ed all available literature regarding this topic . | Electrochemotherapy ( ECT ) is a new antitumor approach that combines systemic bleomycin ( BLM ) with electric pulses ( EP ) delivered locally at the tumor site . These EP permeabilize the cells in the tissue , allow BLM delivery inside the cells , and increase BLM cytotoxicity . As an extension of our initial Phase I trial on patients with head and neck squamous cell carcinoma ( HNSCC ) permeation nodules , we tested variations of ECT protocol to determine how to improve it OBJECTIVES To determine the safety and efficacy of electroporation with bleomycin in patients with advanced squamous cell carcinoma of the head and neck . METHODS Two open-label , multicenter , single-arm Phase II studies of intratumour electroporation therapy . Sixty-two patients with 86 squamous cell carcinoma tumours of the head and neck were enrolled . Twenty-five patients were treated with bleomycin alone . Fifty-four patients ( 17 initially treated with bleomycin alone ) were treated with electroporation and bleomycin therapy . Local tumour response was measured . RESULTS In the bleomycin alone group , one tumour showed a partial response and 36 tumours showed no response to treatment . In the bleomycin with electroporation groups , 17 tumours showed complete response , 22 tumours showed partial response and 30 failed to achieve more than a 50 % reduction in tumour size ( no response ) . Bleomycin with electroporation had a significantly ( p<0.001 ) greater number of patients showing a partial or complete response to the therapy when compared to bleomycin alone . Thirteen adverse events were reported which included five episodes of local bleeding , six local infections , one local tongue swelling and one cardiac arrhythmia . CONCLUSIONS Fifty-seven percent of squamous cell carcinomas of the head and neck demonstrated a partial or complete response to intratumour electroporation with bleomycin suggesting that further work investigating its use as a treatment for local control of these lesions should be pursued AIMS AND BACKGROUND Electrochemotherapy is a tumor ablation modality providing delivery into the cell interior of impermeant or poorly permeant chemotherapeutic drugs such as cisplatin and bleomycin . A locally applied electrical field enhances the membrane permeability allowing intracellular accumulation of the chemotherapeutic agent . The aim of the study was to evaluate the effectiveness of ECT for the treatment of a group of patients affected by recurrent of extended primary head and neck cancer and not suitable for st and ard therapeutic options . METHODS AND STUDY DESIGN From April 2009 to January 2011 , we treated with electrochemotherapy a total of 15 patients with head and neck cancers , 13 with squamous cell carcinoma , 1 with basaloid carcinoma and 1 with Merkel cell carcinoma . Electrical pulses were delivered to 33 lesions ( 3 primaries , 30 recurrences ) after an intravenous bolus injection of a dose of 15,000 IU/m2 of bleomycin . In 3 cases , the lesion treated was a pathologic lymph node . RESULTS Of the 31 lesions assessable for the study , 19 ( 61.5 % ) showed a complete response , 10 ( 32.5 % ) a partial response , 1 ( 3 % ) stable disease and 1 ( 3 % ) progression of the disease . The objective response 2 months after the procedure was 94 % . All the lesions that underwent complete regression were less than 3 cm in their maximum diameter . The 2 assessable cases of pathologic lymph nodes showed a partial or no response . After a follow-up of 2 to 20 months , 29 % of the patients were alive and free of disease , 50 % were alive with disease , 14 % died for disease and 7 % died for other causes . CONCLUSIONS Our study confirms the effectiveness of electrochemotherapy in the treatment or local control of recurrent or extended primary head and neck cancer in patients not suitable for st and ard therapeutic options Background . Electrochemotherapy is a new antitumor treatment consisting of electrical pulses administered to the tumor several minutes after intravenous injection of bleomycin . In mice , important antitumor effects were observed on subcutaneously transplanted tumors and on spontaneously occurring mammary carcinomas . Cures were obtained after one single treatment combining bleomycin and electric pulses . In humans , permeation nodules seemed an adequate oncologic situation to assay this new procedure . The authors report the first Phase I‐II trial of electrochemotherapy • Chemo‐electroporation therapy with bleomycin is a locoregional treatment modality for head and neck and skin cancer , with the potential to preserve function Many conventional chemotherapeutic drugs , as well as DNA for cancer gene therapy , require efficient access to the cells ' interior to be effective . The cell membrane is a formidable barrier to many of these drugs , including therapeutic DNA constructs . Electropermeabilization ( EP , often used synonymously with “ electroporation ” ) has become a useful method to temporarily increase the permeability of the cell membrane , allowing a broad variety of molecules efficient access to the cell interior . EP is achieved by the application of short electrical pulses of relatively high local field strength to the target tissue of choice . In cancer therapy , EP can be applied in vivo directly to the tumor to be treated , in order to enhance intracellular uptake of drugs or DNA . Alternatively , EP can be used to deliver DNA into cells of healthy tissue to achieve longer-lasting expression of cancer-suppressing genes . In addition , EP has been used in ex vivo therapeutic approaches for the transfection of a variety of cells in suspension . In this paper , we communicate results related to the development of a treatment for squamous cell carcinomas of the head and neck , using electropermeabilization to deliver the drug bleomycin in vivo directly into the tumor cells . This drug , which is not particularly effective as a conventional therapeutic , becomes highly potent when the intracellular concentration is enhanced by EP treatment . In animal model experiments we found a drug dose of 1 U/cm3 tumor tissue ( delivered in 0.25 mL of an aqueous solution/cm3 tumor tissue ) and an electrical field strength of 750 V/cm or higher to be optimal for the treatment of human squamous cell tumors grown subcutaneously in mice . Within 24–48 hours , the majority of tumor cells are rapidly destroyed by this bleomycin-electroporation therapy ( B-EPT ) . This raises the concern that healthy tissue may be similarly affected . In studies with large animals we showed that normal muscle and skin tissue , normal tissue surrounding major blood vessels and nerves , as well as healthy blood vessels and nerves themselves , are much less affected than tumor tissue . Normal tissues did show acute , focal , and transitory effects after treatment , but these effects are relatively minor under st and ard treatment conditions . The severity of these effects increases with the number of electric pulse cycles and applied voltage . The observed histological changes resolved 20 to 40 days after treatment or sooner , even after excessive EP treatment . Thus , B-EPT is distinct from other ablative therapies , such as thermal , cryo , or photodynamic ablation , which equally affect healthy and tumor tissue . In comparison to surgical or radiation therapy , B-EPT also has potential as a tissue-sparing and function-preserving therapy . In clinical studies with over 50 late stage head and neck cancer patients , objective tumor response rates of 55–58 % , and complete tumor response rates of 19–30 % have been achieved OBJECTIVES Electroporation therapy with intralesional bleomycin ( EPT ) is a novel , technically simple outpatient technique in which high-voltage electric impulses delivered into a neoplasm transiently increase cell membrane permeability to large molecules , including cytotoxic agents , causing localized progressive necrosis . Unlike many laser ablation methods , EPT can treat bulky tumors ( > 2 cm ) with complete penetration . Our recent publication confirms an excellent response rate in the use of EPT in a clinical trial . STUDY DESIGN , PATIENTS , AND METHODS Following our initial prospect i ve study report in 1998 , we have followed our entire initial cohort ( 10 patients ) of patients with head and neck cancer beyond 24-months follow-up . Additionally , we have used this approach to treat four additional patients ( total : 9 males/5 females ) with upper aerodigestive tract squamous cell carcinoma , including three with internal carotid artery ( ICA ) involvement up to or within the skull base . Two patients underwent preoperative balloon test occlusion with cerebral perfusion studies followed by carotid embolization . EPT was then done safely at least 2 weeks later to avoid the temporary hypercoagulable state . RESULTS Within the overall cohort ( 14 patients ) 6 patients had a complete response , 6 had a partial response , and 2 did not respond ( overall 85.7 % response rate ) . Both patients with ICA involvement had a partial or complete response to treatment ; neither patient had a hemorrhagic or neurologic complication . Overall , 13 of the 14 patients were treated for persistent or recurrent head and neck cancer . Two of the four patients with early recurrent stage tumors had no evidence of recurrence after EPT with an average follow-up of 31.5 months . The overall early stage tumor group had four complete responders out of five ( 80 % ) . On the contrary , only 2 of 9 patients with advanced recurrent stage tumors were disease-free at 18 months . Morbidity was low for early stage tumors , but higher for advanced tumors with complications , including poor wound healing , dysphagia , and osteomyelitis . There were no treatment-related deaths . CONCLUSION We found EPT to be safe and efficacious in patients with head and neck cancer , even with internal carotid artery involvement . Patients with early stage recurrences have the potential for prolonged survival beyond 2 years without the morbidity of surgery and radiation or toxicity of systemic chemotherapy . Because of its superb access qualities even for bulky tumors , EPT is a potential method of delivery for other tumoricidal agents such as in genetic-altering schemes |
10,339 | 26,920,369 | The pain assessment s , PAINAD and PACSLAC had the strongest psychometric evidence .
The oral health , discomfort , and three psychological wellbeing measures were vali date d in this setting but require further psychometric evaluation .
Depression measures were poor at detecting depression in this population .
Conclusions Measures for pain are best developed for this population and setting . | Background High symptom burden is common in long-term care residents with dementia and results in distress and behavioral challenges if undetected .
Physicians may have limited time to regularly examine all residents , particularly those unable to self-report , and may rely on reports from caregivers who are frequently in a good position to detect symptoms quickly .
We aim ed to identify proxy-completed assessment measures of symptoms experienced by people with dementia , and critically appraise the psychometric properties and applicability for use in long-term care setting s by caregivers . | The purpose of this study was to examine the psychometric properties ( test-retest and interrater reliability , criterion concurrent validity ) of 3 verbal pain- assessment tools ( Faces Pain Scale , Numerical Rating Scale , Present Pain Intensity Scale ) and a behavioural pain- assessment scale for use with an elderly population . The study used a repeated- measures design to examine the reliability and validity of the tools across 4 groups of participants with varying levels of cognitive impairment using a non-r and om stratified sample of 130 elderly long-term-care residents . The findings support the test-retest and interrater reliability of the behavioural pain- assessment tool across all levels of cognitive impairment , whereas the same measures of reliability for the verbal-report tools decreased with increasing cognitive impairment ; however , the majority of elderly with mild to moderate cognitive impairment were able to complete at least 1 of these tools . The findings are discussed in relation to their clinical and research implication BACKGROUND Nursing homes ( NHs ) are less well studied than hospices or hospitals as a setting for terminal care . For more targeted palliative care , more information is needed about the patient characteristics , symptoms , direct causes and underlying diseases , and incidence of terminally ill NH patients . These aspects are examined in this study . METHODS Prospect i ve observational cohort study in 16 NHs representative of the Netherl and s. All long-term care patients assessed by an NH physician to have a life expectancy of 6 weeks or less were enrolled in our study . RESULTS The terminal disease phase was marked with symptoms of low fluid and food intake , general weakness , and respiratory problems or dyspnea . Direct causes of these conditions were diseases of the respiratory system ( mainly pneumonia ) and general disorders ( eg , cachexia ) . The 2 main underlying diseases of the terminal phase were mental and behavioral disorders and diseases of the circulatory system . Cancer was the underlying disease in only 12 % of the patients . Patients with cancer showed a different pattern of symptoms than those without cancer . Per 100 beds per year , 34 NH patients entered the terminal phase . Most patients ( 82.9 % ) died within 7 days of inclusion . CONCLUSIONS For patients without cancer in Dutch NHs , the terminal disease phase is difficult to predict , and once diagnosed , patient survival time is short . A better identification of the symptom burden might improve the prognostication of life expectancy in elderly patients The aim of this study was to assess the Palliative care Outcome Scale ( POS ) for terminally ill nursing home ( NH ) patients in the Netherl and s. Methods : A prospect i ve observational study of patients with a life-expectancy of six weeks or less in 16 Dutch NHs . NH staff rated the patient characteristics and measured palliative care with the POS , including items on physical , psychosocial , informational , spiritual and practical aspects . Results : POS nonscores ( not applicable ; unknown ) were mainly found in the psychosocial and spiritual domains , particularly in patients with dementia . Mean scores for non-demented patients and patients with dementia were favourable for the majority of the POS items . Conclusion : According to the NH staff , fairly good quality care was provided , but the psychosocial and spiritual aspects of care need to be addressed more in the last days of the dying NH patient 's life . The results indicate that the POS is an appropriate instrument to assess not only cancer patients , but also non-cancer and ( moderately ) severely demented patients Pain is a common problem for many older adults , with up to 50 % of community-dwelling and 70 % to 80 % of nursing home residents experiencing pain regularly . Effective pain management requires thorough assessment , appropriate intervention , and systematic re assessment . Pain assessment , however , is complicated by dementia , which impairs memory , reasoning , recognition , and communication , and affects elders ' ability to verbally report pain . As such , observational measures are needed to assess pain in this vulnerable population . The Non-communicative Patient 's Pain Assessment Instrument ( NOPPAIN ) was developed for this purpose , but more validation of this measure is needed . Thus , the purpose of this study was to ( 1 ) evaluate reliability of the NOPPAIN tool when used by nurses and to ( 2 ) compare NOPPAIN ratings with self-report and other well-established behavioral rating procedures . Forty participants ( 20 cognitively intact and 20 impaired ) were r and omly selected for this study from a larger sample . In the parent study , participants were asked to perform everyday activities ( i.e. , sit , st and , walk in place , transfer in and out of bed ) while being videotaped . The tapes , all previously scored using microanalytic observational coding , were rated again by naïve raters using the NOPPAIN measure . Results indicated ( 1 ) high inter- and intrarater reliability of the NOPPAIN and ( 2 ) significant correlations of the NOPPAIN with self-reported pain and detailed behavioral coding . Findings support the reliability and validity of the NOPPAIN measurement tool and suggest this easy-to-use tool may be adequate for measuring pain indicators in older adults The Neuropsychiatric Inventory ( NPI ) is a vali date d clinical instrument for evaluating psychopathology in dementia . The authors developed a brief question naire form of the NPI ( NPI-Q ) , intended for use in routine clinical practice , and cross-vali date d it with the NPI in 60 Alzheimer 's patients . Test-retest reliability of the NPI-Q was acceptable . The prevalence of analogous symptoms reported on the NPI and NPI-Q differed on average by 5 % ; moderate or severe symptom ratings differed by less than 2 % . The NPI-Q provides a brief , reliable , informant-based assessment of neuropsychiatric symptoms and associated caregiver distress that may be suitable for use in general clinical practice & NA ; With the increasing numbers of older adults in our population , nurses are reexamining all aspects of nursing care in order to best meet the needs of these individuals . Normal age changes , the impact of decades of environmental challenges , successful adaptations , acute illnesses , trauma and chronic illnesses combine to create a challenge for accurate and effective assessment of elderly patients . The nurse finds her assessment skills challenged with increasing frequency by the elderly patient who is also acutely confused and experiencing discomfort . The purpose of this study was to explore the clinical utility , validity and reliability of four different approaches to nursing assessment of discomfort with this particularly vulnerable group of elders BACKGROUND depression is common but under-diagnosed in nursing-home residents . There is a need for a st and ardized screening instrument which incorporates daily observations of nursing-home staff . AIM to develop and vali date a screening instrument for depression using items from the Minimum Data Set of the Resident Assessment Instrument . METHODS we conducted semi-structured interviews with 108 residents from two nursing homes to obtain depression ratings using the 17-item Hamilton Depression Rating Scale and the Cornell Scale for Depression in Dementia . Nursing staff completed Minimum Data Set assessment s. In a r and omly assigned derivation sample ( n = 81 ) , we identified Minimum Data Set mood items that were correlated ( P < 0.05 ) with Hamilton and Cornell ratings . These items were factored using an oblique rotation to yield five conceptually distinct factors . Using linear regression , each set of factored items was regressed against Hamilton and Cornell ratings to identify a core set of seven Minimum Data Set mood items which comprise the Minimum Data Set Depression Rating Scale . We then tested the performance of the Minimum Data Set Depression Rating Scale against accepted cut-offs and psychiatric diagnoses . RESULTS a cutpoint score of 3 on the Minimum Data Set Depression Rating Scale maximized sensitivity ( 94 % for Hamilton , 78 % for Cornell ) with minimal loss of specificity ( 72 % for Hamilton , 77 % for Cornell ) when tested against cut-offs for mild to moderate depression in the derivation sample . Results were similar in the validation sample . When tested against diagnoses of major or non-major depression in a subset of 82 subjects , sensitivity was 91 % and specificity was 69 % . Performance compared favourably with the 15-item Geriatric Depression Scale . CONCLUSION items from the Minimum Data Set can be organized to screen for depression in nursing-home residents . Further testing of the instrument is now needed Purpose Quality of care for long-term care ( LTC ) residents with dementia at the end-of-life is often evaluated using st and ardized instruments that were not developed for or thoroughly tested in this population . Given the importance of using appropriate instruments to evaluate the quality of care ( QOC ) and quality of dying ( QOD ) in LTC , we compared the validity and reliability of ten available instruments commonly used for these purpose s. Methods We performed prospect i ve observations and retrospective interviews and surveys of family ( n = 70 ) and professionals ( n = 103 ) of LTC decedents with dementia in the Netherl and s. Results Instruments within the constructs QOC and QOD were highly correlated , and showed moderate to high correlation with overall assessment s of QOC and QOD . Prospect i ve and retrospective ratings using the same instruments differed little . Concordance between family and professional scores was low . Cronbach ’s alpha was mostly adequate . The EOLD – CAD showed good fit with pre-assumed factor structures . The EOLD – SWC and FPCS appear most valid and reliable for measuring QOC , and the EOLD – CAD and MSSE for measuring QOD . The POS performed worst in this population . Conclusions Our comparative study of psychometric properties of instruments allows for informed selection of QOC and QOD measures for LTC residents with dementia Objective To determine whether a systematic approach to the treatment of pain can reduce agitation in people with moderate to severe dementia living in nursing homes . Design Cluster r and omised controlled trial . Setting 60 clusters ( single independent nursing home units ) in 18 nursing homes within five municipalities of western Norway . Participants 352 residents with moderate to severe dementia and clinical ly significant behavioural disturbances r and omised to a stepwise protocol for the treatment of pain for eight weeks with additional follow-up four weeks after the end of treatment ( 33 clusters ; n=175 ) or to usual treatment ( control , 27 clusters ; n=177 ) . Intervention Participants in the intervention group received individual daily treatment of pain for eight weeks according to the stepwise protocol , with paracetamol ( acetaminophen ) , morphine , buprenorphine transdermal patch , or pregabaline . The control group received usual treatment and care . Main outcome measures Primary outcome measure was agitation ( scores on Cohen-Mansfield agitation inventory ) . Secondary outcome measures were aggression ( scores on neuropsychiatric inventory-nursing home version ) , pain ( scores on mobilisation-observation-behaviour-intensity-dementia-2 ) , activities of daily living , and cognition ( mini-mental state examination ) . Results Agitation was significantly reduced in the intervention group compared with control group after eight weeks ( repeated measures analysis of covariance adjusting for baseline score , P<0.001 ) : the average reduction in scores for agitation was 17 % ( treatment effect estimate −7.0 , 95 % confidence interval −3.7 to −10.3 ) . Treatment of pain was also significantly beneficial for the overall severity of neuropsychiatric symptoms ( −9.0 , −5.5 to −12.6 ) and pain ( −1.3 , −0.8 to −1.7 ) , but the groups did not differ significantly for activities of daily living or cognition . Conclusion A systematic approach to the management of pain significantly reduced agitation in residents of nursing homes with moderate to severe dementia . Effective management of pain can play an important part in the treatment of agitation and could reduce the number of unnecessary prescriptions for psychotropic drugs in this population . Trial registration Clinical Trials.gov NCT01021696 and Norwegian Medicines Agency EudraCTnr 2008 - 007490 - 20 A method for assessing affect states among older people with Alzheimer 's disease was developed for use in a study design ed to evaluate a special care unit for such residents of a nursing home . The 6-item Philadelphia Geriatric Center Affect Rating Scale was design ed for the use of research and other staff in assessing positive affect ( pleasure , interest , contentment ) and negative affect ( sadness , worry/anxiety , and anger ) by direct observation of facial expression , body movement , and other cues that do not depend on self-report , among 253 demented and 43 nondemented residents . Each affect scale was highly reliable , expressed in estimated portions of a 10-minute observation period when the affect expression occurred . Validity estimates were affirmative in showing discriminant correlations between the positive states and various independent measures of social and other outwardly engaged behavior and between negative states and other measures of depression , anger , anxiety , and withdrawal . Limited support for the two-factor dimensionality of the affect ratings was obtained , although positive and negative affect were correlated , rather than independent . Some hope is offered that the preference and aversions of Alzheimer patients may be better understood by observations of their emotional behaviors and that such methods may lead to a better ability to judge institutional quality OBJECTIVES To describe the end-of-life symptoms of nursing home ( NH ) and residential care/assisted living ( RC/AL ) residents , compare staff and family symptom ratings , and compare how staff assess pain and dyspnea for cognitively impaired and cognitively intact residents . DESIGN After-death interviews . SETTING Stratified r and om sample of 230 long-term care facilities in four states . PARTICIPANTS Staff ( n=674 ) and family ( n=446 ) caregivers for dying residents . MEASUREMENTS Interview items measured frequency and severity of physical symptoms , effectiveness of treatment , recommendations to improve care , and staff report of assessment . RESULTS Decedents ' median age was 85 , 89 % were white , and 77 % were cognitively impaired . In their last month of life , 47 % had pain , 48 % dyspnea , 90 % problems with cleanliness , and 72 % symptoms affecting intake . Problems with cleanliness , intake , and overall symptom burden were worse for decedents in NHs than for those in RC/AL . Treatment for pain and dyspnea was rated very effective for only half of decedents . For a subset of residents with both staff and family interviews ( n=331 ) , overall ratings of care were similar , although agreement in paired analyses was modest ( kappa=-0.043 - 0.425 ) . Staff relied on nonverbal expressions to assess dyspnea but not pain . Both groups of caregivers recommended improved application of treatment and increased staffing to improve care . CONCLUSION In NHs and RC/AL , dying residents have high rates of physical symptoms and need for more-effective palliation of symptoms near the end of life OBJECTIVES To test the feasibility and validity of the Patient Health Question naire-9 item interview ( PHQ-9 ) and the newly developed Patient Health Question naire Observational Version ( PHQ-9 OV ) for screening for mood disorder in nursing home population s. METHODS The PHQ-9 was tested as part of the national Minimum Data Set 3.0 ( MDS 3.0 ) evaluation study among 3822 residents scheduled for MDS 2.0 assessment s. Residents from 71 community nursing homes ( NHs ) in eight states were r and omly included in a feasibility sample ( n = 3258 ) and a validation sample ( n = 418 ) . Each resident 's ability to communicate determined whether the PHQ-9 interview or the PHQ-9 OV was initially attempted . In the validation sample , trained research nurses administered the instruments . For residents in the validation sample without severe cognitive impairment ( 3 MS ≥30 ) agreement between PHQ-9 and the modified Schedule for Affective Disorders and Schizophrenia ( m-SADS ) was measured with weighted kappas ( κ ) . For residents with severe cognitive impairment ( 3MS < 30 ) , agreement between PHQ-9 interview or PHQ-9 OV and the Cornell Scale for Depression in Dementia ( Cornell Scale ) was measured using correlation coefficients . Staff impressions were obtained from an anonymous survey mailed to all MDS assessors . RESULTS The PHQ-9 was completed in 86 % of the 3258 residents in the feasibility sample . In the validation sample , the agreement between PHQ-9 and m-SADS was very good ( weighted κ = 0.69 , 95 % CI = 0.61 - 0.76 ) , whereas agreement between MDS 2.0 and m-SADS was poor ( weighted κ = 0.15 , 95 % CI = 0.06 - 0.25 ) . Likewise , in residents with severe cognitive impairment , PHQ correlations with the criterion st and ard Cornell Scale were superior to the MDS 2.0 for both the PHQ-9 ( 0.63 vs 0.34 ) and the PHQ-9 OV ( 0.84 vs 0.28 ) . Eighty-six percent of survey respondents reported that the PHQ-9 provided new insight into residents ' mood . The average time for completing the PHQ-9 interview was 4 minutes . DISCUSSION Compared with the MDS 2.0 observational items , the PHQ-9 interview had greater agreement with criterion st and ard diagnostic assessment s. For residents who could not complete the interview , the PHQ-9 OV also had greater agreement with a criterion measure for depression than did the MDS 2.0 observational items . Moreover , the majority of NH residents were able to complete the PHQ-9 , and most surveyed staff reported improved assessment s with the new approach BACKGROUND The observation scale PAINAD ( pain assessment in advanced dementia ) is composed of five behavioral categories : breathing , vocalization , facial expression , body language , and consolability . The present study investigates the construct validity of the German version . PATIENTS AND METHODS We conducted a prospect i ve one-dimensional observation study with repeated measurements ( t(1)=pretreatment , t(2)=2 h posttreatment , t(3)=24 h posttreatment ) . The sample consisted of 12 verbally noncommunicative demented in patients with severe comorbidity treated in three geriatric clinics . Their age was M=84.3 years ( SD=4.4 ) on the average . Ten of them were female . Inclusion criteria were pain-related physical illness and observed pain behavior . Every patient was treated with analgesics after t(1 ) . After t(2 ) the medication was discontinued in five patients until t(3 ) . Nurses documented the PAINAD scores after an observation period of 2 min during routine care . RESULTS Pain behavior at t(2 ) diminished considerably displaying a large effect size . Scores continued to be low at t(3 ) only in the sample with continued medication . Scores in the other part of the sample returned to initial values . CONCLUSION The data demonstrate that pain medication strongly impacts the pain behavior of demented patients . The outcome supports the assumption that PAINAD really measures pain OBJECTIVES : To develop an outcome measure for patients with advanced cancer and their families which would cover more than either physical symptoms or quality of life related questions . To vali date the measure in various specialist and non-specialist palliative care setting s throughout the UK . DESIGN : A systematic literature review of measures appropriate for use in palliative care setting s was conducted . In conjunction with a multidisciplinary project advisory group , questions were chosen for inclusion into the scale based on whether they measured aspects of physical , psychological , or spiritual domains pertinent to palliative care , and whether similar items had shown to be valid as part of another measure . A staff completed version was developed to facilitate data collection on all patients throughout their care , and a patient completed version was design ed to enable the patient to contribute to the assessment of their outcomes when possible . A full validation study was conducted to evaluate construct validity , internal consistency , responsiveness to change over time , and test-retest reliability . Assessment s were timed . SETTING : Eight centres in Engl and and Scotl and providing palliative care , including inpatient care , outpatient care , day care , home care , and primary care . PATIENTS : A total of 450 patients entered care during the study period . Staff collected data routinely on patients in care long enough to be assessed ( n = 337 ) . Of these , 262 were eligible for patient participation ; 148 ( 33 % ) went on to complete a question naire . MAIN MEASURES : The Palliative Care Outcome Scale ( POS ) , the European Organisation for Research on Cancer Treatment , and the Support Team Assessment Schedule . RESULTS : The POS consists of two almost identical measures , one of which is completed by staff , the other by patients . Agreement between staff and patient ratings was found to be acceptable for eight out of 10 items at the first assessment . The measure demonstrated construct validity ( Spearman rho = 0.43 to 0.80 ) . Test/re-test reliability was acceptable for seven items . Internal consistency was good ( Cronbach 's alpha = 0.65 ( patients ) , 0.70 ( staff ) ) . Change over time was shown , but did not reach statistical significance . The question naire did not take more than 10 minutes to complete by staff or patients . CONCLUSION : The POS has acceptable validity and reliability . It can be used to assess prospect ively palliative care for patients with advanced cancer The Assessment of Discomfort in Dementia ( ADD ) Protocol was developed to improve recognition and treatment of physical pain and affective discomfort in people with dementia who are no longer able to clearly or consistently report on their internal states . The purpose of this study was to describe use of each step of the ADD protocol with 143 residents of long-term care facilities . Of the subjects who received nonpharmacological comfort interventions , 37 % showed improved symptoms . Of the 91 protocol s in which an analgesic was administered , 83.5 % showed improved symptoms . People who complained verbally received considerably more analgesics and other comfort interventions . Limitations inherent in this descriptive exploratory study do not permit conclusions regarding the effectiveness of the ADD protocol . Research with a control group , r and om assignment , and objective measures of discomfort level is planned OBJECTIVE To examine and compare the psychometric properties of two common observational pain assessment tools used in persons with dementia . DESIGN In a cross-sectional descriptive study nursing home ( NH ) residents were videotaped at rest and during a structured movement procedure . Following one training session and one practice session , two trained graduate nursing research assistants independently scored the tapes using the two pain observation tools . SETTING Fourteen NHs in Western Washington State participating in a r and omized controlled trial of an intervention to enhance pain assessment and management . PARTICIPANTS Sixty participants with moderate to severe pain were identified by nursing staff or chosen based on the pain items from the most recent Minimum Data Set assessment . MEASURES Checklist of Nonverbal Pain Indicators ( CNPI ) and the Pain Assessment in Advanced Dementia ( PAINAD ) , demographic and pain-related data ( Minimum Data Set ) , nursing assistant reports of participants ' usual pain intensity , and Pittsburgh Agitation Scale . RESULTS Internal consistency for both tools was good except for the CNPI at rest for one rater . Inter-rater reliability for pain presence was fair ( K = 0.25 for CNPI with movement ; K = 0.31 for PAINAD at rest ) to moderate ( K = 0.43 for CNPI at rest ; K = 0.54 for PAINAD with movement ) . There were significant differences in mean CNPI and PAINAD scores at rest and during movement , providing support for construct validity . However , both tools demonstrated marked floor effects , particularly when participants were at rest . CONCLUSIONS Despite earlier studies supporting the reliability and validity of the CNPI and the PAINAD , findings from the current study indicate that these measures warrant further study with clinical users , should be used cautiously both in research and clinical setting s and only as part of a comprehensive approach to pain assessment OBJECTIVE To describe the last year of life of people with dementia , their symptoms , care needs , use of and satisfaction with health services and the bereavement state of the respondent . METHODS The study is drawn from the Regional Study of Care for the Dying , a retrospective sample survey of the carers , family members or others who knew about the last year of life of a r and om sample of people age 15 and over dying in the last quarter of 1990 . The sample s were drawn in 20 English health districts which , although self-selected , were nationally representative . There was a total of 3696 patients ( response rate of 69 % ) dying from all causes . Within this sample , 170 dementia patients were identified and compared with 1513 cancer patients . RESULTS The symptoms most commonly reported in the last year were mental confusion ( 83 % ) , urinary incontinence ( 72 % ) , pain ( 64 % ) , low mood ( 61 % ) , constipation ( 59 % ) and loss of appetite ( 57 % ) . Dementia patients saw their GP less often than cancer patients and their respondents rated GP assistance less highly . Dementia patients needed more help at home compared with cancer patients , and received more social services ; 78 % of respondents for dementia patients and 64 % for cancer said they had come to terms with the patient 's death . CONCLUSION Patients dying from dementia have symptoms and health care needs comparable with cancer patients . Greater attention should be given to these needs OBJECTIVES To establish the reliability and validity of a measure to assess pain in individuals with advanced dementia . DESIGN Sixty-five residents of long-term care facilities were assessed using a new rating tool , the Pain Assessment for the Dementing Elderly ( PADE ) , in two separate studies : ( 1 ) Residents were assessed simultaneously by two different raters , at Time 1 and 2 , to establish interrater reliability , stability , and internal consistency . ( 2 ) Validity was established by assessing the correlation between an agitation scale and the PADE ; by comparing groups with pain as a significant clinical factor ( as assessed by an independent rater ) versus not a significant factor , and by assessing individuals receiving versus not receiving psychoactive medications . SETTING Four different long-term care facilities , three skilled nursing facilities , and a locked dementia assisted-living facility . PARTICIPANTS Twenty-five residents of long-term care facilities with advanced levels of dementia in Study 1 , and 40 residents with similar level of dementia in Study 2 ; 42 % of the total sample were rated as having significant painful conditions . MEASUREMENTS For Study 1 , the PADE was administered ; for Study 2 , the PADE and the Cohen-Mansfield Agitation Inventory ( CMAI ) were administered . RESULTS Reliability coefficients were adequate ( interrater = 0.54 - 0.95 ; stability = 0.70 - 0.98 ; and internal consistency = 0.24 - 0.88 ) . Validity coefficients were likewise encouraging , with the PADE demonstrating the expected relationship with a measure of agitation . The PADE also differentiated between groups that were independently judged to suffer clinical ly problematic pain versus those who were not . CONCLUSION The PADE is a reliable and valid tool to assess pain in dementing elderly residents of long-term care facilities One hundred ninety-four patients undergoing comprehensive geriatric assessment completed the Geriatric Depression Scale ( GDS ) , and their collateral source ( CS ) completed a CS version of the GDS ( CS-GDS ) . The results were compared with the blind , prospect i ve diagnoses made by geriatric psychiatrists . The CSs reported the presence of 28 of 30 symptoms significantly more often than the patients . Receiver operating characteristic curve analyses showed good agreement among the clinical diagnoses and both the patient-completed GDS and the CS-completed CS-GDS . At cutoff scores used in prior studies of the GDS , the CS-GDS had limited specificity and poor positive predictive value |
10,340 | 28,456,764 | Prevalence of MRI findings was high in symptomatic and asymptomatic population . | Background Patellofemoral osteoarthritis ( PF OA ) is more prevalent than previously thought and contributes to patient ’s suffering from knee OA .
Synthesis of prevalence data can provide estimates of the burden of PF OA . | Objective : To evaluate whether patient characteristics and /or radiographic disease patterns predict symptomatic response to treatment with glucosamine in osteoarthritis ( OA ) of the knee . Design : Exploratory prospect i ve correlational study . Setting : Institutional . Patients : 39 participants with chronic knee pain from the local community . Interventions : Glucosamine sulphate ( 1.5 g/day ) for 12 weeks . Main outcome measures : Pain and physical function were assessed with visual analogue scales ( VASs ) and participant-perceived global change scores ( GCSs ) . Regression modelling evaluated the relationship between treatment outcome and age , body mass index ( BMI ) , pain and function self-efficacy and presence/absence of osteophytes in the medial and lateral tibiofemoral joint ( TFJ ) and patellofemoral joint ( PFJ ) compartments . Results : 13 ( 33 % ) participants were men . The mean ( SD ) age and BMI were 53.6 ( 13.1 ) years and 27.9 ( 4.6 ) kg/m2 , respectively . 13 ( 33 % ) , 19 ( 49 % ) and 24 ( 62 % ) participants had medial TFJ , lateral TFJ and PFJ osteophytes , respectively . Glucosamine significantly improved pain ( mean change on VAS = −1.4 , 95 % CI −0.6 to −2.2 ; p = 0.002 ) and activity restriction ( −1.9 , 95 % CI −1.0 to −2.8 ; p<0.001 ) . At 12 weeks , 30 ( 77 % ) and 27 ( 69 % ) participants reported improvement in pain and physical function , respectively . Regression modelling showed that no evaluated variables predicted change in pain on VAS . Decreased function self-efficacy , presence of PFJ osteophytes and absence of medial TFJ osteophytes predicted functional improvement on VAS . BMI , pain self-efficacy and function self-efficacy predicted improvement in pain by GCS . Conclusions : Although glucosamine significantly improved symptoms , most of the variance in outcome at 12 weeks was unexplained by the predictors evaluated . However , glucosamine may be more effective at improving symptoms in patients with knee OA who have a lower BMI , PFJ osteophytes and lower functional self-efficacy OBJECTIVE To determine the effect of quadriceps strength in individuals with knee osteoarthritis ( OA ) on loss of cartilage at the tibiofemoral and patellofemoral joints ( assessed by magnetic resonance imaging [ MRI ] ) and on knee pain and function . METHODS We studied 265 subjects ( 154 men and 111 women , mean+/-SD age 67+/-9 years ) who met the American College of Rheumatology criteria for symptomatic knee OA and who were participating in a prospect i ve , 30-month natural history study of knee OA . Quadriceps strength was measured at baseline , isokinetically , during concentric knee extension . MRI of the knee at baseline and at 15 and 30 months was used to assess cartilage loss at the tibiofemoral and patellofemoral joints , with medial and lateral compartments assessed separately . At baseline and at followup visits , knee pain was assessed using a visual analog scale , and physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index . RESULTS There was no association between quadriceps strength and cartilage loss at the tibiofemoral joint . Results were similar in malaligned knees . However , greater quadriceps strength was protective against cartilage loss at the lateral compartment of the patellofemoral joint ( for highest versus lowest tertile of strength , odds ratio 0.4 [ 95 % confidence interval 0.2 , 0.9 ] ) . Those with greater quadriceps strength had less knee pain and better physical function over followup ( P<0.001 ) . CONCLUSION Greater quadriceps strength had no influence on cartilage loss at the tibiofemoral joint , including in malaligned knees . We report for the first time that greater quadriceps strength protected against cartilage loss at the lateral compartment of the patellofemoral joint , a finding that requires confirmation . Subjects with greater quadriceps strength also had less knee pain and better physical function over followup Background A recent study of adults aged ≥50 years reporting knee pain found an excess of radiographic knee osteoarthritis ( knee ROA ) in symptomatic males compared to females . This was independent of age , BMI and other clinical signs and symptoms . Since this finding contradicts many previous studies , our objective was to explore four possible explanations for this gender difference : X-ray views , selection , occupation and non-articular conditions . Methods A community-based prospect i ve study . 819 adults aged ≥50 years reporting knee pain in the previous 12 months were recruited by postal question naires to a research clinic involving plain radiography ( weight-bearing posteroanterior semiflexed , supine skyline and lateral views ) , clinical interview and physical examination . Any knee ROA , ROA severity , tibiofemoral joint osteoarthritis ( TJOA ) and patellofemoral joint osteoarthritis ( PJOA ) were defined using all three radiographic views . Occupational class was derived from current or last job title . Proportions of each gender with symptomatic knee ROA were expressed as percentages , stratified by age ; differences between genders were expressed as percentage differences with 95 % confidence intervals . Results 745 symptomatic participants were eligible and had complete X-ray data . Males had a higher occurrence ( 77 % ) of any knee ROA than females ( 61 % ) . In 50–64 year olds , the excess in men was mild knee OA ( particularly PJOA ) ; in ≥65 year olds , the excess was both mild and moderate/severe knee OA ( particularly combined TJOA/PJOA ) . This male excess persisted when using the posteroanterior view only ( 64 % vs. 52 % ) . The lowest level of participation in the clinic was symptomatic females aged 65 + . Within each occupational class there were more males with symptomatic knee ROA than females . In those aged 50–64 years , non-articular conditions were equally common in both genders although , in those aged 65 + , they occurred more frequently in symptomatic females ( 41 % ) than males ( 31 % ) . Conclusion The excess of knee ROA among symptomatic males in this study seems unlikely to be attributable to the use of comprehensive X-ray views . Although prior occupational exposures and the presence of non-articular conditions can not be fully excluded , selective non-participation bias seems the most likely explanation . This has implication s for future study design Objective Braces used to treat ( PF ) osteoarthritis ( OA ) may reduce contact stress across the PF joint . We hypothesised that in PF OA , braces would decrease knee pain and shrink PF bone marrow lesions ( BMLs ) . Methods Eligible subjects had painful PF OA . Subjects were r and omly allocated to brace or no brace for 6 weeks . Knee MRIs were acquired at baseline and 6 weeks . We measured BMLs on post-contrast fat suppressed sagittal and proton density weighted axial images . The primary symptom outcome was change in pain at 6 weeks during a preselected painful activity , and the primary structural outcome was BML volume change in the PF joint . Analyses used multiple linear regression . Results We r and omised 126 subjects aged 40–70 years ( mean age 55.5 years ; 72 females ( 57.1 % ) ) . Mean nominated visual analogue scale ( 0–10 cm ) pain score at baseline was 6.5 cm . 94 knees ( 75 % ) had PF BMLs at baseline . Subjects wore the brace for a mean of 7.4 h/day . 6 subjects withdrew during the trial . After accounting for baseline values , the brace group had lower knee pain than the control group at 6 weeks ( difference between groups −1.3 cm , 95 % CI −2.0 to −0.7 ; p<0.001 ) and reduced PF BML volume ( difference −490.6 mm3 , 95 % CI −929.5 to −51.7 ; p=0.03 ) but not tibiofemoral volume ( difference −53.9 mm3 , 95 % CI −625.9 to 518.2 ; p=0.85 ) . Conclusions A PF brace reduces BML volume in the targeted compartment of the knee , and relieves knee pain . Trial registration number UK . IS RCT N50380458 OBJECTIVE To determine whether a complete anterior cruciate ligament ( ACL ) tear , a frequent incidental finding on magnetic resonance imagings ( MRIs ) of individuals with established knee osteoarthritis ( OA ) , increases the risk for further knee OA progression . METHODS We examined 265 participants ( 43 % women ) with symptomatic knee OA in a 30-month , prospect i ve , natural history study of knee OA . The more symptomatic knee was imaged using MRI at baseline , 15 and 30 months . Cartilage was scored at the medial and lateral tibiofemoral joint and at the patellofemoral joint using the Whole-Organ MRI Score ( WORMS ) semi-quantitative method . Complete ACL tear was determined on baseline MRI . At each visit , knee pain was assessed using a knee-specific visual analog scale and physical function was assessed using the Western Ontario and McMaster Universities ( WOMAC ) physical function subscale . RESULTS There were 49 participants ( 19 % ) with complete ACL tear at baseline . Adjusting for age , body mass index , gender and baseline cartilage scores , complete ACL tear increased the risk for cartilage loss at the medial tibiofemoral compartment [ odds ratio ( OR ) : 1.8 , 95 % confidence interval ( CI ) : 1.1 , 3.2 ] . However , following adjustment for the presence of medial meniscal tears , no increased risk for cartilage loss was further seen ( OR : 1.1 , 95 % CI : 0.6 , 1.8 ) . Knee pain and physical function were similar over follow-up between those with and without a complete ACL tear . CONCLUSIONS Individuals with knee OA and incidental complete ACL tear have an increased risk for cartilage loss that appears to be mediated by concurrent meniscal pathology . The presence of a complete ACL tear did not influence the level of knee pain or physical function over short-term follow-up Details of the development of early knee osteoarthritis ( OA ) are largely unknown . The prevalence and progression of radiographic knee OA over 6 years in middle-aged subjects with chronic knee pain is investigated . In a prospect i ve population -based study , tibiofemoral ( TF ) and patellofemoral ( PF ) radiographs were grade d in 128 subjects ( mean age 45 ± 6.2 years ) for the presence of osteophytes and joint space narrowing ( JSN ) . Radiographic progression was defined as : ( i ) the presence of osteophytes and /or JSN in subjects with no previous OA or ( ii ) an increase in the grade and /or number of already existing osteophytes and /or JSN . Altogether 56 % ( 72/128 ) of subjects had knee OA , the majority of them was diagnosed with OA grade 1 . In 57 % of cases , radiographic OA was based on the presence of osteophytes alone versus 13 % on JSN . More than 1/3 of subjects had isolated PF joint involvement . Knee OA progression rate over 6 years was 56 % ( 71/128 ) . During 6 years , a non-linear course of radiographic OA progression with intermittent periods of progression and stabilization was observed . Individual course of OA revealed distinct subsets of radiographic progression . Osteophytosis is an important early radiographic sign of OA and its progression . Isolated PF joint involvement is a frequent expression of knee OA . In middle-aged subjects , the progression rate of knee OA over 6 years was 56 % . A non-linear course of radiographic OA progression was observed . Several radiographic subsets refer to the heterogeneity of the OA process OBJECTIVE Patellofemoral joint osteoarthritis ( PFJ OA ) contributes considerably to knee OA symptoms . This study aim ed to determine the efficacy of a PFJ-targeted exercise , education manual-therapy and taping program compared to OA education alone , in participants with PFJ OA . METHODS A r and omised , participant-blinded and assessor-blinded clinical trial was conducted in primary -care physiotherapy . 92 people aged ≥40 years with symptomatic and radiographic PFJ OA participated . Physiotherapists delivered the PFJ-targeted exercise , education , manual-therapy and taping program , or the OA-education ( control condition ) in eight sessions over 12 weeks . Primary outcomes at 3-month ( primary ) and 9-month follow-up : ( 1 ) patient-perceived global rating of change ( 2 ) pain visual analogue scale ( VAS ) ( 100 mm ) ; and ( 3 ) activities of daily living ( ADL ) subscale of the Knee injury and Osteoarthritis Outcome Score ( KOOS ) . RESULTS 81 people ( 88 % ) completed the 3-month follow-up and data analysed on an intention-to-treat basis . Between-group baseline similarity for participant characteristics was observed . The exercise , education , manual-therapy and taping program result ed in more people reporting much improvement ( 20/44 ) than the OA-education group ( 5/48 ) ( number needed to treat 3 ( 95 % confidence interval ( CI ) 2 to 5 ) ) and greater pain reduction ( mean difference : -15.2 mm , 95 % CI -27.0 to -3.4 ) . No significant effects on ADL were observed ( 5.8 ; 95 % CI -0.6 to 12.1 ) . At 9 months there were no significant effects for self-report of improvement , pain ( -10.5 mm , 95 % CI -22.7 to 1.8 ) or ADL ( 3.0 , 95 % CI -3.7 to 9.7 ) . CONCLUSION Exercise , education , manual-therapy and taping can be recommended to improve short-term patient rating of change and pain severity . However over 9-months , both options were equivalent . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry ( ACTRN12608000288325 ) : https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=82878 Purpose To examine articular cartilage and subchondral bone changes in tibiofemoral and patellofemoral joints following partial medial meniscectomy . Methods For this cross-sectional study , 158 patients aged 30–55 years , without evidence of knee osteoarthritis at arthroscopic partial medial meniscectomy ( APMM ) , and 38 controls were recruited . MRI was performed once on the operated knee for each subcohort of 3 months , 2 or 4 years post-surgery , and the r and omly assigned knee of the controls . Cartilage volume , cartilage defects , and bone size were assessed using vali date d methods . Results Compared with controls , APMM patients had more prevalent cartilage defects in medial tibiofemoral ( OR = 3.17 , 95%CI 1.24–8.11 ) and patellofemoral ( OR = 13.76 , 95%CI 1.52–124.80 ) compartments , and increased medial tibial plateau bone area ( B = 143.8 , 95%CI 57.4–230.2 ) . Time from APMM was positively associated with cartilage defect prevalence in medial tibiofemoral ( OR = 1.02 , 95%CI 1.00–1.03 ) and patellofemoral ( OR = 1.04 , 95%CI 1.01–1.07 ) compartments , and medial tibial plateau area ( B = 2.5 , 95%CI 0.8–4.3 ) , but negatively associated with lateral tibial cartilage volume ( B = −4.9 , 95%CI −8.4 to −1.5 ) . The association of APMM and time from APMM with patellar cartilage defects was independent of tibial cartilage volume . Conclusions Partial medial meniscectomy is associated with adverse effects on articular cartilage and subchondral bone , which are associated with subsequent osteoarthritis , in both tibiofemoral and patellofemoral compartments . Level of evidence III OBJECTIVE Prevalence and clinical relevance of patellofemoral ( PF ) osteoarthritis ( OA ) after anterior cruciate ligament ( ACL ) injury . METHOD Prospect ively we studied 94 out of 100 consecutive patients 15 years after acute ACL injury . ACL reconstructions were only performed late if recurrent " give way " persisted or a secondary meniscal injury suitable for repair occurred . The subjects , mean age 42 years , had knee radiographs including skyline PF view taken , which were grade d according to the atlas of the Osteoarthritis Research Society International . Knee-related symptoms and function were assessed by question naires . RESULTS PF OA was present in 12/75 knees ( 16 % ) . Of 94 patients 22 ( 23 % ) have had their ACL reconstructed during follow-up . Meniscal injury and ACL reconstruction had occurred more often in knees with PF OA than in knees without PF OA ( P=0.004 and P=0.002 , respectively ) . Seven of 15 ACL reconstructed knees showed radiographic PF OA at follow-up . Knees with PF OA had more extension and flexion deficit than knees without PF OA . Subjects with PF OA maintained a higher activity level from injury to follow-up , but did not differ significantly from those without PF OA regarding patient-relevant symptoms and knee function . However , there was a trend for worse outcome in subjects with PF OA . CONCLUSION We found a relatively low prevalence of mild PF OA after ACL injury treated non-operatively , and it had limited impact on knee symptoms and patient-relevant knee function . At follow-up PF OA was associated with higher activity level , meniscal injury , extension and flexion deficit , and ACL reconstruction OBJECTIVE Few risk factors for knee osteoarthritis ( OA ) are appreciated , and the discordance between symptoms and the severity of structural disease has not been explained . Knee height contributes to moments around the knee . The longer the leg , the more torque is present . Although this would suggest that having long legs would be related to the occurrence of knee OA and pain , this issue has not been studied . Our aim was to explore the association between knee height , knee pain , and knee OA . METHODS We recruited a r and om sample of Beijing residents ages 60 years and older . Subjects answered questions about joint symptoms , and radiographs of their knees were obtained . A knee joint with a Kellgren/Lawrence grade of > /=2 was defined as having radiographic OA . Patellofemoral OA was defined as being present when grade > /=1 osteophytes or grade > /=1 joint space narrowing was observed on skyline views of the patella or anterior femur . Subjects were considered to have symptomatic OA when both radiographic OA and self-reported pain were present in the same joint . Knee height was measured on the right leg using a sliding broad-blade caliper ; the subject was seated , and the subject 's feet were bare . We used logistic regression analyses to assess whether knee height was associated with prevalent radiographic and symptomatic OA . We then assessed whether knee height was associated with knee symptoms independently of structural change . RESULTS A total of 1,006 men ( mean + /- SD age 68.4 + /- 6.4 years ) and 1,500 women ( mean + /- SD age 67.5 + /- 6.1 years ) participated in this study . Higher knee height was associated with an increasing prevalence of both radiographic and symptomatic OA , especially among women . For radiographic OA , the magnitude of association was similar for the patellofemoral and tibiofemoral compartments . Among women with knee pain , higher knee height was associated with more severe knee pain ( P = 0.0004 for the highest quartile versus the lowest quartile of knee height ) independently of the severity of radiographic OA . CONCLUSION Knee height is associated with prevalent radiographic and symptomatic knee OA . It may also play an important role in knee symptoms . This study highlights the importance of mechanical forces in the determination of OA and knee symptoms Abstract : In this cross-sectional study we looked at the radiographic evidence of osteoarthritis ( OA ) of the knee in 300 r and omly chosen patients attending 14 primary care facilities for different medical conditions . Radiographic OA was seen in 89 out of 167 males ( 53.3 % ) and in 81 out of 133 females ( 60.9 % ) . The patella was involved with radiographic osteoarthritic changes in 80.7 % and 87.8 % of female and male OA patients , respectively . In most cases the medial compartment joint space was narrowed . Radiographic OA of the knee is very common in Saudi patients , especially in the patellofemoral compartment PURPOSE The number of effective knee osteoarthritis ( OA ) interventions , especially those tailored to specific compartmental involvement , are small . The objective of this study was to determine the efficacy of a realigning patellofemoral ( PF ) brace in improving pain and function among persons with symptomatic lateral PF OA . METHOD We conducted a double blind , r and omized crossover trial of a realigning PF brace for persons with lateral PF OA . Participants had lateral PF OA with anterior knee symptoms on most days of the month , lateral PF joint space narrowing , and radiographic evidence of a definite osteophyte in the PF joint . We compared two treatments : ( 1 ) Control treatment consisting of a BioSkin Q Brace with patellar realigning strap removed ; and ( 2 ) Active treatment consisting of a realigning BioSkin Q Brace with the strap applied . For each participant , the trial lasted 18 weeks , including 6 weeks each of active and control treatment period separated by a 6-week washout period . The order of treatments was r and omized . The primary outcome was change in knee pain on the visual analog scale ( VAS ) . Secondary outcomes included WOMAC pain , function , and stiffness . An unstructured correlation matrix for observations within participants was used in generalized estimating equation fitting to derive a linear regression model that expressed the relation between the intervention and change in VAS pain . RESULTS 80 participants ( 63 F ) with a mean age and body mass index of 61 years and 28 kg/m(2 ) , respectively , were r and omized by order of treatment . A model examining the main effects for change in VAS knee pain ( 0 - 100 ) demonstrated no significant treatment effect ( -0.68 VAS units , 95 % CI : -6.2 , 4.8 units , P=0.81 ) and no differential carryover effect . There was also no significant difference between active and control treatments for WOMAC pain , function , or stiffness outcomes . CONCLUSION The effects of a specific realigning PF brace are not of clinical or statistical significance Background There are still controversies about graft selection for primary anterior cruciate ligament reconstruction . Prospect i ve r and omized long-term studies are needed to determine the differences between the material s. Hypothesis Five years after anterior cruciate ligament reconstruction , there is a difference between hamstring and patellar tendon grafts in development of degenerative knee joint disease . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods From June 1999 to March 2000 , 64 patients were included in this prospect i ve study . A single surgeon performed primary arthroscopically assisted anterior cruciate ligament reconstruction in an alternating sequence . In 32 patients , anterior cruciate ligament reconstruction was performed with hamstring tendon autograft , whereas in the other 32 patients , anterior cruciate ligament reconstruction was performed with patellar tendon autograft . Results At the 5-year follow-up , no statistically significant differences were seen with respect to the Lysholm score , clinical and KT-2000 arthrometer laxity testing , anterior knee pain , single-legged hop test , or International Knee Documentation Committee classification results ; 23 patients ( 82 % ) in the hamstring tendon group and 23 patients ( 88 % ) in the patellar tendon group returned to their preinjury activity levels . Graft rupture occurred in 2 patients from the hamstring tendon group ( 7 % ) and in 2 patients from the patellar tendon group ( 8 % ) . Grade B abnormal radiographic findings were seen in 50 % ( 13/26 ) of patients in the patellar tendon group and in 17 % ( 5/28 ) of patients in the hamstring tendon group ( P = . 012 ) . Conclusion Both hamstring and patellar tendon grafts provided good subjective outcomes and objective stability at 5 years . No significant differences in the rate of graft failure were identified . Patients with patellar tendon grafts had a greater prevalence of osteoarthritis at 5 years after surgery OBJECTIVE In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools , integrating expert readers ' experience with all available scoring tools and the published data comparing the different scoring systems , we iteratively developed the magnetic resonance imaging ( MRI ) Osteoarthritis Knee Score ( MOAKS ) . The purpose of this report is to describe the instrument and its reliability . METHODS The MOAKS instrument refines the scoring of bone marrow lesions ( BMLs ) ( providing regional delineation and scoring across regions ) , cartilage ( sub-regional assessment ) , and refines the elements of meniscal morphology ( adding meniscal hypertrophy , partial maceration and progressive partial maceration ) scoring . After a training and calibration session two expert readers read MRIs of 20 knees separately . In addition , one reader re-read the same 20 MRIs 4 weeks later presented in r and om order to assess intra-rater reliability . The analyses presented here are for both intra- and inter-rater reliability ( calculated using the linear weighted kappa and overall percent agreement ) . RESULTS With the exception of inter-rater reliability for tibial cartilage area ( kappa=0.36 ) and tibial osteophytes ( kappa=0.49 ) ; and intra-rater reliability for tibial BML number of lesions ( kappa=0.54 ) , Hoffa-synovitis ( kappa=0.42 ) all measures of reliability using kappa statistics were very good ( 0.61 - 0.8 ) or reached near-perfect agreement ( 0.81 - 1.0 ) . Only intra-rater reliability for Hoffa-synovitis , and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement < 75 % . CONCLUSION MOAKS scoring shows very good to excellent reliability for the large majority of features assessed . Further iterative development and research will include assessment of its validation and responsiveness OBJECTIVE To determine the effect of weight and physical activity on the prevalence of radiological knee osteoarthritis ( OA ) in a cohort of middle-aged women . METHODS The longitudinal phase of the Melbourne Women 's Mid-life Health Project is a population -based prospect i ve study of 438 Australian-born women who have been followed annually over 11 years . Of these women , 257 ( 59 % ) remained in longitudinal assessment at eleventh year of followup , and 224 of these women agreed to undergo radiographs of their knees . Radiographs were scored for features of OA [ osteophytes and joint space narrowing ( JSN ) ] using a vali date d scale , by 2 investigators who were blinded to question naire results . Data were obtained by both self-administered and face-to-face interview question naires . RESULTS The average weight increase over the study period of 11 years was 4 kg ( range -14 to 25 kg ) . Of the 224 women evaluated , 65 ( 29 % ) had knee joint osteophytes and 95 ( 42 % ) had evidence of knee JSN . Current weight and weight at baseline were independent factors associated with a higher prevalence of both osteophytes and JSN in all compartments of the knee . The average amount of physical activity over the 11 years of followup was a significant factor independently associated with an increased prevalence of patellofemoral JSN and approached significance for tibiofemoral osteophytes and total knee JSN . CONCLUSION Our study supports a longterm detrimental effect of weight on the knee joint and suggests the importance of longterm weight maintenance programs in preventing knee OA . The average amount of physical activity was associated with an increased prevalence of some features of knee OA PURPOSE To prospect ively compare magnetic resonance ( MR ) imaging-defined abnormalities of osteoarthritis ( OA ) of the knee with radiographic severity measurements of OA of the knee and self-reported pain . MATERIAL S AND METHODS This study was approved by the institutional review board of University of Michigan . Informed consent was obtained for this HIPAA-compliant study . Knee MR imaging was performed in 117 women ( mean age , 46 years ; range , 32 - 56 years ) from a community-based arthritis study ( n = 1053 ) with 30 women in each of four categories : ( a ) no pain and no OA of the knee , ( b ) no pain and OA of the knee , ( c ) pain and no OA of the knee , and ( d ) pain and OA of the knee . OA of the knee was defined from radiographs . Two hundred thirty-two eligible knees had Kellgren-Lawrence scores for OA of the knee as follows : grade 0 , 115 ( 49.6 % ) ; grade 1 , 33 ( 14.2 % ) ; grade 2 , 66 ( 28.4 % ) ; grade 3 , 17 ( 7.3 % ) ; and grade 4 , one ( 0.4 % ) . MR images were assessed for location and severity of defects of cartilage , bone marrow edema ( BME ) , osteophytes , subchondral cysts , sclerosis , meniscal and /or ligamentous tears , joint effusion , synovial cysts , and synovitis . MR imaging findings were compared with radiographic severity of OA of the knee ( Kellgren-Lawrence scale ) and self-reported pain with analysis of variance , t tests , and contingency table analyses . RESULTS Defects of cartilage ( higher than grade IIA ) were found in 75 % of knees ; BME was found in 57 % of knees ( < 1 cm , 41 % ; > 1 cm , 16 % ) . Large BME lesions were common in the pain and OA of the knee group ( P = .001 ) ; this group was significantly more likely to have defects of cartilage ( P = .001 ) ; meniscal tears ( P = .001 ) ; and osteophytes , subchondral cysts , sclerosis , joint effusion , and synovitis ( P < .001 ) . Defects of cartilage , osteophytes , sclerosis , meniscal or ligamentous tears , joint effusion , and synovitis were strongly related to increasing Kellgren-Lawrence grade ( P < .001 ) . CONCLUSION In middle-aged women , there were significant associations between pain , radiographic severity of OA of the knee , and seven MR imaging-identified parameters Background : The reported prevalence of radiological osteoarthritis ( OA ) after anterior cruciate ligament ( ACL ) reconstruction varies from 10 % to 90 % . Purpose /Hypothesis : To report the prevalence of OA after ACL reconstruction and to compare the OA prevalence between quadrupled semitendinosus tendon ( ST ) and bone – patellar tendon – bone ( BPTB ) grafts . The hypothesis was that there would be no difference in OA prevalence between the graft types . The secondary aim was to study whether patient characteristics and additional injuries were associated with long-term outcomes . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Radiological examination results , Tegner activity levels , and Knee injury and Osteoarthritis Outcome Score ( KOOS ) values were determined in 135 ( 82 % ) of 164 patients at a mean of 14 years after ACL reconstruction r and omized to an ST or a BPTB graft . Osteoarthritis was defined according to a consensus by at least 2 of 3 radiologists of Kellgren-Lawrence grade ≥2 . Using regression analysis , graft type , sex , age , overweight , time between injury and reconstruction , additional meniscus injury , and a number of other variables were assessed as risk factors for OA 14 years after ACL reconstruction . Results : Osteoarthritis of the medial compartment was most frequent , with 57 % of OA cases in the ACL-reconstructed knee and 18 % of OA cases in the contralateral knee ( P < .001 ) . There was no difference between the graft types : 49 % of OA of the medial compartment for BPTB grafts and 65 % for ST grafts ( P = .073 ) . The KOOS results were lower for patients with OA in all subscales , indicating that OA was symptomatic . No difference in the KOOS between the graft types was found . Meniscus resection was a strong risk factor for OA of the medial compartment ( odds ratio , 3.6 ; 95 % CI , 1.4 - 9.3 ) in the multivariable logistic regression analysis . Conclusion : A 3-fold increased prevalence of OA was found after an ACL injury treated with reconstruction compared with the contralateral healthy knee . No differences in the prevalence of OA between the BPTB and quadrupled ST reconstructions were found . An initial meniscus resection was a strong risk factor for OA ; the time between injury and reconstruction was not |
10,341 | 22,792,014 | For second-line treatment after fluoropyrimidine monotherapy , folfox is a reasonable alternative for patients with contraindications to second-line irinotecan .
Evidence from a single r and omized trial suggests that additional benefits can be expected with the addition of bevacizumab to the folfox regimen in second-line treatment .
The folfox regimen has superior rates of median survival and tumour response .
Compared with ifl , folfox has lower incidences of severe nausea , vomiting , diarrhea , and febrile neutropenia , but a higher incidence of peripheral neuropathy .
The folfox regimen is a reasonable alternative for patients with contraindications to the use of second-line irinotecan .
After progression on both irinotecan and an anti-thymidylate synthase agent , folfox is the preferred therapy .
Recent trials suggest that , as compared with folfox alone , folfox combined with bevacizumab provides additional survival benefits . | QUESTION What is the role of oxaliplatin combined with 5-fluorouracil ( 5-fu ) and folinic acid ( fa ) in the first- and second-line treatment of advanced ( unresectable locally advanced or metastatic ) colorectal cancer ? | PURPOSE In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different PURPOSE In North America , no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan , bolus fluorouracil ( FU ) , and leucovorin ( IFL ) . PATIENTS AND METHODS Patients with metastatic colorectal cancer who progressed after IFL therapy were r and omly assigned to bolus and infusional FU and leucovorin ( LV5FU2 ) , single-agent oxaliplatin , or the combination ( FOLFOX4 ) . This planned interim analysis evaluated objective response rate ( RR ) , time to tumor progression ( TTP ) , and alleviation of tumor-related symptoms ( TRS ) in an initial cohort of patients . RESULTS Between November 2000 and September 2001 , 463 patients from 120 sites in North America were r and omly assigned to treatment . FOLFOX4 proved superior to LV5FU2 in all measures of clinical efficacy . Objective RRs determined by an independent radiology panel were 9.9 % for FOLFOX4 versus 0 % for LV5FU2 ( Fisher 's exact test , P < .0001 ) . Median TTP was 4.6 months for FOLFOX4 versus 2.7 months for LV5FU2 ( two-sided , stratified log-rank test , P < .0001 ) . Relief of TRS occurred in 33 % of patients treated with FOLFOX4 versus 12 % of patients treated with LVFU2 ( chi2 test , P < .001 ) . Single-agent oxaliplatin was not superior to LV5FU2 in any measure of efficacy . Patients treated with FOLFOX4 experienced a higher incidence of clinical ly significant toxicities than patients treated with LV5FU2 , but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate . CONCLUSION For patients with metastatic colorectal cancer , second-line treatment with FOLFOX4 is superior to treatment with LVFU2 in terms of RR , TTP , and relief of TRS PURPOSE We performed this phase III study to compare the irinotecan , leucovorin ( LV ) , and fluorouracil ( FU ) regimen ( FOLFIRI ) versus the oxaliplatin , LV , and FU regimen ( FOLFOX4 ) in previously untreated patients with advanced colorectal cancer . PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were r and omly assigned to receive , every 2 weeks , either arm A ( FOLFIRI : irinotecan 180 mg/m(2 ) on day 1 with LV 100 mg/m(2 ) administered as a 2-hour infusion before FU 400 mg/m(2 ) administered as an intravenous bolus injection , and FU 600 mg/m(2 ) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [ LV5FU2 ] ) or arm B ( FOLFOX4 : oxaliplatin 85 mg/m(2 ) on day 1 with LV5FU2 regimen ) . RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B , respectively . Overall response rates ( ORR ) were 31 % in arm A ( 95 % CI , 24.6 % to 38.3 % ) and 34 % in arm B ( 95 % CI , 27.2 % to 41.5 % ; P = .60 ) . In both arms A and B , median time to progression ( TTP ; 7 v 7 months , respectively ) , duration of response ( 9 v 10 months , respectively ) , and overall survival ( OS ; 14 v 15 months , respectively ) were similar , without any statistically significant difference . Toxicity was mild in both groups : alopecia and gastrointestinal disturbances were the most common toxicities in arm A ; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms , and no statistical significant difference was observed . CONCLUSION There is no difference in ORR , TTP , and OS for patients treated with the FOLFIRI or FOLFOX4 regimen . Both therapies seemed effective as first-line treatment in these patients . The difference between these two combination therapies is mainly in the toxicity profile PURPOSE To determine the activity of biweekly oxaliplatin , combined with weekly bolus fluorouracil ( FU ) and low-dose leucovorin ( LV ) chemotherapy ( bFOL ) , as first-line therapy for patients with metastatic colorectal cancer . PATIENTS AND METHODS Patients with measurable metastatic colorectal cancer ; no previous therapy for advanced disease ( adjuvant therapy allowed if > 6 months since completion ) ; and performance status 0 , 1 , or 2 were eligible and were treated with oxaliplatin 85 mg/m2 days 1 and 15 plus LV 20 mg/m2 over 10 to 20 minutes , followed by a 500 mg/m2 bolus dose of FU on days 1 , 8 , and 15 every 28 days . Patients underwent response evaluation by computed tomographic scan every 2 months . RESULTS Forty-two patients were entered , and 41 patients were treated , including 20 men and 22 women , nine with previous adjuvant chemotherapy and four with radiation therapy . Three patients achieved complete response , and 23 patients achieved partial response , for a response rate of 63 % ( 95 % CI , 49 % to 78 % ) . Major toxicities included cumulative neuropathy grade 2 ( 24 % ) and grade 3 ( 12 % ; requiring discontinuation of oxaliplatin ) , diarrhea grade 3 to 4 ( 29 % ) and grade 3 to 4 hematologic toxicity ( 10 % ) . Median time to progression was 9.0 months ( 95 % confidence interval , 7.1 to 10.8 months ) with median survival of 15.9 months ( 95 % confidence interval , 11.4 to 19.7 months ) . CONCLUSION The bFOL regimen seems to have activity comparable to be infusional programs of FU combined with oxaliplatin . Prospect i ve trials are warranted to determine the relative merits of this schedule compared with the currently indicated schedules PURPOSE In a previous study of treatment for advanced colorectal cancer , the LV5FU2 regimen , comprising leucovorin ( LV ) plus bolus and infusional fluorouracil ( 5FU ) every 2 weeks , was superior to the st and ard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen . This phase III study investigated the effect of combining oxaliplatin with LV5FU2 , with progression-free survival as the primary end point . PATIENTS AND METHODS Four hundred twenty previously untreated patients with measurable disease were r and omized to receive a 2-hour infusion of LV ( 200 mg/m(2)/d ) followed by a 5FU bolus ( 400 mg/m(2)/d ) and 22-hour infusion ( 600 mg/m(2)/d ) for 2 consecutive days every 2 weeks , either alone or together with oxaliplatin 85 mg/m(2 ) as a 2-hour infusion on day 1 . RESULTS Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival ( median , 9.0 v 6.2 months ; P = .0003 ) and better response rate ( 50.7 % v 22.3 % ; P = .0001 ) when compared with the control arm . The improvement in overall survival did not reach significance ( median , 16.2 v 14.7 months ; P = . 12 ) . LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia ( 41 . 7 % v 5.3 % of patients ) , grade 3/4 diarrhea ( 11.9 % v 5.3 % ) , and grade 3 neurosensory toxicity ( 18.2 % v 0 % ) , but this did not result in impairment of quality of life ( QoL ) . Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment ( P = .004 ) . CONCLUSION The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer , demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of |
10,342 | 25,675,398 | Significant effects on pain and function were determined .
A slight effect on kinematics of the lower limb and muscle activation of selected lower limb muscles was identified .
Foot orthoses seem to be an effective treatment device in the therapy for PFPS .
An immediate and long-term reduction in pain and an improvement of function occurred following the intervention .
There was just a slight change in lower limb kinematics and muscle activation of selected lower limb muscles .
The relationship between biomechanical effects of orthoses and pain still seems to be unclear | BACKGROUND The patellofemoral pain syndrome ( PFPS ) is one of the most commonly encountered disorders involving the knee .
The symptoms often lead to a reduction of physical activities result ing in sport- and job-related disabilities and the potential occurrence of severe disorders .
Different theories for the development of the syndrome exist which result in different therapy modalities .
A change in foot posture and its effect on lower limb kinematics seem to be one potential risk factor for the development of the syndrome .
This leads to the assumption that foot orthoses might be a potential therapy device .
OBJECTIVES The aims of this study were to outline the state of evidence for the treatment of PFPS with foot orthoses and to identify the effect of foot orthoses on PFPS . | Objectives Describe proportions of individuals with patellofemoral pain ( PFP ) with an unfavourable recovery over 12 months ; identify clinical predictors of poor recovery at 3 and 12 months ; and determine baseline values of predictors that identify those with poor 12-month prognosis . Methods An observational analysis utilised data from 310 individuals with PFP enrolled in two r and omised clinical trials . Thirteen baseline variables ( participant , PFP , study characteristics ) were investigated for their prognostic ability . Pain , function and global recovery were measured at 3 and 12 months . Multivariate backward stepwise regression analyses ( treatment-adjusted , p<0.10 ) were performed for each follow-up measure . Receiver operator characteristic curves identified cut-points associated with unfavourable recovery at 12 months . Results 55 % and 40 % of participants had an unfavourable recovery at 3 and 12 months , respectively . Longer baseline pain duration was significantly associated with poor 3-month and 12-month recovery on measures of pain severity ( β 11.36 to 24.94 ) , Anterior Knee Pain ( AKP ) Scale ( −4.44 to −11.33 ) and global recovery ( OR : 2.32 to 6.11 ) . Greater baseline pain severity and lower AKP Scale score were significantly associated with poor recovery on multiple measures ( p<0.05 ) . Baseline duration > 2 months and AKP Scale score < 70/100 were associated with unfavourable 12-month recovery . Conclusions A substantial number of individuals with PFP have an unfavourable recovery over 12 months , irrespective of intervention . Knee pain duration > 2 months is the most consistent prognostic indicator , followed by AKP Scale score < 70 . Sports medicine practitioners should utilise interventions with known efficacy in reducing PFP , and promote early intervention to maximise prognosis . Trial registration Australian study : Australian Clinical Trials Registry ( ACTRN012605000463673 ) , Clinical Trials.gov ( NCT00118521 ) ; Dutch study : International St and ard R and omised Controlled Trial Number Register ( IS RCT N83938749 We examined the effects of medially wedged foot orthoses on knee and hip joint mechanics during running in females with and without patellofemoral pain syndrome ( PFPS ) . We also tested if these effects depend on st and ing calcaneal eversion angle . Twenty female runners with and without PFPS participated . Knee and hip joint transverse and frontal plane peak angle , excursion , and peak internal knee and hip abduction moment were calculated while running with and without a 6 ° full-length medially wedged foot orthoses . Separate 3-factor mixed ANOVAs ( group [ PFPS , control ] x condition [ medial wedge , no medial wedge ] x st and ing calcaneal angle [ everted , neutral , inverted ] ) were used to test the effect of medially wedged orthoses on each dependent variable . Knee abduction moment increased 3 % ( P = .03 ) and hip adduction excursion decreased 0.6 ° ( P < .01 ) using medially wedged foot orthoses . No significant group x condition or calcaneal angle x condition effects were observed . The addition of medially wedged foot orthoses to st and ardized running shoes had minimal effect on knee and hip joint mechanics during running thought to be associated with the etiology or exacerbation of PFPS symptoms . These effects did not appear to depend on injury status or st and ing calcaneal posture Anterior knee pain ( AKP ) is a common injury among runners and effectively treated with posted insoles and foot orthotics . While clinical ly effective , the underlying biomechanical mechanisms that bring about these improvements remain debatable . Several method ological factors contribute to the inconsistent biomechanical findings , including errors associated with removing and reattaching markers , inferring foot motion from markers placed externally on a shoe , and redefining segmental coordinate systems between conditions . Therefore , the purpose of this study was to evaluate the influence of medially posted insoles on lower extremity kinematics in runners with and without AKP while trying to limit the influence of these method ological factors . Kinematics of 16 asymptomatic and 17 runners with AKP were collected while running with and without insoles . Reflective markers were attached to the surface of the calcaneus and kept in place ( as opposed to detached ) between conditions , eliminating the error associated with reattaching markers and redefining segmental coordinate systems . Using these methods , no significant interactions between insole and injury and the main effect of injury were detected ( p>0.05 ) ; therefore , means were pooled across injury . Insoles , on average , reduced peak eversion by 3.6 ° ( 95 % confidence interval -2.9 ° to -4.3 ° ) , peak eversion velocity by 53.2 ° /s ( 95 % confidence interval -32.9 to -73.4 ) and eversion range of motion by 1.33 ( 95 % confidence interval -0.8 to -1.9 ) . However , while insoles systematic ally reduced eversion variables , they had small influences on the transverse plane kinematics of the tibia or knee , indicating that they may bring about their clinical effect by influencing other variables Treadmills are often used in research to analyse kinematic and physiological variables . The success of transfering the results to overground running depends on the comparability of the values between the two situations . The aim of the present study was to compare the kinematics and muscle activities in overground and treadmill running . Ten male physical education students with experience in treadmill running were asked to run with a speed of 4.0 and 6.0 m/s both overground and on a Woodway treadmill . The 3D-kinematics of the limbs were studied using a two camera video tracking system . Additionally the surface EMG of six lower limb muscles and the pattern of ground contact of the right foot was registered . Both the activities of the leg muscles and several kinematic variables showed systematic changes from overground to treadmill running . On the treadmill the subjects favoured a type of running that provided them with a higher level of security . The swing amplitude of the leg , the vertical displacement and the variance in vertical and horizontal velocity were lower in treadmill running . The angle between shoe sole and ground at foot impact was also lower and the forward lean of the upper body was higher in running on the treadmill compared with the overground mode . Most of the subjects reduced their step length and increased stride frequency in treadmill running . Furthermore , the contact time in treadmill running was shorter than for overground running . The above mentioned kinematic variables were significantly different ( p < 0.05 ) . The EMG patterns of the leg muscles were generally similar between overground and treadmill modes , but some minor differences could consistently be identified OBJECTIVE To examine the test-retest reliability , validity , and responsiveness of several outcome measures in the treatment of patellofemoral pain . DESIGN Evaluation of the clinimetric properties of individual outcome measures for patellofemoral pain treatment , using data collected from a previously published r and omized controlled trial ( RCT ) . SETTING General community and private practice . PARTICIPANTS The data from 71 persons enrolled in an RCT of a conservative intervention for patellofemoral pain were used to evaluate the measures ' validity and responsiveness . A subset of this cohort ( n=20 ) was used to assess reliability . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Three 10-cm visual analog scales ( VASs ) for usual pain ( VAS-U ) , worst pain ( VAS-W ) , and pain on 6 aggravating activities ( walking , running , squatting , sitting , ascending and descending stairs ) ( VAS-activity ) ; the Functional Index Question naire ( FIQ ) ; the Anterior Knee Pain Scale ( AKPS ) ; and the global rating of change . RESULTS The test-retest reliability ranged from poor ( intraclass correlation coefficient [ICC]=.49 ) to good ( ICC=.83 ) , and the measures correlated moderately with each other ( r range,.56-.72 ) . Median change scores differed significantly between improved and unimproved persons for all measures . The effect sizes for VAS-U ( .79 ) , VAS-W ( .88 ) , and the AKPS ( .98 ) were large , indicating greater responsiveness than the FIQ ( .37 ) and VAS-activity ( .66 ) . Similarly , the AKPS and VAS-W were the most efficient measures for detecting a treatment effect when compared with a reference measure ( VAS-U , which was assigned a value of 1 ) . The minimal difference that patients or clinicians consider clinical ly important for the AKPS is 10 ( out of 100 ) points and for the VAS it is 2 cm ( out of 10 cm ) . CONCLUSIONS The AKPS and VAS for usual or worst pain are reliable , valid , and responsive and are therefore recommended for future clinical trials or clinical practice in assessing treatment outcome in persons with patellofemoral pain BACKGROUND Excessive rearfoot eversion is thought to be a risk factor for patellofemoral pain syndrome development , based on theoretical rationale linking it to greater tibial internal rotation and hip adduction . This study aim ed to establish the relationship of rearfoot eversion with tibial internal rotation and hip adduction during walking in individuals with and without patellofemoral pain syndrome . METHODS Twenty-six individuals with patellofemoral pain syndrome and 20 controls ( 18 - 35years ) participated . Each underwent instrumented three-dimensional motion analysis during over-ground walking . Pearson 's correlation coefficients ( r ) were calculated to establish the relationship of rearfoot eversion with tibial internal rotation and hip adduction ( peak and range of motion ) . FINDINGS Greater peak rearfoot eversion was associated with greater peak tibial internal rotation in the patellofemoral pain syndrome group ( r=0.394 , P=0.046 ) . Greater rearfoot eversion range of motion was associated with greater hip adduction range of motion in the patellofemoral pain syndrome ( r=0.573 , P=0.002 ) and control ( r=0.460 , P=0.041 ) groups ; and greater peak hip adduction in the control group ( r=0.477 , P=0.033 ) . INTERPRETATION Associations between greater rearfoot eversion and greater hip adduction indicate that interventions targeted at the foot or hip in individuals with patellofemoral pain syndrome may have similar overall effects on lower limb motion and clinical outcomes . The relationship between rearfoot eversion and tibial internal rotation identified in the patellofemoral pain syndrome group may be related to aetiology . However , additional prospect i ve research is needed to confirm this OBJECTIVES This study evaluated the effects of unmodified prefabricated foot orthoses over a 12-week period on functional performance ; and subjective pain and function in individuals with patellofemoral pain syndrome ( PFPS ) . DESIGN Prospect i ve cohort study over 12 weeks . Each participant was prescribed prefabricated foot orthoses at baseline . PARTICIPANTS Sixty individuals with PFPS ( 18 - 35 years ) . MAIN OUTCOME MEASURES Change in pain and ease of completing a single leg squat ; change in the number of pain free step downs and single leg rises from sitting ; usual and worst pain in the previous week ; the anterior knee pain scale ( AKPS ) ; and the lower extremity functional scale ( LEFS ) . RESULTS At 12 weeks , significant improvements in single leg squat pain and ease , and the number of pain free step downs and single leg rises from sitting were found . Additionally , significant reductions in usual and worst pain , and improvements on the AKPS and LEFS were observed . CONCLUSIONS Functional performance improvements following unmodified prefabricated foot orthoses were greater at 12 weeks that those achieved immediately . Enhanced functional performance over time may have significant implication s for osteoarthritis prevention in some individuals with PFPS . Improvements in subjective pain and function appear to plateau over time BACKGROUND AND PURPOSE The effectiveness of soft foot orthotics in the treatment of patients who have patellofemoral pain syndrome was investigated . SUBJECTS Subjects were 20 adolescent female patients , aged 13 to 17 years ( mean = 14.8 , SD = 1.2 ) , who were diagnosed with patellofemoral pain syndrome and who exhibited excessive forefoot varus or calcaneal valgus . METHODS Subjects were r and omly assigned to one of two groups : a control group ( n = 10 ) , which took part in an exercise program , or a treatment group ( n = 10 ) , which used soft foot orthotics in addition to participating in the exercise program . The exercise program consisted of quadriceps femoris and hamstring muscle strengthening and stretching exercises . A visual analogue scale was used to assess the level of pain of the subjects over an 8-week period . RESULTS Both the treatment and control groups demonstrated a significant decrease in the level of pain , but the improvement of the treatment group was significantly greater than that of the control group . CONCLUSION AND DISCUSSION The results suggest that in addition to an exercise program , the use of soft foot orthotics is an effective means of treatment for the patient with patellofemoral pain syndrome BACKGROUND The aims of this study were to determine the prevalence and incidence of patellofemoral pain ( PFP ) in young female athletes and prospect ively evaluate measures of frontal plane knee loading during l and ing to determine their relationship to development of PFP . We hypothesized that increased dynamic knee abduction measured during preseason biomechanical testing would be increased in those who developed PFP relative to teammates who did not develop PFP . METHODS Middle and high school female athletes ( n=240 ) were evaluated by a physician for PFP and for l and ing biomechanics prior to their basketball season . The athletes were monitored for athletic exposures and PFP injury during their competitive seasons . FINDINGS At the beginning of the season , the point prevalence of PFP was 16.3 per 100 athletes . The cumulative incidence risk and rate for the development of new unilateral PFP was 9.66 per 100 athletes and 1.09 per 1000 athletic exposures , respectively . All new PFPs developed in middle school athletes who demonstrated mean International Knee Documentation Committee score of 85.6+/-7.7 at diagnosis . The new PFP group demonstrated increased knee abduction moments at initial contact ( 95 % CI : 0.32 to 4.62Nm ) on the most-symptomatic limb and maximum ( 95 % CI : 1.3 to 10.1Nm ; P=0.02 ) on the least-symptomatic ( or no symptoms ) limb relative to the matched control limbs . Knee abduction moments remained increased in the new PFP group when normalized to body mass ( P<0.05 ) . INTERPRETATION The increased knee abduction l and ing mechanics in the new PFP group indicate that frontal plane loads contribute to increased incidence of PFP Objective : To examine the effects of foot orthosis intervention during a 60-minute running test in pronated-foot runners with overuse knee or foot pain during running . Design : A r and omized , controlled design . Setting : Sports gym . Participants : Twenty-four runners with pronated foot who experienced pain over anterior knee or foot region during running were recruited and r and omized into the treatment , or the control , group . Interventions : A soft insole with a semi-rigid rearfoot medial wedge was given to the treatment group , and a soft insole without corrective posting was applied to the control group . Outcome measures : The immediate and short-term effects of orthosis application on incidence of pain , pain intensity and onset time were evaluated using the 60-minutes treadmill test . Results : Immediately after wearing the foot orthosis , pain incidence reduced in the treatment group but not in the control group ( P = 0.04 ) . After two weeks , seven ( 58 % ) subjects in the treatment group and one ( 8 % ) in the control group were free of pain during the test ( P = 0.01 ) . The pain intensity score decreased significantly after orthosis application , from 35.5 to 17.2 ( immediate effect , P = 0.014 ) , then to 12.3 ( short-term effect , P < 0.001 ) . Conclusion : The rearfoot medially-wedged insole was a useful intervention for preventing or reducing painful knee or foot symptoms during running in runners with pronated foot Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles Background Identification of mechanical factors associated with patellofemoral pain , the most prevalent running injury , is necessary to help in injury prevention , but unfortunately they remain elusive . Hypothesis Runners who develop patellofemoral pain have increased knee joint angular impulse in the frontal plane . Study Design Case control study ; Level of evidence , 3 . Methods A retrospective study compared knee abduction impulses of 20 patellofemoral pain patients with those of 20 asymptomatic patients . A second prospect i ve study quantified knee angular impulses during the stance phase of running of 80 runners at the beginning of the summer running season . Epidemiologic data were then collected , recording the type and severity of injury of these runners during a 6-month running period . Results The patellofemoral pain patients in the retrospective study had significantly higher ( P = . 026 ) knee abduction impulses ( 17.0 ± 8.5 Nms ) than did the asymptomatic patients ( 12.5 ± 5.5 Nms ) . Six patients developed patellofemoral pain during the prospect i ve study . The prospect i ve data showed that patients who developed patellofemoral pain had significantly higher ( P = . 042 ) knee abduction impulses ( 9.2 ± 3.7 Nms ) than did matched patients who remained uninjured ( 4.7 ± 3.5 Nms ) . Conclusion The data indicate that increased knee abduction impulses should be deemed risk factors that play a role in the development of patellofemoral pain in runners . Clinical Relevance Footwear and running style can influence knee angular impulse , and the appropriate manipulation of these variables may play a preventive role for patients who are predisposed to patellofemoral pain Background : Patellofemoral pain is one of the most common disorders affecting the knee . Forefoot varus and excessive subtalar pronation can be associated with patellofemoral pain . Foot orthotics may produce an improvement in symptoms . Objectives : The aim of this study was to test whether patellofemoral pain is improved after four weeks of using custom-made foot orthoses . Study Design : Clinical trial without control group . Methods : Twenty-one subjects with patellofemoral pain were given custom-made foot orthoses ( 2-mm thick polypropylene and 4-mm thick polyethylene foam liner of 45 shore A hardness ) . Patellofemoral pain was evaluated with a visual analogue scale before applying the treatment , and at two weeks and four weeks follow-up . At the two-week check-up , a forefoot varus posting was added to the orthoses . Results : Improvements in patellofemoral pain was significant in all comparisons : initial pain with pain at the two-week check-up ( P<0.001 ) , initial pain with pain at four weeks ( P<0.001 ) , and pain at two weeks with pain at four weeks ( P<0.001 ) . The effect size was large in all comparisons . Conclusion : For the participants in this study , the custom-made foot orthoses were found to be an effective conservative treatment to reduce the symptoms of patellofemoral pain Many variables have retrospectively been associated with the presence of anterior knee pain . Very few prospect i ve data exist , however , to determine which of these variables will lead to the development of anterior knee pain . It was our purpose in this study to determine the intrinsic risk factors for the development of anterior knee pain in an athletic population over a 2-year period . Before the start of training , 282 male and female students enrolled in physical education classes were evaluated for anthropometric variables , motor performance , general joint laxity , lower leg alignment characteristics , muscle length and strength , static and dynamic patellofemoral characteristics , and psychological parameters . During this 2-year follow-up study , 24 of the 282 students developed patellofemoral pain . Statistical analyses revealed a significant difference between those subjects who developed patellofemoral pain and those who did not concerning quadriceps and gastrocnemius muscle flexibility , explosive strength , thumb-forearm mobility , reflex response time of the vastus medialis obliquus and vastus lateralis muscles , and the psychological parameter of seeking social support . However , only a shortened quadriceps muscle , an altered vastus medialis obliquus muscle reflex response time , a decreased explosive strength , and a hypermobile patella had a significant correlation with the incidence of patellofemoral pain . We concluded that the latter four parameters play a dominant role in the genesis of anterior knee pain and we therefore deem them to be risk factors for this syndrome STUDY DESIGN Repeated- measures analysis of intervention . OBJECTIVES To determine the effects of foot orthoses on quality of life for individuals with patellofemoral pain who demonstrate excessive foot pronation . BACKGROUND Foot orthoses are a common intervention for patients with patellofemoral pain . Limited information is available , however , regarding the effects of foot orthoses on quality of life for these patients . METHODS AND MEASURES Sixteen subjects with patellofemoral pain who also exhibited signs of excessive foot pronation were studied . Subjects underwent a 2-week period of baseline study followed by custom foot orthotic intervention . The Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) was administered to subjects at the time of screening , just prior to foot orthotic intervention , and at 2 weeks and 3 months following foot orthotic intervention . RESULTS Wilcoxon matched-pairs signed-rank test results indicated statistically significant improvements in the pain and stiffness subscales 2 weeks following the start of foot orthotic intervention . All WOMAC subscale scores were significantly improved at 3 months compared with preintervention measurements . CONCLUSIONS Custom-fitted foot orthoses may improve patellofemoral pain symptoms for patients who demonstrate excessive foot pronation |
10,343 | 30,186,824 | Conclusion : Adherence rate in children with severe asthma is not satisfactory but it can be improved after proper interventions . | Introduction : Poor adherence to inhaled medication is a commonly encountered problem among children with asthma .
However , there is a relatively paucity of data regarding the adherence of children with severe asthma , as well as the merit of any interventions to improve this adherence .
Objectives : The aim of this systematic review was to identify the available literature on the rate of adherence and the influence of interventions in improving adherence to controller inhaled medication , in children with severe asthma . | OBJECTIVE Determine whether Multisystemic Therapy-Health Care ( MST-HC ) improved asthma knowledge and controller device use skills among African-American youth with poorly controlled asthma and whether any improvements mediated changes in illness management . METHODS A r and omized controlled trial was conducted with 170 adolescents with moderate to severe asthma . Families were r and omized to MST-HC or attention control . Data were collected at baseline and 6 and 12 months after intervention completion . RESULTS In linear mixed models , adolescents in the MST-HC group had increases in asthma knowledge ; asthma knowledge was unchanged for attention control . Controller device use skills increased for adolescents in the MST-HC group , while skills declined for attention control . Both knowledge and skills mediated the relationship between intervention condition and changes in illness management . CONCLUSIONS Tailored , home-based interventions that include knowledge and skills building components are one means by which illness management in African-American youth with poorly controlled asthma can be improved ABSTRACT Objective : To assess the feasibility of a mobile health , inhaled corticosteroid ( ICS ) adherence reminder intervention and to characterize adherence trajectories immediately following severe asthma exacerbation in high-risk urban children with persistent asthma . Methods : Children aged 2–13 with persistent asthma were enrolled in this pilot r and omized controlled trial during an asthma emergency department ( ED ) visit or hospitalization . Intervention arm participants received daily text message reminders for 30 days , and both arms received electronic sensors to measure ICS use . Primary outcomes were feasibility of sensor use and text message acceptability . Secondary outcomes included adherence to prescribed ICS regimen and 30-day adherence trajectories . Group-based trajectory modeling was used to examine adherence trajectories . Results : Forty-one participants ( mean age 5.9 ) were r and omized to intervention ( n = 21 ) or control ( n = 20 ) . Overall , 85 % were Black , 88 % had public insurance , and 51 % of the caregivers had a high school education or less . Thirty-two participant families ( 78 % ) transmitted medication adherence data ; of caregivers who completed the acceptability survey , 25 ( 96 % ) chose to receive daily reminders beyond that study interval . Secondary outcome analyses demonstrated similar average daily adherence between groups ( intervention = 36 % ; control = 32 % , P = 0.73 ) . Three adherence trajectories were identified with none ever exceeding 80 % adherence . Conclusions : Within a high-risk pediatric cohort , electronic monitoring of ICS use and adherence reminders delivered via text message were feasible for most participants , but there was no signal of effect . Adherence trajectories following severe exacerbation were suboptimal , demonstrating an important opportunity for asthma care improvement Real-time medication monitoring ( RTMM ) is a promising tool for improving adherence to inhaled corticosteroids ( ICS ) , but has not been sufficiently tested in children with asthma . We aim ed to study the effects of RTMM with short message service ( SMS ) reminders on adherence to ICS , asthma control , asthma-specific quality of life and asthma exacerbation rate ; and to study the associated cost-effectiveness . In a multicentre , r and omised controlled trial , children ( aged 4–11 years ) using ICS were recruited from five outpatient clinics and were given an RTMM device for 12 months . The intervention group also received tailored SMS reminders , sent only when a dose was at risk of omission . Outcome measures were adherence to ICS ( RTMM data ) , asthma control ( childhood asthma control test question naire ) , quality of life ( paediatric asthma quality of life question naire ) and asthma exacerbations . Costs were calculated from a healthcare and societal perspective . We included 209 children . Mean adherence was higher in the intervention group : 69.3 % versus 57.3 % ( difference 12.0 % , 95 % CI 6.7%–17.7 % ) . No differences were found for asthma control , quality of life or asthma exacerbations . Costs were higher in the intervention group , but this difference was not statistically significant . RTMM with tailored SMS reminders improved adherence to ICS , but not asthma control , quality of life or exacerbations in children using ICS for asthma . e-Monitoring with tailored SMS reminders improves adherence to ICS , but not clinical outcomes in children with asthma BACKGROUND Suboptimum adherence to preventive asthma treatment is associated with substantial morbidity and mortality , yet adherence often remains poor . We aim ed to investigate whether use of an inhaler with audiovisual reminders leads to improved adherence and asthma outcomes in school-aged children who presented to the emergency department with an asthma exacerbation . METHODS We did a r and omised controlled trial in patients aged 6 - 15 years who attended the regional emergency department in Auckl and , New Zeal and with an asthma exacerbation and were on regular inhaled corticosteroids . Using a simple , unrestricted block r and omisation with block sizes of 200 , we r and omly assigned patients to receive an electronic monitoring device for use with their preventer inhaler with the audiovisual reminder functions either enabled to support adherence to inhaled corticosteroids ( intervention group ) or disabled ( control group ) . Participants were followed up every 2 months for 6 months . The primary outcomes were adherence to preventive inhaled corticosteroids and number of days absent from school for any reason . Asthma control was assessed as a secondary outcome . All analyses were done in the intention-to-treat population . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12613001353785 . FINDINGS The study took place between May 10 , 2010 , and Feb 26 , 2012 . We r and omly assigned 220 patients , 110 to the intervention group and 110 to the control group . Median percentage adherence was 84 % ( 10th percentile 54 % , 90th percentile 96 % ) in the intervention group , compared with 30 % ( 8 % , 68 % ) in the control group ( p<0·0001 ) . The proportion of days absent from school for any reason was 1·9 % ( 10th percentile 0·0 % , 90th percentile 7·9 % ) in the intervention group and 1·7 % ( 0·0 % , 8·6 % ) in the control group . The change in asthma morbidity score from baseline to 6 months was significantly greater in the intervention group than in the control group ( p=0·008 ) , with a reduction of 2·0 points from a mean baseline score of 9·3 ( SD 2·2 ) to 7·3 ( 2·1 ) in the intervention group , compared with a reduction of 1·2 points from a baseline of 9·2 ( 2·5 ) to 8·0 ( 2·2 ) in the control group . INTERPRETATION Use of an electronic monitoring device with an audiovisual reminder led to significant improvements in adherence to inhaled corticosteroids in school-aged children with asthma . This intervention could be beneficial for the improvement of asthma control in patients for whom poor asthma control is related to poor adherence . FUNDING Health Research Council of New Zeal and and Cure Kids International guidelines recommend that severe asthma can only be diagnosed after contributory factors , including adherence , have been addressed . Accurate assessment of adherence is difficult in clinical practice . We hypothesised that electronic monitoring in children would identify nonadherence , thus delineating the small number with true severe asthma . Asthmatic children already prescribed inhaled corticosteroids were prospect ively recruited and persistence of adherence assessed using electronic monitoring devices . Spirometry , airway inflammation and asthma control were measured at the start and end of the monitoring period . 93 children ( 62 male ; median age 12.4 years ) were monitored for a median of 92 days . Median ( range ) monitored adherence was 74 % ( 21–99 % ) . We identified four groups : 1 ) good adherence during monitoring with improved control , 24 % ( likely previous poor adherence ) ; 2 ) good adherence with poor control , 18 % ( severe therapy-resistant asthma ) ; 3 ) poor adherence with good control , 26 % ( likely overtreated ) ; and 4 ) poor adherence with poor control , 32 % . No clinical parameter prior to monitoring distinguished these groups . Electronic monitoring is a useful tool for identifying children in whom a step up in treatment is indicated . Different approaches are needed in those who are controlled when adherent or who are nonadherent . Electronic monitoring is essential in a paediatric severe asthma clinic . Children with true , severe therapy-resistant asthma can not be identified without electronic adherence monitoring OBJECTIVE To determine whether a parent-youth teamwork intervention improved medication adherence and related outcomes among youth with asthma . METHODS We used a r and omized clinical trial with 48 youth ( aged 9 - 15 years ) assigned to 1 of 3 groups : Teamwork Intervention ( TI ) , Asthma Education ( AE ) , or St and ard Care ( SC ) . Treatment occurred across 2 months , with a 3-month follow-up assessment . Adherence to inhaled corticosteroids was assessed via the MDILog-II . Parent-adolescent conflict , asthma functional severity , and spirometry assessment s were obtained pre-treatment , post-treatment , and on follow-up . Mixed linear model analysis was used to evaluate group and time effects for outcome measures . RESULTS TI group had significantly higher adherence and lower functional severity scores than AE or SC conditions , and lower parent-reported conflict and a trend for higher spirometry values compared with the SC group . CONCLUSIONS Results suggest support for the efficacy of TI for improving medication adherence as youth acquire more responsibility for their asthma management BACKGROUND Poor adherence to inhaled corticosteroids ( ICS ) is a critical risk factor contributing to asthma morbidity among low-income minority adolescents . OBJECTIVE This trial tested whether peer support group meetings and peer asthma messages delivered via mp3 players improved adherence to ICS . METHODS Low-income African American and /or Hispanic adolescents , ages 11 - 16 years old , with persistent asthma , and poor ( ≤ 48 % ) adherence to prescription ICS during the 3-week run-in were r and omized to intervention or attention control groups ( ATG ) for the 10-week treatment . During treatment , the intervention arm subjects participated in weekly coping peer group support sessions and received mp3 peer-recorded asthma messages that promoted adherence . The ATG participated in weekly meetings with a research assistant and received an equivalent number of mp3 physician-recorded asthma messages . Adherence was measured by using self-report and the Doser CT , an electronic dose counter . The primary outcome was the difference in adherence at 10 weeks between the 2 arms . RESULTS Thirty-four subjects were r and omized to each arm . At 10 weeks , no statistical difference in objective ly measured adherence could be detected between the 2 arms when adjusting for baseline adherence ( P = .929 ) . Adherence declined in both groups over the course of the active treatment period . In both study arms , self-reported adherence by participants was significantly higher than their objective ly measured adherence at week 10 ( P < .0001 ) . CONCLUSION Improving medication adherence in longitudinal studies is challenging . Peer support and mp3-delivered peer asthma messages may not be of sufficient dose to improve outcomes Purpose To investigate the association of ethnicity with objective ly , electronically measured adherence to inhaled corticosteroids ( ICS ) in a multicultural population of children with asthma in the city of Amsterdam . Methods The study was design ed as a prospect i ve , observational multicenter study in which adherence to ICS and potential risk factors for adherence to ICS were measured in a cohort of Moroccan and native Dutch children with asthma . Electronic adherence measurements were performed for 3 months per patient using a Real Time Medication Monitoring ( RTMM ) system . Ethnicity and other potential risk factors , such as socio-economic status , asthma control and parental medication beliefs , were extracted from medical records or parent interviews . The association between adherence and ethnicity was analysed using multivariate linear regression analysis . Results A total of 90 children ( aged 1–11 years ) were included in the study and data of 87 children were used for analysis . Average adherence to ICS was 49.3 % . Native Dutch children showed higher adherence to ICS than Moroccan children ( 55.9 vs. 42.5 % , respectively ; p = 0.044 , univariate analysis ) . After correction for confounders ( > 3 annual visits to the paediatric outpatient clinic , regular use of a spacer during inhalation ) , the final regression model showed that ethnicity was independently associated with adherence ( p = 0.028 ) . Conclusions In our Western European population of inner city children with asthma , poor adherence to ICS was a serious problem , and even somewhat more so in ethnic minorities . Paediatricians involved in asthma treatment should be aware of these cultural differences in medication-taking behaviour , but further studies are needed to eluci date the causal mechanism OBJECTIVE To investigate changes in inhaled corticosteroids adherence , both before and after a scheduled follow-up visit , in young children in a comprehensive asthma management program . STUDY DESIGN One-year prospect i ve follow-up study in 104 asthmatic children ( mean age 4.8 years ) . Adherence to inhaled corticosteroids was assessed using electronic ( Smartinhaler ® ) devices . We assessed changes in adherence before and after clinic visits . A > 10 % increase in adherence in the 3 days preceding a clinic visit was considered to reflect clinical ly relevant white coat adherence ( WCA ) if it exceeded background variation in adherence ( median change > 0 , and increase larger than adherence changes after a clinic visit ) . RESULTS Overall adherence was high ( median 85 % ) . A pre-visit increase in adherence of > 10 % was demonstrated in 17 patients ( 22 % ) , but the median change in adherence around a clinic visit was 0 . There were no significant differences in changes in adherence between the days before or after a visit ( P > 0.2 ) . The median coefficient of variation in adherence was 9 % , and did not significantly differ between children with and without a pre-visit increase in adherence ( P = 0.12 ) . Twelve patients ( 15.4 % ) showed an increase of adherence in the month following a clinic visit ; their overall mean ( SE ) adherence was slightly lower ( 73 % ( 4.6 % ) ) than those without such an increase ( 80 % ( 2.2 % ) , P = 0.054 ) . CONCLUSIONS There was no WCA in children with asthma enrolled in a comprehensive asthma management program with high overall adherence . This suggests that WCA in pediatric chronic conditions primarily occurs against the background of low overall adherence BACKGROUND Controllers are underprescribed for children with asthma , and when they are , adherence is suboptimal . We sought to test whether an interactive website grounded in social cognitive theory can improve the dispensing of controller medications and adherence with them where indicated . METHODS R and omized controlled trial . Parents of eligible patients were r and omized to be prompted to assess their child 's asthma each month for 6 months and receive tailored feedback on controller use and adherence strategies . For the next 6 months , participation in the site was optional . Outcomes were assessed at 6 and 12 months . RESULTS A total of 603 families were enrolled . At baseline , 176 ( 29 % ) children had mild-to-severe persistent asthma , whereas 71 % of children met criteria for mild intermittent asthma . Among patients who should have been on controllers at baseline but were not , there was no statistically significant increase in controller prescriptions at 6 months ( odds ratio [ OR ] 2.85 ; 95 % confidence interval [ 95 % CI ] 0.63 - 14.04 ] , P = .17 ) . There was a trend to improved adherence with controllers among users at 6 months ( OR 1.54 , 95 % CI 0.90 - 2.63 , P = .10 ) . Among patients who used controller medicine at both baseline and at 6 months , users in the intervention arm had significantly greater adherence than those in control arm at 6 months ( OR 1.92 ; 95 % CI 1.05 - 3.55 ; P = .02 ) . For patients with persistent asthma at baseline and who were on controller medicine at both time points , patients in the intervention arm had significantly better adherence than those in the control arm at 6 months ( OR 3.33 ; 95 % CI 1.20 - 10.07 , P = .01 ) . However , there were no discernible differences at the 12-month assessment . CONCLUSION A tailored interactive website shows some benefit in improving controller medication adherence during a period of active intervention There are only a few studies assessing the relationship between adherence rate to ICS , as assessed by electronic monitoring , and the level of asthma control in childhood . The present study was carried out to examine the relationship between adherence to beclomethasone diproprionate ( BDP ) as well as other factors related to poor asthma control . In this prospect i ve cohort study , 102 steroid naïve r and omly selected subjects with persistent asthma , aged 5 - 14 years were prescribed 500 - 750 μg daily of BDP-CFC and followed during one year . Adherence to BDP was measured electronically in the 4th , 8th and 12th months of study . The level of asthma control was classified as either controlled or uncontrolled instead of the current three categories recommended by the Global Initiative for Asthma ( GINA ) . Mean adherence rate was higher in patients with controlled asthma during follow-up , but went down from 60.4 % in the 4th month to 49.8 % in the 12th month ( p = 0.038 ) . Conversely , among patients with uncontrolled asthma , the mean adherence rate decreased from 43.8 % to 31.2 % ( p = 0.001 ) . Multivariate analysis showed that the level of asthma control was independently associated to the adherence rate in all follow-up visits ( p-values equal or lower than 0.005 ) . The level of asthma control was directly proportional to adherence rate . Our results suggest that a BDP daily dose by 300 μg seems to be enough to attain control over mild and moderate persistent asthma , including exercise induced asthma |
10,344 | 24,838,729 | We were unable to combine data for other outcomes and individual study results were inconclusive in terms of any effect on depressive symptoms , confidence or partner satisfaction .
AUTHORS ' CONCLUSIONS The findings of this review support the use of parenting programmes to improve the short-term psychosocial wellbeing of parents . | BACKGROUND Parental psychosocial health can have a significant effect on the parent-child relationship , with consequences for the later psychological health of the child .
Parenting programmes have been shown to have an impact on the emotional and behavioural adjustment of children , but there have been no review s to date of their impact on parental psychosocial wellbeing .
OBJECTIVES To address whether group-based parenting programmes are effective in improving parental psychosocial wellbeing ( for example , anxiety , depression , guilt , confidence ) . | Background Approximately 20 % of children experience internalizing or externalizing DSM-IV-TR disorders . This prevalence rate can not be reduced through treatment only . Effective preventive interventions are therefore urgently needed . The aim of the current investigation is to evaluate the two-year efficacy of the group Triple P parenting program administered universally for the prevention of child behavior problems . Methods Based on their respective preschool , N = 280 families were r and omly assigned either to the parent training or to the control group . The efficacy was analyzed using multi- source assessment s , including question naires by mother and father , behavioral observation of mother-child interaction , and teacher evaluations . Results At the 2-year follow-up , both parents in the Triple P intervention reported significant reductions in dysfunctional parenting behavior , and mothers also an increase in positive parenting behavior . In addition , mothers reported significant reductions in internalizing and externalizing child behavior . Single-parent mothers in the Triple P intervention did not report significant changes in parenting or child problem behavior which is primarily due to inexplicable high positive effects in single parent mothers of the control group . Neither mother-child interactions nor teacher ratings yielded significant results . Conclusions The results support the long-term efficacy of the Triple P - group program as a universal prevention intervention for changing parenting behavior in two-parent households , but not necessarily in single-parent mothers The efficacy of group parent training was assessed in improving compliance and time on task in preschoolers with attention-deficit disorder with hyperactivity . Positive effects were obtained on measures of child compliance , but not on measures of attention . Parental compliance-management skills and overall style of interaction were also positively affected . The use of parent training for early intervention with ADDH children is discussed OBJECTIVE This study examined the effects of the Webster-Stratton parenting program on the parenting skills of maltreating mothers and on the autonomy of their children ( 3 - 8 years ) . METHOD A r and omized controlled trial was used . Twenty-six maltreating families were r and omly assigned to one of two conditions : the 16-hour weekly intervention group , or the 4-month wait list control group . Pre- and post-intervention independent assessment s included a 2-hour home visit involving videotaped mother-child interactions during two prescribed , 10-minute play activities . RESULTS Compared to the control group , treatment mothers demonstrated significant improvement in involvement and marginally significant improvement in autonomy-support , but no improvement in structure . Treatment group children showed no significant improvement in autonomy when compared to control group children . CONCLUSIONS This parenting program proved effective with maltreating parents . The lack of demonstrated effect on children may reflect the need for a larger and more sustained treatment dose and /or the need to include parent-child interaction opportunities in the program . At the same time , while treatment gains were limited to the parent , the high treatment adherence rate ( 92 % attended six or more of the eight program sessions ) and low attrition rate ( n=1 ) indicate that the treatment gains may hold potential for more thorough examination The long-term effect of two parent training programs for conduct problem preschoolers is reported . Families of 54 behaviorally disturbed preschool-aged children were r and omly assigned to 1 of 3 treatment conditions : st and ard Parent – Child Interaction Therapy ( STD ) , an abbreviated form of PCIT ( ABB ) , and a no-treatment waitlist control group ( WL ) . Of the families who completed treatment ( STD and ABB ) , data were collected on 97 % and 94 % of families at 1- and 2-year follow-up , respectively . Follow-up assessment of parent report and independent observations indicated that treatment gains were largely maintained for both treatment conditions with little difference between the two treatments . The findings suggest that an abbreviated form of PCIT has long-term benefits for families with young children displaying early conduct problems Objective To present the design , methods , and rationale of the Child/Adolescent Anxiety Multimodal Study ( CAMS ) , a recently completed federally-funded , multi-site , r and omized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy ( CBT ) , sertraline ( SRT ) , and their combination ( COMB ) against pill placebo ( PBO ) for the treatment of separation anxiety disorder ( SAD ) , generalized anxiety disorder ( GAD ) and social phobia ( SoP ) in children and adolescents . Methods Following a brief review of the acute outcomes of the CAMS trial , as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders , the design and methods of the CAMS trial are described . Results CAMS was a six-year , six-site , r and omized controlled trial . Four hundred eighty-eight ( N = 488 ) children and adolescents ( ages 7 - 17 years ) with DSM-IV-TR diagnoses of SAD , GAD , or SoP were r and omly assigned to one of four treatment conditions : CBT , SRT , COMB , or PBO . Assessment s of anxiety symptoms , safety , and functional outcomes , as well as putative mediators and moderators of treatment response were completed in a multi-measure , multi-informant fashion . Manual-based therapies , trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity . A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial , study protocol s and quality assurance . Conclusions CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls . CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidence d-based psychosocial ( CBT ) and pharmacologic ( SSRI ) treatments to date for the most commonly occurring pediatric anxiety disorders . Primary and secondary results of CAMS will hold important implication s for informing practice -relevant decisions regarding the initial treatment of youth with anxiety disorders . Trial registration Clinical Trials.gov NCT00052078 BACKGROUND Despite a wealth of evidence showing that behavioural family intervention is an effective intervention for parents of children with behavioural and emotional problems , little attention has been given to the relationship between parents functioning at work and their capacity to manage parenting and other home responsibilities . This study evaluated the effects of a group version of the Triple-P Positive Parenting Program ( WPTP ) design ed specifically for delivery in the workplace . METHOD Participants were 42 general and academic staff from a major metropolitan university who were reporting difficulties managing home and work responsibilities and behavioural difficulties with their children . Participants were r and omly assigned to WPTP , or to a waitlist control ( WL ) condition . RESULTS Following intervention , parents in WPTP reported significantly lower levels of disruptive child behaviour , dysfunctional parenting practice s , and higher levels of parental self-efficacy in managing both home and work responsibilities , than parents in the WL condition . These short-term improvements were maintained at 4-months follow-up . There were also additional improvements in reported levels of work stress and parental distress at follow-up in the WPTP group compared to post-intervention . CONCLUSIONS Implication s for the development of ' family-friendly ' work environments and the prevention of child behaviour problems are discussed BACKGROUND There is a pressing need for cost-effective population -based interventions to tackle early-onset antisocial behaviour . As this is determined by many factors , it would seem logical to devise interventions that address several influences while using an efficient means of delivery . The aim of this trial was to change four risk factors that predict poor outcome : ineffective parenting , conduct problems , attention deficit/hyperactivity disorder ( ADHD ) symptoms , and low reading ability . METHODS A r and omised controlled trial was carried out in eight schools in London , Engl and . Nine hundred and thirty-six ( 936 ) 6-year-old children were screened for antisocial behaviour , then parents of 112 high scorers were r and omised to parenting groups held in schools or control ; 109 were followed up a year later . The intervention lasted 28 weeks and was novel as it had components to address both child behaviour ( through the Incredible Years programme ) and child literacy ( through a new ' SPOKES ' programme to help parents read with their children ) . Fidelity of implementation was emphasised by careful training of therapists and weekly supervision . Controls received an information helpline . Assessment of conduct problems was by parent interview , parenting by direct observation and child reading by psychometric testing . RESULTS At follow-up parents allocated to the intervention used play , praise and rewards , and time out more often than controls , and harsh discipline less ; effect sizes ranged from .31 to .59 sd ( p-values .046 to .005 ) . Compared to control children , whose behaviour did n't change , intervention children 's conduct problems reduced by .52sd , ( p < .001 ) , dropping from the 80th to the 61st percentile ; oppositional-defiant disorder ( ODD ) halved from 60 % to 31 % ( p = .003 ) . ADHD symptoms reduced by .44sd ( p = .002 ) , and reading age improved by six months ( .36sd , p = .027 ) . Teacher-rated behaviour did n't change . The programme cost pound2,380 ( $ 3,800 ) per child . CONCLUSIONS Effective population -based early intervention to improve the functioning of with antisocial behaviour is practically feasible by targeting multiple risk factors and emphasising implementation fidelity BACKGROUND Controlling , uninvolved , and rejecting parenting in early childhood are strong predictors of later disruptive behavior disorders . However , there have been no evaluations of non-targeted groups for parents of very young children , despite their potential advantages . METHODS We r and omly assigned 79 mothers of 12- to 36-month-olds to an 8-session parent training program ( called ' COPEing with Toddler Behaviour ' ) or to a waiting list control condition . We investigated the immediate and short-term impact on parent-reported child behavior problems , observed parent-child interaction , and self-reported parenting behavior and parent functioning . RESULTS In an intent-to-treat design , the program yielded significant effects on child behavior problems , positive parent-child interaction , and parental overreactivity and depression but not observed negative child behavior or parental laxness . Most effects were significant at both post-test and 1-month follow-up and effects sizes were small to medium for the intervention group and inverse to small for the control group . CONCLUSIONS The potential of the program to prevent later behavior problems is supported by improvements in six of the eight outcomes . As part of a community strategy , groups such as COPEing with Toddler Behaviour may promote positive parent-child interaction and children 's mental health The purpose of this study was to evaluate the effectiveness of a 2-component intervention for biological and foster parent ( pairs ) to improve parenting practice s , co-parenting , and child externalizing problems . Participants were biological and foster parents ( N=128 ) of primarily neglected children ( ages 3 to 10 years ) placed in regular foster homes . Biological and foster parents were r and omly assigned in pairs to the intervention ( n=80 ) or a usual care ( n=48 ) condition . Intervention families received a 12-week parenting course ( Incredible Years ) and a newly developed co-parenting component . Key findings included significant gains in positive parenting and collaborative co-parenting for both biological and foster parents at the end of the intervention . At follow-up , intervention parents sustained greater improvement in positive parenting , showed gains in clear expectations , and reported a trend for fewer child externalizing problems . Findings supported the feasibility of offering joint parenting training to meet the needs of participating families and demonstrated that the co-parenting construct applied to families in the foster care system was amenable to intervention This paper examined the effects of a parenting intervention targeting working parents called Workplace Triple P. The intervention targeted both parenting and work factors , focusing on key transition times ( e.g. , from home to work ) and trained parents to more effectively manage these transitions . One-hundred- and -twenty-one working parents with children ranging in age from 1 - 16 years were r and omly assigned to either a Workplace Triple P condition ( WPTP ) or to a waitlist control condition ( WLC ) . Results showed that parents who had received the intervention reported significantly lower levels on measures of personal distress and dysfunctional parenting ; and higher levels of work commitment , work satisfaction , and self-efficacy . Implication s for the delivery of parenting interventions as employee assistance programs are discussed along with how such interventions can enhance work and family life A pilot trial provided some evidence that the Triple P Positive Parenting Program is effective with and acceptable to a Japanese population in Australia ( Matsumoto , Sofronoff , & S and ers , 2007 ) . This effectiveness study aim ed to address theoretical and practical concerns related to the parent training program in community setting s in Japan . The research used community re sources within an ecological framework . Fifty-four Japanese families living in a Tokyo metropolitan area were r and omly assigned to either a treatment or a wait-list control group . Program effects and acceptability were examined and then compared with the outcomes from the trial with Japanese parents living in Australia . The results showed significant program effects and high levels of acceptability of the program and core parenting skills , which was consistent with the pilot trial . The findings provided support for the effectiveness and sociocultural validation of Triple P in Japanese society . Intervention effects and program acceptability as well as limitations and future research are discussed Aims : To assess the effectiveness of a parenting programme , delivered by health visitors in primary care , in improving the mental health of children and their parents among a representative general practice population . Methods : Parents of children aged 2–8 years who scored in the upper 50 % on a behaviour inventory were r and omised to the Webster-Stratton 10 week parenting programme delivered by trained health visitors , or no intervention . Main outcome measures were the Eyberg Child Behaviour Inventory and the Goodman Strengths and Difficulties Question naire to measure child behaviour , and the General Health Question naire , Abidin ’s Parenting Stress Index , and Rosenberg ’s Self Esteem Scale to measure parents ’ mental health . These outcomes were measured before and immediately after the intervention , and at six months follow up . Results : The intervention was more effective at improving some aspects of the children ’s mental health , notably conduct problems , than the no intervention control condition . The Goodman conduct problem score was reduced at immediate and six month follow up , and the Eyberg Child Behaviour Inventory was reduced at six months . The intervention also had a short term impact on social dysfunction among parents . These benefits were seen among families with children scoring in the clinical range for behaviour problems and also among children scoring in the non- clinical ( normal ) range . Conclusion : This intervention could make a useful contribution to the prevention of child behaviour problems and to mental health promotion in primary care This study evaluated the relative efficacy of two promising treatments of child abuse and child ne-glect : parent training and multisystemic therapy . Subjects included 18 abusive families and 15 ne-glectful families who were r and omly assigned to the treatment conditions . Self-report and observa-tional measures were used to evaluate the effects of treatment at three levels that have been associatedwith child maltreatment : individual functioning , family relations , and stress/social support . Statisti-cal analyses revealed that families who received either treatment showed decreased parental psychiat-ric symptomology , reduced overall stress , and a reduction in the severity of identified problems . Analyses of sequential observational measures revealed that multisystemic therapy was more effec-tive than parent training at restructuring parent-child relations . Parent training was more effectivethan multisystemic therapy at reducing identified social problems . The differentia ] inOuences of thetwo treatments were probably associated with differences in their respective treatment context s and epistemologies BACKGROUND Programmes that promote early psychological development of children in the developed world have been found to be beneficial . However , such programmes are rare in underprivileged parts of the developing world . We adapted one such parent-based programme ( Learning Through Play ) for a rural Pakistani population and aim ed to study if : ( 1 ) it was acceptable to community health workers ; ( 2 ) the programme led to an improvement , after a period of 6 months , in mothers ' knowledge and attitudes about early infant development ; ( 3 ) it led to a reduction in the levels of maternal mental distress in the post-natal period . METHODS Using a cluster r and omized design with villages as unit of r and omization , 163 mothers from 24 villages in a rural sub-district of Rawalpindi , Pakistan , received the ' Learning Through Play ' programme , whereas 146 mothers from 24 villages acted as controls . Twenty-four community health workers were trained to carry out the programme . Assessment s were conducted using a specially developed 15-item Infant Development Question naire and the 20-item Self-Reporting Question naire ( SRQ ) . RESULTS Over 80 % of the community health workers trained found the programme to be relevant and were able to integrate it into their routine work . There was a significant increase in mothers ' knowledge and positive attitudes about infant development in the intervention group , compared with the control group . Women in the intervention group answered correctly 4.3 ( 95 % CI 3.7 - 14.9 , P < 0.001 ) more questions than the control group . There was no difference in levels of mental distress measured by the SRQ . CONCLUSIONS The ' Learning Through Play ' programme was successfully integrated into the existing health system and accepted by community health workers . The programme succeeded in improving the knowledge and attitudes of mothers about infant development This study was a r and omized control trial ( RCT ) of Parent Management Training -- The Oregon Model ( PMTO ) in Norway . A sample representing all health regions of Norway and consisting of 112 children with conduct problems and their families participated in the study . Families were r and omly assigned to either PMTO or a regular services comparison group . PMTO was delivered via existing children 's services , and families were recruited using the agencies ' regular referral procedures , making this the first effectiveness study of PMTO and the first RCT of PMTO conducted outside of the United States . Using a multiagent-multi method approach , results showed that PMTO was effective in reducing parent-reported child externalizing problems , improving teacher-reported social competence , and enhancing parental discipline . Age level and gender modified the effects of PMTO treatment on other outcomes . In a path model , participation in PMTO was associated with improved parental discipline , and effective discipline predicted greater child compliance , fewer child-initiated negative chains , and lower levels of child externalizing problems . Findings are presented along with a discussion of the implication s for practice and research and the challenges accompanying effectiveness trials Background Considering the high burden of disease of psychosocial problems in children and adolescents , early intervention regarding problem behaviour of young children is very important . The Preventive Child Healthcare ( PCH ) offers a good setting to detect such problem behaviour and to provide parenting support to the parents concerned . This paper aims to describe the design of an effectiveness study of a parenting programme for parents of children with mild psychosocial problems after an initial , evidence based screening in routine PCH . Methods / Design The effects of the intervention will be studied in a r and omised controlled trial . Prior to a routine PCH health examination , parents complete a screening question naire on psychosocial problems . Parents of children with increased but still sub clinical levels of psychosocial problems will be assigned at r and om to the experimental group ( Triple P , level 3 ) or to the control group ( care as usual ) . Outcome measures , such as problem behaviour in the child and parenting behaviour , will be assessed before , directly after and 6 and 12 months after the intervention . Discussion Parenting support may be an effective intervention to reduce psychosocial problems in children but evidence -based parenting programmes that fit the needs of the PCH are not available as yet . Although the Triple P programme seems promising and suitable for a universal population approach , evidence on its effectiveness in routine PCH still lacks . Trial registration This study evaluated the effects of problem-solving skills training ( PSST ) and parent management training ( PMT ) on children ( N = 97 , ages 7 - 13 years ) referred for severe antisocial behavior . Children and families were assigned r and omly to 1 of 3 conditions : PSST , PMT , or PSST and PMT combined . It was predicted that ( a ) each treatment would improve child functioning ( reduce overall deviance and aggressive , antisocial , and delinquent behavior , and increase prosocial competence ) ; and ( b ) PSST and PMT combined would lead to more marked , pervasive , and durable changes in child functioning and greater changes in parent functioning ( parental stress , depression , and overall symptoms ) . Expectations were supported by results at posttreatment and 1-year follow-up . PSST and PMT combined led to more marked changes in child and parent functioning and placed a greater proportion of youth within the range of nonclinic ( normative ) levels of functioning OBJECTIVE Despite recognition of the need for parenting interventions to prevent childhood behavioral problems , few community programs have been evaluated . This report describes the r and omized controlled evaluation of a four-session psychoeducational group for parents of preschoolers with behavior problems , delivered in community agencies . METHOD In 1998 , 222 primary caregivers , recruited through community ads , filled out question naires on parenting practice s and child behavior . Parents were r and omly assigned to immediate intervention or a wait-list control . The intervention comprised three weekly group sessions and a 1-month booster , the focus being to support effective discipline ( using the video 1 - 2 - 3 Magic ) and to reduce parent-child conflict . RESULTS Using an intent-to-treat analysis , repeated- measures analyses of variance indicated that the parents who received the intervention reported significantly greater improvement in parenting practice s and a significantly greater reduction in child problem behavior than the control group . The gains in positive parenting behaviors were maintained at 1-year follow-up in a subset of the experimental group . CONCLUSIONS This brief intervention program may be a useful first intervention for parents of young children with behavior problems , as it seems both acceptable and reasonably effective Behavioral parent training is an efficacious treatment for attention-deficit/hyperactivity disorder ( ADHD ) . However , single-mother households are at high risk for poor outcomes during and following behavioral parent training . This study r and omly assigned cohorts of 120 single mothers of children ( ages 5–12 years ) with ADHD to a waitlist control group , a traditional behavioral parent training program , or an enhanced behavioral parent training program — the Strategies to Enhance Positive Parenting ( STEPP ) program . Intent-to-treat analysis demonstrated benefits of participating in behavioral parent training , in general , and the STEPP program more specifically at immediate posttreatment on child and parental functioning . Moreover , the STEPP program result ed in increased engagement to treatment . However , results indicated that behavioral parent training does not normalize behavior for most children and treatment gains are not maintained OBJECTIVE To test a theoretical model examining processes through which a parent-focused educational-behavioral intervention [ Creating Opportunities for Parent Empowerment ( COPE ) ] relates to children 's post-hospital adjustment problems . METHODS Mothers ( n = 143 ) and their 2 - 7-year-old children , unexpectedly hospitalized in two pediatric intensive care units , were r and omized to COPE or control conditions . Maternal measures included parental beliefs , anxiety , negative mood , and child adjustment 3 months post discharge . Observers rated maternal support of their children during hospitalization . RESULTS Structural equation modeling suggested that the model tested provided a reasonable fit to the data [ chi2 ( 97 df ) = 129.43 ; p = .016 ; root mean square error of approximation = .048 ; comparative fit index = .95 ] . COPE effects on children 's post-hospital externalizing behaviors were indirect , via associations with parental beliefs and maternal negative mood state . Furthermore , COPE participation was associated with more maternal support of their children , which was also associated with less internalizing and externalizing behaviors 3 months post discharge . CONCLUSION Implementing COPE may help avert future mental health problems in this high risk population . Underst and ing the processes by which an already empirically vali date d program relates to child outcomes is likely to aid clinicians and administrators in the widespread uptake of the COPE program Objective : This study assessed the feasibility and efficacy of a parent-education group for families with young children and a parent with depression . We design ed the program to be readily disseminated if shown to be effective . Method : We recruited 44 parents with depression from clinics and family doctors in Hamilton , Ontario , and r and omly assigned them to receive the parenting program or to a wait-list control group . The outcomes measured included knowledge of depression , parenting , family relationships , depression symptoms , child depressive symptoms , and functioning . We used analysis of covariance to test for posttreatment differences between experimental and control groups . Results : Of the treatment group , 27 % dropped out at posttreatment , and 43 % by follow-up . Those who dropped out had more severe depression at baseline than did those who completed the program , and there was selective loss of parents with more severe depression in the experimental group . In intention-to-treat analyses at posttreatment , prob and s in the experimental group reported more improvements on family functioning , parenting sense of competence , and family and parent conflict than did control subjects . St and ardized effect sizes ( ES ) were medium ( 0.4 to 0.6 ) . When baseline depressive symptom scores were controlled in the analyses , the between-group differences were reduced , showing that selective loss of participants may have influenced the findings . Conclusions : On balance , the results are encouraging and support the further development and evaluation of the group intervention . However , the study does not provide unequivocal evidence in support of the program . Before it is transferred to other setting s , the program needs further modification to improve participation by parents with more severe depression and further evaluation of its effectiveness A r and omized experimental test of the implementation feasibility and the efficacy of a culturally adapted Parent Management Training intervention was conducted with a sample of 73 Spanish-speaking Latino parents with middle-school-aged youth at risk for problem behaviors . Intervention feasibility was evaluated through weekly parent satisfaction ratings , intervention participation and attendance , and overall program satisfaction . Intervention effects were evaluated by examining changes in parenting and youth adjustment for the intervention and control groups between baseline and intervention termination approximately 5 months later . Findings provided strong evidence for the feasibility of delivering the intervention in a larger community context . The intervention produced benefits in both parenting outcomes ( i.e. , general parenting , skill encouragement , overall effective parenting ) and youth outcomes ( i.e. , aggression , externalizing , likelihood of smoking and use of alcohol , marijuana , and other drugs ) . Differential effects of the intervention were based on youth nativity status The present study evaluated the effectiveness of the Positive Parenting Program ( Triple P ) with a sample of Chinese parents of children with early onset conduct-related problems in Hong Kong . The participants consisted of 91 parents whose children attended maternal and child health centers and child assessment centers for service , and were between three to seven years old . Participants were r and omly assigned to the intervention ( TP ) and a waitlist control group ( WL ) . There was no significant difference in pre-intervention measures between the two groups . However , at post intervention , participants in the TP group reported significantly lower levels of child behavior problems , lower dysfunctional parenting styles , and higher parent sense of competence , compared to the WL group . Implication s of these findings for the use of Triple P with families of Chinese descent are discussed OBJECTIVE To evaluate two different parent-based therapies for preschool attention-deficit/hyperactivity disorder ( ADHD ) in a community sample . METHOD Three-year-old children displaying a preschool equivalent of ADHD ( n = 78 ) were r and omly assigned to either a parent training ( PT ; n = 30 ) , a parent counseling and support ( PCO&S ; n = 28 ) , or a waiting-list control group ( n = 20 ) . The PT group received coaching in child management techniques . The PC&S group received nondirective support and counseling . Measures of child symptoms and mothers ' well-being were taken before and after intervention and at 15 weeks follow-up . RESULTS ADHD symptoms were reduced ( F2,74 = 11.64 ; p < .0001 ) and mothers ' sense of well-being was increased by PT relative to both other groups ( F2,74 = 10.32 ; p < .005 ) . Fifty-three percent of children in the PT group displayed clinical ly significant improvement ( chi 2 = 4.08 ; p = .048 ) . CONCLUSIONS PT is a valuable treatment for preschool ADHD . PC&S had little effect on children 's behavior . Constructive training in parenting strategies is an important element in the success of parent-based interventions . Psychostimulants are not a necessary component of effective treatment for many children with preschool ADHD Objective To assess the efficacy of an intervention design ed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances . Design R and omised controlled trial . Setting Khayelitsha , a peri-urban settlement in South Africa . Participants 449 pregnant women . Interventions The intervention was delivered from late pregnancy and for six months postpartum . Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting . The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother . Women in the control group received no therapeutic input from the research team . Main outcome measures Primary outcomes : quality of mother-infant interactions at six and 12 months postpartum ; infant attachment security at 18 months . Secondary outcome : maternal depression at six and 12 months . Results The intervention was associated with significant benefit to the mother-infant relationship . At both six and 12 months , compared with control mothers , mothers in the intervention group were significantly more sensitive ( 6 months : mean difference=0.77 ( SD 0.37 ) , t=2.10 , P<0.05 , d=0.24 ; 12 months : mean difference=0.42 ( 0.18 ) , t=−2.04 , P<0.05 , d=0.26 ) and less intrusive ( 6 months : mean difference=0.68 ( 0.36 ) , t=2.28 , P<0.05 , d=0.26 ; 12 months : mean difference=−1.76 ( 0.86 ) , t=2.28 , P<0.05 , d=0.24 ) in their interactions with their infants . The intervention was also associated with a higher rate of secure infant attachments at 18 months ( 116/156 ( 74 % ) v 102/162 ( 63 % ) ; Wald=4.74 , odds ratio=1.70 , P<0.05 ) . Although the prevalence of maternal depressive disorder was not significantly reduced , the intervention had a benefit in terms of maternal depressed mood at six months ( z=2.05 , P=0.04 ) on the Edinburgh postnatal depression scale ) . Conclusions The intervention , delivered by local lay women , had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment , factors known to predict favourable child development . If these effects persist , and if they are replicated , this intervention holds considerable promise for use in the developing world . Trial registration Current Controlled Trials IS RCT N25664149 Aims : To test the effectiveness at one year of the Webster Stratton Parents and Children Series group parenting programme in a population sample of parents . Methods : In a multicentre block r and omised controlled trial , parents of children aged 2–8 years in 116 families who scored in the upper 50 % on a vali date d behaviour inventory , took part in Webster-Stratton ’s 10 week parenting programme led by trained and supervised health visitors . The following outcome measures were used : Eyberg Child Behaviour Inventory , Goodman Strengths and Difficulties Question naire , General Health Question naire , Parenting Stress Index , Rosenberg Self Esteem Scale . Results : The intervention significantly reduced child behaviour problems and improved mental health at immediate and 6 month follow ups . One year differences between control and intervention groups were not significant . Qualitative results suggest that these findings might be attributable in part to either Hawthorne effects or contamination of control group . At interview parents described ways in which the programme had improved their mental health . They reported gains in confidence and feeling less stressed . Some also reported beneficial changes in their own and their children ’s behaviour and improved relationships with their children . Some spoke of a need for further sessions to support the behaviour changes they had managed to make , and some the desire for attendance by both parents . Conclusions : Parenting programmes have the potential to promote mental health and reduce social inequalities , but further work is needed to improve long term effectiveness Head Start centers were r and omly assigned to intervention ( parent training ) or control conditions , and the role of maternal mental health risk factors on participation in and benefit from parent training was examined . Parenting was measured by parent report and independent observation in 3 domains : harsh/negative , supportive/positive , inconsistent/ineffective parenting . Structural equation modeling showed that parent engagement training was associated with improved parenting in a dose-response fashion . Mothers with mental health risk factors ( i.e. , depression , anger , history of abuse as a child , and substance abuse ) exhibited poorer parenting than mothers without these risk factors . However , mothers with risk factors were engaged in and benefited from the parenting training program at levels that were comparable to mothers without these risk factors This study evaluated two variants of a behavioral parent training program known as Stepping Stones Triple P ( SSTP ) using 74 preschool-aged children with developmental disabilities . Families were r and omly allocated to an enhanced parent training intervention that combined parenting skills and care-giving coping skills ( SSTP-E ) , st and ard parent training intervention alone ( SSTP-S ) or waitlist control ( WL ) condition . At post-intervention , both programs were associated with lower levels of observed negative child behavior , reductions in the number of care-giving setting s where children displayed problem behavior , and improved parental competence and satisfaction in the parenting role as compared with the waitlist condition . Gains attained at post-intervention were maintained at 1-year follow-up . Both interventions produced significant reductions in child problem behavior , with 67 % of children in the SSTP-E and 77 % of children in the SSTP-S showing clinical ly reliable change from pre-intervention to follow-up . Parents reported a high level of satisfaction with both interventions Parents of 114 conduct-problem children , aged 3 - 8 years , were r and omly assigned to one of four groups : an individually administered videotape modeling treatment ( IVM ) , a group discussion videotape modeling treatment ( GDVM ) . a group discussion treatment ( GD ) , and a waiting-list control group . Compared ~4th the control group , all three treatment groups of mothers reported significantly fewer child behavior problems , more prosocial behaviors , and less spanking . Fathers in the GDVM and IVM conditions and teachers of children whose parents were in the GDVM and GD conditions also reported significant reductions in behavior problems compared ~4th control subjects . Home visit data indicated that all treatment groups of mothers , fathers , and children exhibited significant behavioral changes . There were relatively few differences between treatment groups on most outcome measures , although the differences found consistently favored the GDVM treatment . However , cost effectiveness was the major advantage of the IVM treatment The Early Head Start Research and Evaluation Project , a r and om-assignment evaluation , found a broad pattern of positive impacts for children and families . However , there were no program impacts on depression or use of mental health services by the time children reached age 3 , at the end of the Early Head Start ( EHS ) program . This paper presents recent findings from the follow-up study in the spring prior to the children entering kindergarten , when a positive program impact emerged for reducing maternal depression . Results show that earlier program impacts on children and parents ( when children were 2 and 3 years of age ) mediated , or led to , the delayed impact on maternal depression . The combination of the most promising child factors accounted for over 57 % of the later impact on depression , while the most promising parent factors accounted for over 35 % of the later impact on depression . Implication s for EHS programs are discussed The authors tested a 12-week parent training program with parents ( n = 208 ) and teachers ( n = 77 ) of 2 - 3-year-olds in day care centers serving low-income families of color in Chicago . Eleven centers were r and omly assigned to 1 of 4 conditions : ( a ) parent and teacher training ( PT + TT ) , ( b ) parent training ( PT ) , ( c ) teacher training ( TT ) , and ( d ) waiting list control ( C ) . After controlling for parent stress , PT and PT + TT parents reported higher self-efficacy and less coercive discipline and were observed to have more positive behaviors than C and TT parents . Among toddlers in high-risk behavior problem groups , toddlers in the experimental conditions showed greater improvement than controls . Most effects were retained 1 year later . Benefits were greatest when parents directly received training BACKGROUND One in ten women suffers from postnatal depression ( PND ) and their children have elevated rates of psychopathology . We compared caseness of PND using the Edinburgh Postnatal Depression Scale ( EPDS ) , the most commonly used research tool for the detection of PND , and the Clinical Interview Schedule ( CIS ) in terms of their relative abilities to identify infants at risk of psychopathology in middle childhood . METHOD In a prospect i ve longitudinal primary care study , 147 r and omly selected women were administered both the CIS and the EPDS at three months postpartum . Childhood psychopathology was identified by face-to-face interview at 11 years . RESULTS The risk for psychiatric disorder at 11 years was four times greater among children whose mothers were cases of PND on the CIS , compared to children whose mothers were not depressed . Using the EPDS to identify PND , there was no significant difference in the risk for children whose mothers scored above and below a conventional cut-off score . LIMITATIONS This study was retrospectively design ed and was not part of the original study plan . CONCLUSIONS These data support the evidence that accurate detection of PND is better achieved by face-to-face clinical interview than through the use of the EPDS . They provide novel evidence that a simple diagnostic clinical interview for PND , in contrast to the EPDS , can identify mothers whose children will be at an increased risk of developing psychiatric disorder in later childhood This study provides evidence of the effectiveness of behaviorally based parenting skills classes provided by carefully trained and supervised group leaders who were not mental health clinicians . A program for parents of at-risk middle school students was evaluated in a r and omized controlled trial in 8 small Oregon communities . Parents ( N = 303 ) were r and omly assigned to immediate treatment or a wait-list condition . Data were analyzed using latent growth modeling . Participation in the program led to significant improvements in problem-solving interactions as indicated by parent reports and a Taped Situations Test . Parents ' over-reactivity and laxness toward their children 's behavior were reduced and their feelings toward their children improved significantly as a function of treatment . Parent-reported child antisocial behavior was also reduced In a r and omized prevention trial , 238 recently separated mothers and their young sons were assigned to either Parent Management Training ( PMT ) or a comparison group . Families were intensively assessed at baseline and at each 6-month interval through 30 months . To underst and the effects of PMT , we first evaluated effect sizes among family variables over time . Second , because observed parenting was the target of PMT , we hypothesized a sequential pattern of structured changes within and between individuals . Using constructs with mismatched sources of data , we conducted a set of latent growth mediational analyses to test hypothesized mechanisms explaining change . Effect sizes indicated that parenting changed first within 12 months , followed by changes in boy behaviors and finally changes in maternal depression within 30 months . Unique follow-up findings indicated that intervention effects on reductions in maternal depression were mediated by reductions in boy externalizing ; intervention effects on externalizing were mediated by reductions in boy depression . As expected , increases in effective parenting predicted reductions in child behavior problems . PMT effects on internalizing were direct and indirect , partially mediated by parenting practice s. Results are discussed from a system 's perspective on PMT amplifiers Child physical abuse is recognized as a major public health problem that affects children and is likely to become increasingly common . The objective of this study was to examine the effects of a cognitive adjustment program on parental attitudes toward child rearing and the potential for this abuse . Child-care centers were r and omly allocated to either the intervention or the control group . The sample included 116 Thai parents of children aged 1 - 6 years . The intervention group attended the cognitive adjustment program while the control group received the usual services . The results showed that , after program completion , the intervention group had statistically significantly better parental attitudes toward child rearing , but not a significantly lower potential for CPA than the control group . We concluded that the cognitive adjustment program was effective in altering parental attitudes toward child rearing . However , in order to enhance its efficacy , the program should be modified to be more intensive and it should be studied further for its effect on the potential for abuse Two family therapies were compared using teens with attention-deficit/hyperactivity disorder . Ninety-seven families were assigned to either 18 sessions of problem-solving communication training ( PSCT ) alone or behavior management training ( BMT ) for 9 sessions followed by PSCT for 9 sessions ( BMT/PSCT ) . Both treatments demonstrated significant improvement in ratings of parent-teen conflicts at the midpoint but did not differ . By posttreatment , both produced improvement on ratings and observations but did not differ . Significantly more families dropped out of PSCT alone than out of BMT/PSCT . At most , 23 % of families showed reliable change either by midpoint or by posttreatment , with no differences between therapies . Yet 31%-70 % of families were normalized . Group-level change and normalization rates support treatment efficacy , whereas indices of reliable change are less impressive Objective To determine whether a structured programme of parent anticipatory guidance ‘ Toddlers Without Tears , ’ delivered in universal primary care , can prevent preschool child behaviour problems . Design Cluster r and omised controlled trial . Setting / participants 40 primary care nursing centres ( clusters ) in metropolitan Melbourne , Australia . 733 English-speaking mothers of 6- to 7-month-old infants consecutively recruited from well-child appointments ; 589 ( 80 % ) retained at age 3 years . Intervention Parenting programme from age 8 to 15 months , with two group sessions co-led by well-child providers and a parenting expert . The programme addressed normal behaviour development and offered strategies to increase desired and reduce unwanted behaviour . While 93 % of intervention parents received at least some of the programme , only 49 % completed all components . Control Usual primary care . Main outcome measures Maternal report of child externalising behaviour ( Child Behaviour Checklist ) , parenting ( Parent Behaviour Checklist ) and maternal mental health ( Depression Anxiety Stress Scales ) when children were aged 3 years . Results Behaviour scores in the intervention and control groups were similar ( mean ( SD ) ) 11.4 ( 7.1 ) versus 12.4 ( 7.6 ) ; adjusted mean difference −0.8 , 95 % CI −2.2 to 0.6 , p=0.26 ) . On the parenting subscale scores , intervention parents reported fewer unreasonable expectations of child development ( 37.3 ( 10.9 ) vs 39.9 ( 10.2 ) , adjusted mean difference −3.1 , 95 % CI −4.9 to −1.4 , p=0.001 ) . The mean scores for harsh/abusive and nurturing parenting , and maternal mental health , were similar between the two groups . Conclusions A brief universal parenting programme in primary care is insufficient to prevent development of preschool externalising problems . A new population trial targeting more intensive prevention to distressed parents with toddler behaviour problems is now under way , aim ing to prevent externalising and internalising problems before school entry . Trial registration number IS RCT BACKGROUND To test effectiveness of a parenting intervention , delivered in a community-based voluntary-sector organisation , for reducing conduct problems in clinical ly-referred children . METHODS R and omised controlled trial , follow-up at 6 , 18 months , assessors blind to treatment status . Participants --76 children referred for conduct problems , aged 2 - 9 , primarily low-income families , r and omised to treatment vs. 6-month wait-list group . Retention was 93 % at 6 months , 90 % at 18 months . Interventions --Webster-Stratton Incredible Years video-based 14-week group programme , teaches cognitive-behavioural principles for managing behaviour , using a collaborative , practical , problem-solving approach . Primary outcomes --child problem behaviour by parent-report ( Eyberg ) and home-based direct observation ; secondary outcomes --observed positive and negative parenting ; parent-reported parenting skill , confidence and depression . RESULTS Post-treatment improvements were found in child problem behaviour , by parent-report ( effect size ( ES ) .48 , p = .05 ) and direct observation ( ES .78 , p = .02 ) ; child independent play ( ES .77 , p = .003 ) ; observed negative ( ES .74 , p = .003 ) and positive ( ES .38 , p = .04 ) parenting ; parent-reported confidence ( ES .40 , p = .03 ) and skill ( ES .65 , p = .01 ) , using ANCOVA to control for baseline scores . Maternal depression did not change . Consumer satisfaction was high . At 18-month follow-up , although no r and omised comparison was possible , changes appeared to maintain , with no significant change toward baseline level on any measure . Change in observed positive parenting appeared to mediate change in child problem behaviour ( p < .025 ) . CONCLUSIONS Findings suggest that a group-based cognitive-behavioural parenting programme , delivered by well-trained and supervised staff , can be effective in a community voluntary-sector setting , for reducing conduct problems and enhancing parenting skills . Change in parenting skill appears to be a key mechanism for change in child behaviour . Findings have implication s for feasibility of translating evidence -based programmes , even for clinical ly-referred conduct problems , into less specialised community setting s , likely to have lower costs and be more accessible for families Objective To evaluate the effectiveness of a parenting programme as a preventive intervention with parents of preschool children considered to be at risk of developing conduct disorder . Design Pragmatic r and omised controlled trial using a block design with allocation by area . Setting Eleven Sure Start areas in north and mid-Wales . Participants 153 parents from socially disadvantaged areas , with children aged 36 - 59 months at risk of conduct disorder defined by scoring over the clinical cut off on the Eyberg child behaviour inventory . Participants were r and omised on a 2:1 basis , 104 to intervention and 49 to remaining on the wait listing ( control ) . Twenty ( 13 % ) were lost to follow-up six months later , 18 from the intervention group . Intervention The Webster-Stratton Incredible Years basic parenting programme , a 12 week group based intervention . Main outcome measures Problem behaviour in children and parenting skills assessed by self reports from parents and by direct observation in the home . Parents ' self reported parenting competence , stress , and depression . St and ardised and well vali date d instruments were used throughout . Results At follow-up , most of the measures of parenting and problem behaviour in children showed significant improvement in the intervention group . The intention to treat analysis for the primary outcome measure , the Eyberg child behaviour inventory , showed a mean difference between groups of 4.4 points ( 95 % confidence interval 2.0 to 6.9 , P<0.001 ) on the problem scale with an effect size of 0.63 , and a mean difference of 25.1 ( 14.9 to 35.2 , P<0.001 ) on the intensity scale with an effect size of 0.89 . Conclusion This community based study showed the effectiveness of an evidence based parenting intervention delivered with fidelity by regular Sure Start staff . It has influenced policy within Wales and provides lessons for Engl and where , to date , Sure Start programmes have not been effective . Trial registration IS RCT An adaptation of the Coping With Depression Course ( CWDC ) was evaluated in mothers of children with attention-deficit/hyperactivity disorder ( ADHD ) , a population at risk for depression . Mothers were r and omly assigned to receive the CWDC either immediately following an intensive summer treatment program targeting their child 's behavior or after a wait-list period . Measures of maternal functioning , cognitions about child behavior , parent-child and marital relationship quality , child behavior , and ADHD-related family impairment were obtained at pretreatment , posttreatment , and 5-month follow-up . The CWDC result ed in improvements in maternal depressive symptoms , maternal self-esteem , child-related cognitions , and family impairment at posttreatment compared to a wait-list control group that were maintained at follow-up . Findings suggest that the CWDC is a promising intervention for mothers of children with ADHD , particularly those with current depressive symptomatology Objective To determine whether a parenting programme , offered universally in primary care , can prevent behavioural problems in children and improve parenting and maternal mental health . Design Cluster r and omised trial . Setting 40 primary care nursing centres ( clusters ) in Victoria , Australia . Participants 733 English speaking mothers of 8 month old children sequentially recruited from well child appointments ; 656 retained at 24 months . Intervention Structured three session programme at age 8 - 15 months , co-led by well child providers and a parenting expert . The programme covered normal development and behaviour , strategies to increase desired behaviour , and strategies to reduce unwanted behaviour . Main outcome measures Maternal report of child externalising behaviour ( child behavior checklist 1½-5 year old ) , parenting ( parent behavior checklist ) , and maternal mental health ( depression anxiety stress scales ) at 18 and 24 months . Results At 18 months , child behaviour and parenting scores were similar in the two groups . At 24 months , externalising scores in the intervention and control groups were similar ( mean 11.9 ( SD 7.2 ) v 12.9 ( 7.4 ) ) ; however , on the parent behavior checklist subscale scores , intervention group parents were less likely to report harsh/abusive parenting ( mean 38.9 ( SD 7.7 ) v 40.5 ( 8.8 ) ; adjusted mean difference −1.83 , 95 % confidence interval −3.12 to −0.55 ) and unreasonable expectations of child development ( 40.9 ( 9.9 ) v 42.7 ( 9.6 ) ; −2.18 , −3.74 to −0.62 ) . Mean scores for nurturing parenting and maternal mental health were similar in the two groups at both times . Conclusions A universal parenting programme result ed in modest improvement in parenting factors that predict behavioural problems in children but did not reduce externalising behavioural problems or affect maternal mental health at 2 years . Trial registration IS RCT N 77531789 Background : Members of families headed by single mothers are at increased risk of psychosocial disadvantage and mental health problems . We assessed the effect of a community-based program of social support and education groups for single mothers of young children on maternal well-being and parenting . Methods : We recruited 116 single mothers of children 3 to 9 years old through community advertisements . Eligible mothers were r and omly assigned either to participate in a 10-week program of group sessions ( 1.5 hours per week ) offering social support and education , with a parallel children 's activity group , or to receive a st and ard list of community re sources and the option to participate in group sessions at the end of the follow-up period . Interviewers blinded to the r and omization collected assessment data from all mothers at baseline and at 3 follow-up visits ( immediately after the intervention and at 3 and 6 months after the intervention ) . Outcome measures were self-reported mood , self-esteem , social support and parenting . Results : Between February 2000 and April 2003 , the program was offered to 9 groups of single mothers . Most of the mothers in the trial reported high levels of financial and mental health problems . In the short term ( after the intervention ) , mothers in the intervention group had improved scores for mood ( p < 0.01 , st and ardized effect = 0.55 ) and self-esteem ( p < 0.05 , st and ardized effect = 0.29 ) compared with mothers in the control group ; scores for the other 2 measures did not differ between the groups . Growth curve analysis of program effects over the follow-up period showed improvement in all 4 outcomes , with no significant difference between the intervention and control groups . Interpretation : This community-based program of group sessions offering social support and education to low-income single mothers had positive short-term effects on mood and self-esteem but not on social support and parenting . Longer follow-up showed attenuation of these effects OBJECTIVE To determine if a nurse-led or psychologist-led parent-training program was more successful than a minimal intervention in treating early childhood Oppositional Defiant Disorder ( ODD ) in pediatric primary care . METHODS Twenty-four practice s were r and omized to conditions in which parents of 117 , 3- to 6.11-year-olds with ODD received the 12-session Webster-Stratton Incredible Years program led by primary care nurses or clinical psychologists , or to a minimal intervention group in which parents received only the companion book to the treatment program . RESULTS There was improvement across posttreatment and 12-month follow-up for all groups , but no overall treatment group effects . There was a dose effect , with a reliable , clinical ly significant gain after seven sessions on the Eyberg intensity scale , and nine sessions on the Child Behavior Checklist externalizing scale . CONCLUSIONS There is little advantage to the therapist-led treatment over bibliotherapy unless parents attend a significant number of sessions The Infant Health and Development Program is a two-generation early education model design ed to improve parenting competence and child well-being . As part of an 8-site r and omized clinical trial involving low birthweight premature children , assessment s of children and parents were gathered at the time of program completion ( age 3 ) , with follow-up at ages 5 , 8 , and 18 . Two key parenting processes were assessed at age 18 based on theory stipulating the central ity of parenting to long-term development in children . Analyses based on 283 control group and 178 Infant Health and Development Program treatment group participants revealed that treatment group mothers scored higher on one , the provision of enriching experiences . Evidence of sustained impacts on parenting suggests that carefully structured two-generation early education programs may prove good investments for promoting competence and adaptive functioning in high-risk children The effectiveness of a parent training program for promoting positive parent-child relationships was examined among families of 2-year-olds . Forty-six mothers and fathers and their toddlers were assigned to either an intervention or comparison group . Intervention group parents participated in a 10-week program that focused on principles for effectively interacting with their toddlers . Parents completed measures of parenting self-efficacy , depression , stress , and perceptions of their toddler 's behaviors and were videotaped playing with their toddlers preintervention , postintervention , and 3 months following the intervention . Repeated measures ANOVAs showed that the parent training program led to significant increases in maternal self-efficacy , decreases in maternal stress , and improvements in the quality of mother-toddler interactions . No significant effects were found among fathers . Explanations for obtaining different outcomes for mothers and fathers are discussed and directions for future research are recommended The aim of the present study was to evaluate whether a short parent-training program ( PT ) reduces risk factors related to development of childhood socio-emotional and behavior problems in a non- clinical community sample . Data were obtained from parents in a r and omized controlled trial ( RCT ) on PT for children aged 2 to 8 years ( N=186 ) at pre-intervention , post-intervention and one-year-follow up . There were significant differences in the changes in the two groups , with reductions in harsh parenting and child behavior problems , an enhancement of positive parenting and of the parents ' sense of competence in the intervention group . The effects on parenting and parents ' satisfaction all lasted through one-year follow up . Our findings suggests that a shortened version of a well-structured parenting intervention , The Incredible Years program , implemented in primary care at community level , reduces harsh parenting and strengthens positive parenting and parents ' sense of competence , as reported by the parents . Issues related to a public health approach to promote positive parenting are discussed A significant percentage of children with disruptive behavior disorders do not receive mental health assistance . Utilization is lowest among groups whose children are at greatest risk . To increase the availability , accessibility , and cost efficacy of parent training programs , this prospect i ve r and omized trial compared a large group community-based parent training program to a clinic-based individual parent training ( PT ) programs . All families of junior kindergartners in the Hamilton public and separate school boards were sent a checklist regarding problems at home . Those returning question naires above the 90th percentile were block r and omly assigned to : ( 1 ) a 12-week clinic-based individual parent training ( Clinic/Individual ) , ( 2 ) a 12-week community-based large group parent training ( Community/Group ) , or ( 3 ) a waiting list control condition . Immigrant families , those using English as a second language , and parents of children with severe behaviour problems were significantly more likely to enroll in Community/Groups than Clinic/Individual PT . Parents in Community/Groups reported greater improvements in behaviour problems at home and better maintenance of these gains at 6-month follow-up . A cost analysis showed that , with groups of 18 families , Community/Groups are more than six times as cost effective as Clinic/Individual programs OBJECTIVE The Training and Support Program ( TSP ) was design ed to equip parents of children with disabilities with a simple massage skill for use with their children in the home environment . The effectiveness of the TSP was examined in a r and omized controlled trial with a wait-list control group . METHODS Parents were trained in massage by suitably qualified therapists in eight weekly sessions , each lasting 1 h. The sample comprised 188 parents who were r and omized to an intervention group ( n=95 ) , who attended the TSP with their children immediately , or a control group ( n=93 ) , who were offered the TSP after 4 months of follow-up . Data were collected by self-administered question naires at baseline and at 4-month follow-up . RESULTS The majority of participants were mothers ( 88 % ) , with a partner ( 88 % ) , and White European ( 82 % ) ; 40 % worked full-time or part-time , and 34 % had health problems ( e.g. , chronic fatigue , cancer , and arthritis ) . The TSP demonstrated statistically significant positive effects on parental self-efficacy ( PSE ) for managing children 's psychosocial well-being and depressed mood ( 0.004 and 0.007 ) . There were trends toward improvement on parental satisfaction with life ( P=.053 ) , global health ( P=.065 ) , and parental ratings of children 's sleeping ( P=.074 ) and mobility ( P=.012 ) . Effect sizes were small ( 0.11 - 0.23 ) . Levels of anxiety , depression , and perceived stress were all higher than published norms . CONCLUSION The TSP is an effective means of improving PSE and depressed mood . Additional means of supporting parents need to be investigated The effectiveness of a behavioral parent training ( BPT ) intervention for improving maternal self-efficacy , maternal stress , and the quality of mother-toddler interactions has been demonstrated ( Gross , Fogg , & Tucker , 1995 ) . The 1-year follow-up of the 46 parents of toddlers ( assigned to an intervention or comparison group ) who participated in that study is reported . It was hypothesized that ( a ) BPT would lead to enduring positive changes in parenting self-efficacy , parenting stress , and parent-toddler interactions ; and ( b ) the amount of parent participation in the intervention would be correlated with greater gains in parent-child outcomes at 1 year . All the families were retained and significant gains in maternal self-efficacy , maternal stress , and mother-child interactions were maintained . Minimal BPT effects were found for fathers . BPT dosage was related to reductions in mother critical statements and negative physical behaviors at 1-year postintervention . The findings are consistent with self-efficacy theory and support parenting self-efficacy as a target for BPT in families of young children The present study is the first European evaluation of the Canadian parent training programme called Community Parent Education Program ( COPE ) . In addition , it is the first to examine the effects of the COPE programme in different types of clinical and non clinical sample s. The main findings were that COPE was found to be effective in reducing conduct problems , hyperactivity/impulsivity , daily problem behaviours , parental stress , and lack of perceived parental control . However , the programme was not effective in reducing inattention , social competence deficits , or peer problems . Interestingly , the significant group effects were a result of significant differences between the two non clinical intervention groups and the waiting-list control group , whereas the clinical intervention group did not differ significantly from the control group with regard to either child or parental variables . This points to the importance of evaluating parent training programmes in groups with different levels of severity so that parents are offered the type of training programme most suitable for their child 's needs This study assessed the role of social support in the outcome of child management training ( CMT ) for single parents of conduct problem children and assessed the impact of adjunctive ally support training ( AST ) on treatment outcome . Single parents ( N = 22 ) with a child diagnosed as oppositional or conduct-disordered received CMT or CMT plus AST . Each group received the same 6-week parent training program and the AST group received an extra social support intervention . Measures of parent behavior , child deviance , social support ( SS ) , and parental depression were obtained at pre- and posttreatment and at 6-month follow-up . Both groups improved , and changes maintained at follow-up . AST produced no extra gains . Responders from either group were more likely than nonresponders to report high levels of SS from friends . Results emphasize the importance of SS and the difficulty of incorporating changes in SS into treatment programs BACKGROUND Preterm infants are at increased risk of cognitive , motor and behavioral problems . Different intervention programs have been design ed in an attempt to improve outcome , but the results are conflicting . OBJECTIVE To examine the effects of an early intervention program on cognitive , motor and behavioral problems and parenting stress among low birth weight children at 2 years corrected age . METHODS A r and omized controlled trial was conducted including infants with a birth weight < 2000 g treated at the University Hospital of North Norway , to examine the effects of a modified version of the Mother-Infant Transaction Program on cognitive , motor and behavioral outcomes and parenting stress . The children were assessed with the Bayley Scales of Infant Development and the Child Behavior Checklist/2 - 3 ( CBCL ) and the Parenting Stress Index were administered to the parents at 2 years corrected age . RESULTS Sixty-nine children in the intervention group and 67 in the control group were assessed at 2 years . There were no differences between the groups in cognitive or motor outcomes . The intervention group scored consistently lower on all CBCL syndrome scales , but no difference was significant . The mothers in the intervention group reported significantly lower parental stress in both child and parent domain , whereas the fathers reported lower stress in child domain compared to the control group . CONCLUSION This early intervention program does not improve cognitive , motor or behavioral outcomes at 2 years . There was a significant reduction in parenting stress reported by both mothers and fathers in the intervention group OBJECTIVE This r and omized control trial examined the effects of a short-term , interaction-focused and attachment-based video-feedback intervention ( VIPP : video-feedback intervention to promote positive parenting ) . Design VIPP effect on mothers ' sensitive responsiveness and infant-mother attachment security was evaluated in a sample ( n = 54 ) of low sensitive , non- clinical , middle class Lithuanian mothers . METHODS Maternal sensitivity was assessed in a free play session with the Ainsworth 's sensitivity scale , and attachment security was observed using the Attachment Q sort for home observations . RESULTS We found that the intervention mothers indeed significantly improved their sensitive responsiveness through participation in our VIPP . The effect size was large according to Cohen 's criteria , d = 0.78 . VIPP enhanced maternal sensitive responsiveness even when maternal age , educational level , depression , daily hassles , efficacy , infant gender , and infant negative and positive affect were controlled for . However , attachment security in the VIPP infants was not enhanced after the intervention , compared with the control infants , and the infants did not seem to be differentially susceptible to the increase in maternal sensitivity dependent on their temperamental reactivity . CONCLUSION We suggest that a relatively brief and low-cost programme can provide effective support for mothers who lack sensitivity in the interactions with their infants The aim of this r and omized controlled trial was to evaluate the efficacy of an evidence -based parenting program ( the Triple P-Positive Parenting Program ) , intending to improve parenting skills and children 's well-being . Parents participating in a Group Triple P program ( n=50 couples ) were compared with parents of a non-treated control group ( n=50 couples ) and parents participating in a marital distress prevention program ( couples coping enhancement training ( CCET ) ) ( n=50 couples ) . The two major goals of this study were ( a ) to evaluate the efficacy of Triple P compared with the two other treatment conditions over a time-span of 1 year and ( b ) to answer the question whether this program that was developed in Australia is culturally accepted by Swiss parents . Results revealed that Triple P was effective with Swiss families . Mothers of the Triple P group showed significant improvements in parenting , parenting self-esteem , and a decrease in stressors related to parenting . Women trained in Triple P also reported significantly lower rates of child 's misbehavior than women of the two other conditions . However , in men only a few significant results were found . Positive effects of the relationship training ( CCET ) were somewhat lower than those for the Triple P. These findings are further discussed We examined parent and child moderators of outcome , program engagement effects , and predictors of engagement in the Incredible Years Parent Training Program . Head Start classrooms ( N = 882 children ) were r and omly assigned to an intervention condition ( that received the Incredible Years program ) or to a control condition ( that received usual Head Start services ) . Structural equation modeling ( SEM ) was used to model the effects of the training program on child outcomes . The analyses showed differential program effects depending on children 's initial levels of conduct problems and mothers ' initial levels of critical parenting . Children with high baseline levels of conduct problems and children of mothers with high initial levels of critical parenting benefited most from the program . Changes in children 's conduct problems were also related to maternal engagement in the program and to intervention mothers ' success at reducing their critical parenting 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 This study evaluated parental engagement in an 8-week parenting program offered through daycare centers that were r and omly assigned to a monetary incentive or nonincentive condition . Of an initial sample of 1,050 parents who rated their intent to enroll in the program , 610 went on to enroll—319 in the incentive and 291 in the nonincentive condition . Results showed that intent to enroll predicted enrollment irrespective of condition . Further , parents did not enroll in greater numbers , attend more sessions , or participate more actively in the incentive condition . Incentives encouraged some parents , often younger and socioeconomically disadvantaged , to enroll but had no effect on their attendance . Of importance , these results could not be accounted for by between-condition differences in child and family or in daycare characteristics Despite the potential of parent training as a prevention and behavioral family intervention strategy , there are a number of important issues related to implementation ( e.g. , recruitment and retention of families ) . This paper presents recruitment and retention data from families enrolling in a r and omized controlled universal prevention trial for child behavior problems conducted in Germany . The recruitment rate averaged 31 % ( general project participation ) , with families of lower socioeconomic status ( SES ) participating at a lower rate . Project-declining families most often reported intrusion of privacy as their primary concern . In contrast , once parents were enrolled in the project , participation among those r and omized to the parent training group averaged 77 % ( program/intervention participation ) ; non-participation was mostly due to logistical issues . Parents accepting the offer of parent training were more likely to report child behavior problems than did declining parents . Although parents from more disadvantaged areas had a lower overall level of participation in the project once recruited , parents with children having higher levels of behavior problems indeed were more likely to participate in the intervention . Different recruitment methods may be required to engage high-risk families from socioeconomically disadvantaged areas to further improve community-level impact on child mental health Objective : Although behavioral parenting programs are effective at treating child behavioral problems , a significant number of parents experiencing these problems do not receive help , and briefer , more cost-effective parenting interventions are lacking . This study aim ed to evaluate the efficacy of a brief parenting discussion group . Method : Sixty-seven parents were r and omly assigned to either an intervention or waitlist control condition . Parents in the intervention condition took part in a 2-hour discussion group in which they were taught positive parenting strategies to prevent and manage their child 's disobedience , and they received 2 follow-up telephone calls after the discussion group . Results : Results showed that after intervention , there were reductions in child behavior problems and use of dysfunctional parenting and improvements in parental self-efficacy and the parenting experience for parents . These effects were maintained at 6-month follow-up . Conclusion : The results are promising because they show that a brief intervention can be minimally sufficient to improve child and parent outcomes for parents experiencing high levels of child behavior problems This study examined whether a group educational intervention during the transition to parenthood can enhance the quality of father-child interaction and increase father involvement with their children . A r and omized experimental design was used to evaluate an 8-session program with 165 couples who were first-time parents , beginning during the second trimester of pregnancy and ending at 5 months postpartum . Outcomes were assessed with time diaries , coded observations of parent-child play , and self-reports of fathers and mothers . The intervention had positive effects on fathers ' skills in interacting with their babies and their involvement on work days but not home days . It is concluded that a relatively brief intervention during the transition to parenthood can improve fathering , and possible reasons for differential effects on areas of parenting are explored We evaluated the efficacy of a manualized multimodal treatment program for young externalizing children . Families were assigned r and omly to an immediate 12-week parent and child treatment condition ( n = 24 ) or to a delayed-treatment condition ( n = 23 ) . Parents had high attendance , high satisfaction with treatment , and increased knowledge of behavior management principles . Relative to the waitlist condition , treatment parents reported statistically and clinical ly significant reductions in child behavior problems , improved parenting practice s ( i.e. , increased consistency , decreased power assertive techniques ) , an increased sense of efficacy , and reduced parenting stress . There was a trend toward parents improving their attitudes toward their children . In considering the process of change , we found evidence that improved parenting practice s mediated reductions in child behavior problems and that child improvements mediated changes in parent attitudes and stress . Five months following treatment , teachers reported significant improvements in child behaviors , whereas parents reported that reductions in child behavior problems and parenting stress were maintained This study compared the effectiveness of a culturally modified version of Parent – Child Interaction Therapy ( PCIT ) , called Gui and o a Niños Activos ( GANA ) , to the effectiveness of st and ard PCIT and Treatment as Usual ( TAU ) for young Mexican Amerian children with behavior problems . Fifty-eight Mexican Amerian families whose 3- to 7-year-old child had a clinical ly significant behavior problems were r and omly assigned to GANA , st and ard PCIT , or TAU . All three treatment approaches produced significant pre – post improvement in conduct problems across a wide variety of parent-report measures . GANA produced results that were significantly superior to TAU across a wide variety of both parent report and observational indices ; however , GANA and PCIT did not differ significantly from one another . PCIT was superior to TAU on two of the parent report indices and almost all of the observational indices . There were no significant differences between the three groups on treatment dropout , and families were more satisfied with both GANA and PCIT than with TAU BACKGROUND Parent training ( PT ) is identified as the most effective intervention for the treatment of conduct disorder ( CD ) . Intervention observational outcomes are often reported as summarised composite scores , providing an overview of overall construct change . METHODS AND AIMS Parents of children aged 3 - 5 years identified ' at risk ' of developing CD were r and omly allocated to either PT intervention or waiting list control group . Parent and child behaviours were assessed before and after the intervention period . The current paper aims to establish which individual observed parenting categories change as a result of PT , and which specific observed leader categories predict these changes . RESULTS Controlling for baseline scores , ANCOVA demonstrated changes in parent praise and reflective behaviours as significant post-intervention . One-way ANOVAs demonstrated higher levels of leader praise and reflective behaviours result ed in greater change in parental praise and reflective behaviours respectively . Regression analyses indicated these leader behaviours predict positive change in parental praise and reflective behaviours for intervention families . CONCLUSIONS Composite observational scores provide an account of behaviour constructs , whereas individual behaviour categories provide an insight into the core components of these constructs . The results suggest praise and reflection as key leader behaviours that influence the mechanisms of change in parenting behaviours as a result of PT The revised new forest parenting programme ( NFPP ) is an 8-week psychological intervention design ed to treat ADHD in preschool children by targeting , amongst other things , both underlying impairments in self-regulation and the quality of mother – child interactions . Forty-one children were r and omized to either the revised NFPP or treatment as usual conditions . Outcomes were ADHD and ODD symptoms measured using question naires and direct observation , mothers ’ mental health and the quality of mother – child interactions . Effects of the revised NFPP on ADHD symptoms were large ( effect size > 1 ) and significant and effects persisted for 9 weeks post-intervention . Effects on ODD symptoms were less marked . There were no improvements in maternal mental health or parenting behavior during mother – child interaction although there was a drop in mothers ’ negative and an increase in their positive comments during a 5-min speech sample . The small-scale trial , although limited in power and generalizability , provides support for the efficacy of the revised NFPP . The findings need to be replicated in a larger more diverse sample The efficacy of the Incredible Years parent training and child therapy programs was examined in a r and omized controlled study including 127 Norwegian children aged 4–8 years . Children diagnosed with oppositional defiant disorder ( ODD ) or conduct disorder ( CD ) were r and omized to parent training ( PT ) , parent training combined with child therapy ( PT + CT ) , or a waiting-list control condition ( WLC ) . Assessment s were carried out at baseline , posttreatment and at a one-year follow-up using st and ardized measures and a semi-structured interview . Both active treatment conditions reduced child conduct problems posttreatment as opposed to the WLC , while differences between the two treatment conditions were small and nonsignificant . About two thirds of the treated children functioned within normal variation after treatment , and the same proportion no longer received an ODD diagnosis at the one-year follow-up . Parental use of positive strategies increased after treatment , and the use of harsh and inconsistent discipline decreased as did mother experience of stress . The outcome of this study emphasizes the importance of offering parent training to young children with severe conduct problems exhibited at home . The findings and usefulness of the Incredible Years program in the present Norwegian replication study further support and extend positive outcomes of previous controlled trials conducted primarily in Anglo-Saxon countries This study evaluates the initial efficacy of the Parent-Child Interaction Therapy ( PCIT ) for Puerto Rican preschool children aged 4 - 6 years with a diagnosis of attention-deficit/hyperactivity disorder ( ADHD ) , combined or predominantly hyperactive type , and significant behavior problems . Thirty-two families were r and omly assigned to PCIT ( n = 20 ) or a 3.5-month waiting-list condition ( WL ; n = 12 ) . Participants from both groups completed pretreatment and posttreatment assessment s. Outcome measures included child 's ADHD symptoms and behavior problems , parent or family functioning , and parents ' satisfaction with treatment . ANCOVAs with pretreatment measures entered as covariates were significant for all posttreatment outcomes , except mother 's depression , and in the expected direction ( p < .01 ) . Mothers reported a highly significant reduction in pretreatment hyperactivity and inattention and less aggressive and oppositional-defiant behaviors , conduct problems assessed as problematic , parenting stress associated with their child 's behavior , and an increase in the use of adequate parenting practice s. For the WL group , there were no clinical ly significant changes in any measure . Treatment gains obtained after treatment were maintained at a 3.5-month follow-up assessment . PCIT seems to be an efficacious intervention for Puerto Rican families who have young children with significant behavior problems Studied the effectiveness of parent and teacher training as a selective prevention program for 272 Head Start mothers and their 4-year-old children and 61 Head Start teachers . Fourteen Head Start centers ( 34 classrooms ) were r and omly assigned to ( a ) an experimental condition in which parents , teachers , and family service workers participated in the prevention program ( Incredible Years ) or ( b ) a control condition consisting of the regular Head Start program . Assessment s included teacher and parent reports of child behavior and independent observations at home and at school . Construct scores combining observational and report data were calculated for negative and positive parenting style , parent-teacher bonding , child conduct problems at home and at school , and teacher classroom management style . Following the 12-session weekly program , experimental mothers had significantly lower negative parenting and significantly higher positive parenting scores than control mothers . Parent-teacher bonding was significantly higher for experimental than for control mothers . Experimental children showed significantly fewer conduct problems at school than control children . Children of mothers who attended 6 or more intervention sessions showed significantly fewer conduct problems at home than control children . Children who were the " highest risk " at baseline ( high rates of noncompliant and aggressive behavior ) showed more clinical ly significant reductions in these behaviors than high-risk control children . After training , experimental teachers showed significantly better classroom management skills than control teachers . One year later the experimental effects were maintained for parents who attended more than 6 groups . The clinical ly significant reductions in behavior problems for the highest risk experimental children were also maintained . Implication s of this prevention program as a strategy for reducing risk factors leading to delinquency by promoting social competence , school readiness , and reducing conduct problems are discussed This study examined the effects of Pathways Triple P ( PTP ) , an early intervention program design ed to promote positive parent-child relationships . Sixty parents met the inclusion criteria of borderline to clinical ly significant relationship disturbance and child emotional and behavioral problems . They were r and omly allocated into PTP or a wait-list ( WL ) control group . PTP was delivered in a group format for 9 weeks and consisted of parent skills training and cognitive behavior therapy targeting negative attributions for child behavior . Significant intervention effects were found for improving parent-child relationships and reducing behavior problems with gains maintained at 3-month follow-up . Limitations of the study and implication s for future research are discussed OBJECTIVE To assess the impact of maternal attention-deficit/hyperactivity disorder ( ADHD ) symptoms on the effectiveness of a parent training ( PT ) program for preschool ADHD . METHOD Eighty-three 3-year-old children with ADHD and their mothers selected from two community cohorts living in Hampshire , Engl and ( 1992 - 93 and 1995 - 96 , respectively ) , completed an 8-week PT program . ADHD symptoms and a number of other parent and child factors , including adult ADHD symptoms , were measured prior to the start of treatment ( week 1 : T1 ) , immediately after treatment ( week 8 : T2 ) , and at 15 weeks follow-up ( week 23 : T3 ) . RESULTS Mothers were divided into three groups on the basis of their scores ( T1 ) on the Adult AD/HD Rating Scale ( high , medium , low ) . Children of mothers in the high-ADHD group displayed no improvement after PT , whereas the levels of ADHD symptoms of the children of mothers in either the medium or low ADHD groups reduced substantially ( F(4,60 ) = 3.13 , p < .05 ) . This association persisted after other child and maternal factors were controlled for in multiple regression analyses ( beta > .30 , p < .05 ) . CONCLUSIONS High levels of maternal ADHD symptoms limit the improvement shown by children with ADHD after a program of PT . This effect was unrelated to other aspects of maternal mental health and child functioning . The treatment of parental ADHD may be a prerequisite for the success of psychosocial interventions for childhood ADHD In previous work , Luthar and Suchman ( 2000 , Development & Psychopathology , 12 , 235 ) reported results of a r and omized clinical trial testing the efficacy of the Relational Psychotherapy Mothers ' Group ( RPMG ) for methadone-maintained mothers . In this extension , we examined maternal interpersonal maladjustment as a predictor of differential response to RPMG versus st and ard drug counseling ( DC ) . We predicted that RPMG mothers with high levels of interpersonal maladjustment would improve on parent-child relationship indices , whereas DC mothers with high levels of interpersonal maladjustment would show no improvement . Fifty-two mothers enrolled in the study completed baseline , post-treatment and 6-month followup assessment s and a subset of 24 " target " children between the ages of 7 and 16 completed measures on mothers ' parenting . As predicted , results of hierarchical regression analyses indicated moderate interpersonal maladjustment x treatment interaction effects for all parenting outcomes at post-treatment and for a subset of outcomes at followup . Plotted interactions confirmed predictions that , as maternal interpersonal maladjustment increased , parenting problems improved for RPMG mothers and remained the same or worsened for DC mothers . Results indicate the potential value of interpersonally oriented interventions for substance-abusing mothers and their children The effect of a short-term group intervention to reduce self-blame and guilt in parents of children with severe disabilities was examined . Thirty-four mothers were r and omly assigned to treatment and waiting list control groups . They participated in classes led by a counselor on topics relating to cognitive processes associated with guilt and self-blame . Results showed significant reductions in measures of guilt , negative automatic thoughts , internal negative attributions , and depression . Theoretical and treatment literature concerning self-blame and guilt was briefly review ed and the derivative treatment was described This report discusses the development of a coping skill training program for parents of substance-abusing adolescents and presents preliminary data on the effects of the program on parent functioning and adolescent substance use . The behavioral-analytic model of program development was used to sample representative problematic situations experienced by parents of substance-abusing adolescents , obtain an effectiveness-scaling of responses to these situations , and derive alternate forms of a situational role-play measure of parental coping . These situations and scoring guidelines were then used to create the skill training program . Parents of substance-abusing adolescents not in treatment subsequently were r and omly assigned in a pilot investigation to either a skill training or delayed treatment condition . Skill training result ed in significant improvement in parental coping skills relative to delayed treatment . Moderate to large improvement in the parent 's report of their own functioning , family communication , and the teen 's marijuana use also favored the skill training group OBJECTIVE To assess the effectiveness of a behavioural programme introduced in the first 3 months of age in preventing infant crying and sleeping problems . Two issues were addressed : ( i ) which elements of the behavioural programme would parents implement ; and ( ii ) whether the behavioural programme was more effective in reducing infant crying and encouraging night-time sleeping than an educational intervention or the routine services . METHODOLOGY Mothers and newborns were assigned at r and om to the behavioural programme ( n = 205 ) , educational intervention ( n = 202 ) , or control ( n = 203 ) group . Behaviour diaries kept before r and omization and at 3 , 6 , 9 and 12 weeks of age were used to measure implementation of the interventions and infant behaviour , including crying and sleeping . Crying and sleeping problems were followed up using question naire measures at 9 months of age . RESULTS The educational intervention did not change parental care behaviour . One element of the behavioural programme , a focal feed between 10 PM and midnight , was not implemented . A second element , stretching of interfeed intervals after 3 weeks of age , was implemented initially , but not maintained at older ages . The third element , which asked parents to emphasise day and night differences in the environment , and to settle their babies in the cot and minimise interaction at night , was carried out by more parents in the behavioural group than in the other groups . This led to an increase of around 10 % in the number of babies who slept for 5 or more hours at night ( a definition of sleeping through the night ) at 12 weeks of age . Fewer behavioural programme parents sought help for crying and sleeping problems between 3 and 9 months of age . CONCLUSION The behavioural programme produced a modest increase in the number of infants who slept through the night by 12 weeks of age . The results are discussed in relation to other findings , which bear on the programme 's adoption for routine health-care policy and practice OBJECTIVE To investigate the effectiveness of behavioral parent training ( BPT ) as adjunct to routine clinical care ( RCC ) . METHOD After a first phase of RCC , 94 children with attention-deficit/hyperactivity disorder ( ADHD ) ages 4 - 12 , all referred to a Dutch outpatient mental health clinic , were r and omly assigned to 5 months of BPT plus concurrent RCC ( n = 47 ) or to 5 months of RCC ( n = 47 ) alone . BPT consisted of 12 sessions in group format ; RCC included family support and pharmacotherapy when appropriate . Exclusionary criteria were minimized , and children with and without medication could participate . Parent-reported behavioral problems , ADHD symptoms , internalizing problems , and parenting stress were assessed before and after treatment . Follow-up assessment of the BPT + RCC group was completed 25 weeks post-BPT intervention . Repeated- measures analyses of variance were carried out on an intention-to-treat basis . RESULTS Both groups showed improvements over time on all measures . BPT + RCC was superior to RCC alone in reducing behavioral ( p = .017 ) and internalizing ( p = .042 ) problems . No outcome differences were found in ADHD symptoms ( p = .161 ) and parenting stress ( p = .643 ) . These results were equal for children with and without medication . Children allocated to RCC alone received more polypharmaceutical treatment . CONCLUSIONS Adjunctive BPT enhances the effectiveness of routine treatment of children with ADHD , particularly in decreasing behavioral and internalizing problems , but not in reducing ADHD symptoms or parenting stress . Furthermore , adjunctive BPT may limit the prescription of polypharmaceutical treatment AIM Parenting programmes have been shown to improve children 's adjustment and reduce problem behaviour ; however , little research has addressed outcomes for Indigenous families . The aim of this project was to assess the impact and cultural appropriateness of a parenting programme tailored for Indigenous families , an adaptation of the evidence -based Group Triple P - Positive Parenting Program . METHODS A repeated measures r and omised group design methodology was used , comparing the intervention with a waitlist control condition pre- and post-intervention , with a 6-month follow-up of the intervention group . RESULTS Parents attending Group Triple P reported a significant decrease in rates of problem child behaviour and less reliance on some dysfunctional parenting practice s following the intervention in comparison to waitlist families . The programme also led to greater movement from the clinical range to the non-clinic range for mean child behaviour scores on all measures . Effects were primarily maintained at 6-month follow-up . Qualitative data showed generally positive responses to the programme re sources , content and process . However , only a small number of waitlist families subsequently attended groups , signalling the importance of engaging families when they first make contact , helping families deal with competing dem and s , and offering flexible service delivery so families can resume contact when circumstances permit . CONCLUSIONS This study provides empirical support for the effectiveness and acceptability of a culturally tailored approach to Group Triple P conducted by Child Health and Indigenous Health workers in a community setting . The outcomes of this trial may be seen as a significant step in increasing appropriate service provision for Indigenous families and reducing barriers to accessing available services in the community BACKGROUND Traditional Korean American discipline is characterized by a lack of expression of affection and use of harsh discipline . OBJECTIVE The purpose of this study was to pilot test the effect of the Incredible Years Parenting Program among Korean American mothers . METHODS A r and omized controlled experimental study design was used ; 29 first-generation Korean American mothers of young children ( 3 - 8 years old ) were r and omly assigned to intervention ( n=20 ) and control ( n=9 ) groups . Intervention group mothers received a 12-week parenting program . Control group mothers did not receive the intervention . Mothers reported on discipline styles ( positive , appropriate , and harsh ) , level of acculturation , and their child 's outcomes ( behavioral problems and social competence ) at pre- , post- , and 1-year follow-up intervals . RESULTS After completing the program , intervention group mothers significantly increased use of positive discipline as compared to control group mothers . Among intervention group mothers , high-acculturated mothers significantly increased appropriate discipline whereas low-acculturated mothers significantly decreased harsh discipline . In the 1-year follow-up , intervention group mothers maintained the significant effect for positive discipline . CONCLUSIONS Providing this program appears to be a promising way of promoting positive discipline among Korean American mothers This study evaluates the Better Parenting Programme ( BPP ) which has been implemented nationally in Jordan to enhance parents ’ knowledge , attitudes , and behaviours related to caring for young children . The participants ( N = 337 , 94 % female ) were r and omly assigned to an experimental group or a control group . The experimental group participated in the BPP ; the control group did not . Before and after the BPP , all participants completed question naires to assess their knowledge regarding key areas of child development , activities with their children , discipline practice s , and perceptions regarding behaviours that constitute child abuse and neglect . Over time , the participants in the experimental group ( but not those in the control group ) improved on parenting knowledge , spending time playing and reading books with their children , using more explanations during the course of disciplining their child , and accurately perceiving behaviours that constitute child neglect . The results suggest modest beneficial effects of participation in the BPP BACKGROUND Behavioural parent training is effective in improving child disruptive behavioural problems in preschool children by increasing parenting competence . The indicated Prevention Programme for Externalizing Problem behaviour ( PEP ) is a group training programme for parents and kindergarten teachers of children aged 3 - 6 years with externalizing behavioural problems . AIMS To evaluate the effects of PEP on child problem behaviour , parenting practice s , parent-child interactions , and parental quality of life . METHOD Parents and kindergarten teachers of 155 children were r and omly assigned to an intervention group ( n = 91 ) and a nontreated control group ( n = 64 ) . They rated children 's problem behaviour before and after PEP training ; parents also reported on their parenting practice s and quality of life . St and ardized play situations were video-taped and rated for parent-child interactions , e.g. parental warmth . RESULTS In the intention to treat analysis , mothers of the intervention group described less disruptive child behaviour and better parenting strategies , and showed more parental warmth during a st and ardized parent-child interaction . Dosage analyses confirmed these results for parents who attended at least five training sessions . Children were also rated to show less behaviour problems by their kindergarten teachers . CONCLUSIONS Training effects were especially positive for parents who attended at least half of the training sessions . ABBREVIATIONS CBCL : Child Behaviour Checklist ; CII : Coder Impressions Inventory ; DASS : Depression anxiety Stress Scale ; HSQ : Home-situation Question naire ; LSS : Life Satisfaction Scale ; OBDT : observed behaviour during the test ; PCL : Problem Checklist ; PEP : prevention programme for externalizing problem behaviour ; PPC : Parent Problem Checklist ; PPS : Parent Practice s Scale ; PS : Parenting Scale ; PSBC : Problem Setting and Behaviour checklist ; QJPS : Question naire on Judging Parental Strains ; SEFS : Self-Efficacy Scale ; SSC : Social Support Scale ; TRF : Caregiver-Teacher Report Form The effectiveness of the Incredible Years Parenting Program was evaluated in a low-income sample of Caucasian , African American , Hispanic , and Asian mothers whose children were enrolled in Head Start . Data from two prior intervention studies [ Webster-Stratton ( 1998 ) Journal of Consulting and Clinical Psychology , 66(5 ) , 715–730 ; Webster-Stratton et al. ( in press ) Journal of Clinical Child Psychology ] were combined , yielding a sample of 634 families ( 370 Caucasian , 120 African American , 73 Asian , 71 Hispanic ) across 23 Head Start centers . Centers were matched and assigned r and omly to either an experimental condition ( 8–12 weeks of weekly 2-hr parenting classes ) , or a control condition ( the regular Head Start Program without parenting groups ) . Families in both conditions were assessed using home observations of parent – child interactions and parent reports of parenting style and discipline strategies and child behavior problems in the fall ( baseline ) and spring ( postintervention ) of the children 's Head Start year . Families were reassessed 1 year later . Following treatment , intervention mothers were observed to be more positive , less critical , more consistent , and more competent in their parenting than were control mothers . Additionally , children of intervention parents were observed to exhibit fewer behavior problems than were control children . Differences in treatment response across ethnic groups were few , and did not exceed the number expected by chance . Parents from all groups reported high satisfaction levels following the parenting program . Results indicate that the Incredible Years Program is accepted by and effective with diverse population Twenty-four parents of oppositional preschoolers were r and omly assigned to either a selfdirected behavioral family intervention condition ( SD ) or to a waitlist control group ( WL ) . The self-directed parent training program , based on self-regulation principles , consisted of a written information package and weekly telephone consultations for 10 weeks . At posttest , in comparison to the WL group , children in the SD group had lower levels of behavior problems on parent report measures of child behavior . At posttreatment , parents in the SD condition reported increased levels of parenting competence and lower levels of dysfunctional parenting practice s as compared to parents in the WL condition . In addition , mothers reported lower levels of anxiety , depression , and stress as compared to mothers in the WL condition at posttreatment . Using mother 's reports , gains in child behavior and parenting practice s achieved at posttreatment were maintained at 4-month follow-up This study tested the efficacy of a 12-session parent training program , the Chicago Parent Program ( CPP ) , which was developed in collaboration with African American and Latino parents . Using growth curve modeling , data were analyzed from 253 parents ( 58.9 % African American , 32.8 % Latino ) of 2–4 year old children enrolled in seven day care centers serving low-income families . Day care centers were matched and r and omly assigned to intervention and waiting-list control conditions . At 1-year follow-up , intervention group parents used less corporal punishment and issued fewer comm and s with their children . Intervention children exhibited fewer behavior problems during observed play and clean-up sessions than controls . Additional group differences were observed when dose was included in the analytic model . Parents who participated in at least 50 % of CPP sessions also reported greater improvements in parenting self-efficacy , more consistent discipline , greater warmth , and a decline in child behavior problems when compared to reports from controls . The implication s of these results for preventive parent training with low-income African American and Latino parents and the role of intervention dose on parent – child outcomes are discussed The efficacy of a self-help parent training programme for children with attention deficit hyperactivity disorder ( ADHD ) was evaluated . The New Forest Parenting Programme Self-help ( NFPP-SH ) is a 6-week written self-help psychological intervention design ed to treat childhood ADHD . Forty-three children were r and omised to either NFPP-SH intervention or a waiting list control group . Outcomes were child ADHD symptoms measured using question naires and direct observation , self-reported parental mental health , parenting competence , and the quality of parent – child interaction . Measures of child symptoms and parental outcomes were assessed before and after the intervention . ADHD symptoms were reduced , and parental competence was increased by self-help intervention . Forty-five percent of intervention children showed clinical ly significant reductions in ADHD symptoms . Self-help intervention did not lead to improvements in parental mental health or parent – child interaction . Findings provide support for the efficacy of self-help intervention for a clinical sample of children with ADHD symptoms . Self-help may provide a potentially cost-effective method of increasing access to evidence -based interventions for clinical population An experimental research study was done to determine whether an educational intervention about attention deficit hyperactivity disorder ( ADHD ) would improve a mother 's knowledge about ADHD and her feelings of competence as a parent . 20 low socioeconomic status mothers who had a male child between the ages of 5 and 11 diagnosed with ADHD and placed on methylpheni date were r and omly selected for the study . An experimental group of 10 mothers was given a 5-week educational intervention on ADHD ; the remaining 10 mothers served as a control group . Differences between the experimental and non-experimental mothers in knowledge and opinions about ADHD and parental sense of competency were measured . Scores improved in parental satisfaction and parental sense of competency in mothers who participated in the educational intervention . The research findings support the idea that nurses can assist a family in learning and dealing with their child 's ADHD , a chronic condition Three variants of a behavioral family intervention ( BFI ) program known as Triple P were compared using 305 preschoolers at high risk of developing conduct problems . Families were r and omly assigned to enhanced BFI ( EBFI ) , st and ard BFI ( SBFI ) , self-directed BFI ( SDBFI ) , or wait list ( WL ) . At postintervention , the 2 practitioner-assisted conditions were associated with lower levels of parent-reported disruptive child behavior , lower levels of dysfunctional parenting , greater parental competence , and higher consumer satisfaction than the SDBFI and WL conditions . Overall , children in EBFI showed greater reliable improvement than children in SBFI , SDBFI , and WL . By 1-year follow-up , children in all 3 conditions achieved similar levels of clinical ly reliable change in observed disruptive behavior . However , the EBFI and SBFI conditions showed greater reliable improvement on parent-observed disruptive child behavior A r and omized controlled trial was used to evaluate a parent training intervention for caregivers with preschool-age children with developmental disabilities . The 21 families in the experimental group received usual care plus the 12-week Incredible Years Parent Training Program with developmental delay modifications . Families in the control group ( n = 23 ) received usual care , including early childhood education and related services . Results suggest that this parent training intervention was superior to usual care for young children with developmental delays or disabilities in reducing negative parent-child interactions and child behavior problems . Participants in the experimental group indicated high satisfaction with treatment . Additional research is necessary to document maintenance and generalization of treatment outcomes The present study assessed use of a psychoeducation group program on expressed emotion , family functioning , and child behavior by parents of children with learning disorders . 81 parents of children with learning disorders were r and omly assigned to a psychoeducation group program ( n = 46 ) or to a regular treatment group ( n = 35 ) . A semistructured interview for parental expressed emotion , self-reports of family functioning , and child behavior were utilized at baseline and after an 8-session psychoeducation group program . Parents who attended the program differed significantly from parents in the regular treatment group on measures of criticism , warmth , and positive remarks , and overall expressed emotion , but not on measures of perceived family functioning and child behavior . Findings indicate a psychoeducation group program could be effective in helping parents to establish a more positive emotional climate in their relationships with their children who have learning disorders Parents of gifted children identify a need for tailored parenting support , and gifted children have unique requirements and vulnerabilities . The aim of this study was to assess the efficacy of a tailored behavioural parenting intervention , for enhancing the parenting skills of parents of gifted children and to assess the effect of these changes on the behavioural and emotional adjustment of their gifted child . A r and omised controlled trial of tailored Group Triple P - Positive Parenting Program was conducted with 75 parents of children identified as gifted . Results indicated significant intervention effects for the number and frequency of parent reported child behaviour problems , as well as hyperactivity in the intervention group , relative to a waitlist control . Parents also reported significant improvements in their own parenting style , including less permissiveness , harshness , and verbosity when disciplining their child . No intervention effects were evident for teacher reports , except for a trend in relation to hyperactivity . This study demonstrated that a tailored behavioural parenting intervention is effective and acceptable for parents of gifted children , and thus has clinical implication s for the delivery of parenting interventions for this population The effects of parent education programs on the parenting attitudes and abilities of 30 U.S. male inmates and on the self-perceptions of their children ( aged 8 - 17 years ) were examined . Inmates were pre- and post-tested with the Adult-Adolescent Parenting Inventory and the Index of Self-Esteem . The children were administered the Self-Perception Profile for Children or the Self-Perception Profile for Adolescents . Participants in the experimental group completed a 6-week program including parental training and behavior-management training . The control group 's 6-week program consisted of viewing family-related videotapes , answering questions , and discussing the contents of the videotapes . Parent education improved the attitudes of inmates toward appropriate parenting but did not significantly change their children 's self-perceptions OBJECTIVE Describes outcomes of an intervention aim ed to improve infant or toddler care and reduce parental distress . METHODS A r and omized controlled trial method was used with 118 mothers . Participants were allocated to an intervention group ( n = 65 ) or an enhanced waitlist group ( n = 53 ) . Measures were taken at pre- , post- , and 6-weeks follow-up . RESULTS Results demonstrated that mothers who attended the program reported improvement in depression , anxiety , stress , parental satisfaction , and decreases in problematic child behavior . Improvements were maintained at the 6-week follow up . Intention-to-treat analysis replicated the results , although with smaller effect sizes . CONCLUSIONS The results of this study demonstrate that delivery of a 1 day intervention for distressed mothers can contribute to lower levels of parental distress and child problem behavior . Given the importance of early mother-child relationships and the limited number of well-controlled studies on brief interventions this result is of significance to research ers and the service community To examine the impact of paying for participation in a preventive parenting program on treatment outcomes , 197 families with preschool-aged children were r and omized to paid or unpaid conditions . Although both groups improved on nearly all measures , paid families showed less improvement on 3 of 10 variables , including father-reported child prosocial behavior and parenting skills and maternal distress . The interaction between payment and treatment format ( individual vs. group ) was examined . Compared to unpaid group participants , paid group intervention participants had significantly worse mother and father parenting skills posttreatment , whereas paid individual intervention mothers had significantly better skills . These findings suggest payment may lead to smaller treatment effects , although the bulk of the data point to no impact on outcomes . Given that payment attracts families who would not otherwise receive treatment , this appears to be a viable strategy to recruit families without appreciably impacting outcomes Whilst the Triple P Positive Parenting Program has a large evidence base ( S and ers , Clinical Child and Family Psychology Review 2:71–90 , 1999 ; S and ers , Journal of Consulting and Clinical Psychology 68:624–640 , 2000 ) and preliminary evidence indicates that Stepping Stones Triple P is also efficacious ( Roberts , Journal of Clinical Child and Adolescent Psychology , 35(2):180–193 , 2006 ) , to date Stepping Stones has not been evaluated with the ASD population . Fifty-nine families with a child with ASD aged between 2 and 9 participated in this r and omized controlled trial . The results demonstrate significant improvements in parental reports of child behaviour and parenting styles with the treatment effects for child behaviour , parental over reactivity and parental verbosity being maintained at follow-up 6 months later . Further , the results suggest significant improvements in parental satisfaction and conflict about parenting as well as a sleeper effect for parental efficacy . The results indicate that Stepping Stones Triple P is a promising intervention for parents of children with ASD . Limitations and future research are also addressed OBJECTIVES To determine the effectiveness of a psychosocial intervention , provided to expectant couples in routine antenatal classes , on the postpartum psychosocial adjustment of women and men . DESIGN A 3 * 3 between subjects r and omised control design was utilised . The two factors were condition and self-esteem . Preparation for Parenthood programs were r and omly allocated to one of three conditions : usual service ( ' control ' ) , experimental ( ' empathy ' ) , or non-specific control ( ' baby-play ' ) . The latter condition controlled for the non-specific effects of the intervention , these being : the provision of an extra class ; asking couples to consider the early postpartum weeks ; and receiving booster information after the antenatal class , and again shortly after the birth . Women and men were categorised into three levels of self-esteem , as measured antenatally : low , medium and high . METHODS 268 participants were recruited antenatally . Interview data and self-report information was collected from 202 of these women at 6 weeks postpartum , and 180 women at 6 months postpartum . The intervention consisted of a session focusing on psychosocial issues related to becoming first-time parents . Participants discussed possible postpartum concerns in separate gender groups for part of the session , and then discussed these issues with their partners . Hypothetical scenarios depicting stressful situations in the early postpartum weeks for women and men were discussed , with solutions that parents have found useful given to the participants . In the non-specific control condition , the session focused on the importance of play with a baby , with videotapes and discussion around how parents can play with infants . RESULTS At 6 weeks postpartum there was a significant interaction effect between condition and self-esteem on maternal adjustment . Women with low self-esteem , who had received the intervention , were significantly better adjusted on measures of mood and sense of competence than low-self-esteem women in either of the two control conditions . There were no main or interaction effects by 6 months postpartum . The beneficial effect at 6 weeks was related to partners of these women being more aware of how the mother was feeling , and with women reporting greater satisfaction with the sharing of home and baby tasks . There were no significant main or interaction effects for men at either time point , other than men with low self-esteem reporting poorer adjustment . CONCLUSIONS This brief and inexpensive intervention was effective in reducing postpartum distress in some first-time mothers at 6 weeks postpartum . The effectiveness of this intervention was related to an increased level of awareness in the men as to how their partners were experiencing the early postpartum weeks . That the effect was only evident for women who , antenatally , reported being low in self-esteem , is an important advance in our knowledge of the effectiveness of such prevention programs . No previous studies have investigated the differential effectiveness of such programs depending upon the woman 's level of self-esteem , and this finding indicates that future work should measure this variable . These findings should be understood in the context that the population sample d were those attending preparation for parenthood classes , and thus different interventions will be needed for couples who do not attend such classes . This brief psychosocial intervention can be readily applied to antenatal classes routinely conducted in hospitals or the community Objective : We performed a r and omized , controlled trial to assess the impact of the Video Interaction Project ( VIP ) , a program based in pediatric primary care in which videotaped interactions are used by child development specialists to promote early child development . Method : Ninety-nine Latino children ( 52 VIP , 47 controls ) at risk of developmental delay based on poverty and low maternal education were assessed at age 33 months . VIP was associated with improved parenting practice s including increased teaching behaviors . Results : VIP was associated with lower levels of parenting stress . VIP children were more likely to have normal cognitive development and less likely to have developmental delays . Conclusion : This study provides evidence that a pediatric primary care – based intervention program can have an impact on the developmental trajectories of at-risk young preschool children OBJECTIVE To determine the impact of a parent education and behavior management intervention ( PEBM ) on the mental health and adjustment of parents with preschool children with autism . METHOD A r and omized , group-comparison design involving a parent education and counseling intervention to control for nonspecific therapist effects and a control sample was used . Two metropolitan and two rural regions were r and omly allocated to intervention groups ( n = 70 ) or control ( n = 35 ) . The parents of consecutive children with autism ( 2(1/2)-5 years old ) from the autism assessment services for the intervention regions were then r and omly allocated to either a 20-week manual-based parent education and behavior management intervention ( n = 35 ) or a manual-based parent education and counseling intervention ( n = 35 ) . The main outcome measure of parental mental health was the General Health Question naire used pre- and postintervention and at 6-month follow-up . RESULTS Both treatments result ed in significant and progressive improvement in overall mental health at follow-up ( F = 2 , 97 , p = .007 ) and mental health significantly improved over time in the 54 % of principal caregivers who had the highest levels of mental health problems . The parent education and behavior management intervention was effective in alleviating a greater percentage of anxiety , insomnia , and somatic symptoms and family dysfunction than parent education and counseling at 6-month follow-up . CONCLUSIONS A 20-week parent education and skills training program for parents of young children newly diagnosed with autism provides significant improvements in parental mental health and adjustment , justifying its addition to early intervention programs at least for parents with mental health problems This article presents the results of a pilot study of the Marriage Moments program , design ed to prevent relationship deterioration during the 1st year of parenthood . The self-guided , low-intensity program emphasizes strengthening marital virtues and partnership during this time of significant personal and family transition . One hundred fifty-five married couples participated in a r and omized clinical trial with 2 psychoeducational treatment groups ( a self-guided group and an instructor-encouraged group ) and a comparable control group . Despite positive formative evaluation results from program participants , hierarchical linear modeling analyses failed to find significant Group x Time differences on spouses ' reports of marital virtues and a set of relational outcome measures . This failure reinforces the need for psychoeducators to invest in outcome evaluation research before cl aim ing program success This study provided a r and omized , experimental test of the efficacy of a parent training intervention on coercive discipline , positive parenting practice s , and child noncompliance in a sample of 238 divorcing mothers and their sons in Grade s 1 - 3 . Intervention effects were evaluated 5 times from baseline to 30 months . The intervention produced enduring benefits to coercive discipline , positive parenting , and boys ' noncompliance . These benefits followed a classic prevention effect : Mothers and sons in the experimental group maintained stable outcome trajectories , whereas those in the control group deteriorated . The intervention 's impact on boys ' noncompliance was mediated independently by its impact on coercive discipline and positive parenting . Change in positive parenting was more strongly associated with change in noncompliance than was change in coercive discipline , although each explained unique variance in change in noncompliance This study examined effectiveness of a Group Curriculum ( GC ) for parents of 3- to 6- year-old children with disruptive behavior . The curriculum is based on the book Parenting the Strong-Willed Child . A total of 39 parents were r and omly assigned to the GC condition or a wait-list control condition . Assessment s occurred at baseline , postintervention ( 6 weeks after baseline ) , and 2-month follow-up . Findings indicated that the GC condition was associated with lower levels of child problem behavior and improved parenting at postintervention relative to the control condition . Parents were also satisfied with the intervention . Uncontrolled 2-month follow-up data suggested that changes were maintained from postintervention to follow-up for all outcome measures This study evaluated a parent problem-solving ( PPS ) intervention design ed to augment the effects of evidence -based therapy for children referred to treatment for aggressive and antisocial behavior . All children ( N = 127 , ages 6 - 14 years ) and their families received problem-solving skills training ( PSST ) , and parents received parent management training ( PMT ) . Families were r and omly assigned to receive or not to receive an additional component ( PPS ) that addressed parental stress over the course of treatment . Children improved with treatment ; the PPS intervention enhanced therapeutic change for children and parents and reduced the barriers that parents experienced during treatment . The implication s of the findings for improving evidence -based treatment as well as the limitations of adding components to treatment are detailed Parental competencies have great impact on child development . The concept of parental competency is a comprehensive construct , that involves functional and dysfunctional rearing behavior as well as evaluation of parental coping with challenging rearing situations and self-efficacy of rearing . Enhancing parental education is an important challenge on the background of high prevalence rates of child behavior problems . In the present r and omised controlled study the effects of a Triple P parent training on parental competence was examined . 280 families were r and omly assigned to a training of a control group . After pre- assessment , the training group participated in a Triple P parent training . 6 and 12 month after pre- assessment , post- and follow-up-1-year- assessment s were conducted . Mothers in the training group showed significantly increased parental competencies compared to the control group . Especially overt functional and dysfunctional rearing behavior changed positively . Fathers showed no such change , but did often also not participate in the training . The study illustrates that parental competence can be promoted through Triple This article reports results from an early intervention program aim ed at preventing the development of anxiety in preschool children . Children were selected if they exhibited a high number of withdrawn/inhibited behaviors -- one of the best identified risk factors for later anxiety disorders-- and were r and omly allocated to either a 6-session parent-education program or no intervention . The education program was group based and especially brief to allow the potential for public health application . Children whose parents were allocated to the education condition showed a significantly greater decrease in anxiety diagnoses at 12 months relative to those whose parents received no intervention . However , there were no significant effects demonstrated on measures of inhibition/withdrawal . The results demonstrate the value of ( even brief ) very early intervention for anxiety disorders , although these effects do not appear to be mediated through alterations of temperament Summary ¶ Background : Poor compliance by participants consenting to be r and omised to receive both physical and mental health promotion interventions represents a potentially serious threat to external and internal validity of those interventions . Quantitative and qualitative investigation of possible predictors of engagement forms an appropriate basis for efforts to enhance it . Methods : Eight ‘ Preparing for Parenthood ’ intervention courses of a r and omized controlled trial ( RCT ) underpinned a quantitative study . One ‘ Preparing for Parenthood ’ ( PFP ) intervention course , run upon completion of the RCT , formed a qualitative study . All nine courses followed identical procedures to enable clear comparisons . The three factors quantitatively explored with respect to engagement in health promoting behaviours were : locus of control ( LOC ) , psychosocial support , and life events . The qualitative study utilised grounded theory analysis , the participants reflecting upon their experiences of the intervention and /or their reasons for not attending the course ; nine interviews were completed . Results : Participants in the quantitative and qualitative studies were divided into three sub-groups : compliant , non-compliant , and refusers . None of the three health promoting variables predicted compliance to a statistically significant degree . However , a variable from the trial analysis was found to reach significance ; those women who had had less contact with the National Health Service in the 12 months prior to the baseline assessment were more likely to refuse the invitation to PFP . The qualitative study produced nine main themes that had influenced participant engagement at both the initial recruitment stage and during the course itself . Conclusions : In combination these findings may contribute to the future design of both effective and acceptable interventions to prevent postnatal depression . One such modified intervention is described and its impact on engagement outlined Examined efficacy of an empirically based intervention using 70 divorced mothers who participated in a 12-session program or a wait-list condition . The program targeted five putative mediators : quality of the mother-child relationship , discipline , negative divorce events , contact with fathers , and support from nonparental adults . Posttest comparisons showed higher quality mother-child relationships and discipline , fewer negative divorce events , and better mental health outcomes for program participants than controls . More positive program effects occurred for mothers ' than children 's reports of variables and for families with poorest initial levels of functioning . Analyses indicated that improvement in the mother-child relationship partially mediated the effects of the program on mental health This r and omized experimental prevention study ( a ) evaluated the effectiveness of a parent-training program in a sample of 238 divorcing mothers with sons in Grade s 1 - 3 and ( b ) provided an experimental test of coercion theory . The intervention produced reductions in observed coercive parenting , prevented decay in positive parenting , and generally improved effective parenting practice s in comparisons of mothers in experimental and control groups . Moreover , coercion theory was supported . Improved parenting practice s correlated significantly with improvements in teacher-reported school adjustment , child-reported maladjustment , and mother-reported maladjustment . The intervention indirectly benefitted child outcomes through improved parenting practice s for a model based on child report and , to a lesser extent , on teacher report . The intervention did not produce direct effects on child outcomes Abstract . Few attempts have been made to conduct r and omised control trials ( RCTs ) of interventions for pre-school children with autism . We report findings of a pilot RCT for a parent training intervention with a focus on the development of joint attention skills and joint action routines . Twenty-four children meeting ICD-10 criteria for childhood autism ( mean age = 23 months ) were identified using the CHAT screen and r and omised to the parent training group or to local services only . A follow-up was conducted 12 months later ( mean age = 35 months ) . There was some evidence that the parent training group made more progress in language development than the local services group . However , the present pilot study was compromised by several factors : a reliance on parental report to measure language , non-matching of the groups on initial IQ , and a lack of systematic checking regarding the implementation of the parent training intervention . Furthermore , three parents in the local services group commenced intensive , home-based behavioural intervention during the course of the study . The difficulties encountered in the conduct of RCTs for pre-school children with autism are discussed . Method ological challenges and strategies for future well- design ed RCTs for autism interventions are highlighted This study investigated the ability of a theoretically driven , psychosocial prevention program implemented through childbirth education programs to enhance the coparental relationship , parental mental health , the parent-child relationship , and infant emotional and physiological regulation . A sample of 169 heterosexual , adult couples who were expecting their 1st child was r and omized to intervention and control conditions . The intervention families participated in Family Foundations , a series of 8 classes , delivered before and after birth , that was design ed as a universal prevention program ( i.e. , it was applicable to all couples , not just those at high risk ) . Intent-to-treat analyses indicated significant program effects on coparental support , maternal depression and anxiety , distress in the parent-child relationship , and several indicators of infant regulation . Intervention effects were not moderated by income , but greater positive impact of the program was found for lower educated parents and for families with a father who reported higher levels of insecure attachment in close relationships . These findings support the view that coparenting is a potentially malleable intervention target that may influence family relationships as well as parent and child well-being |
10,345 | 29,283,475 | An integrated evaluation should be also applied to patients with a high arrhythmic risk , in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk .
Evaluation of LA size , volume , function and structure are m and atory in the management of patients with HT , HFpEF and AF .
A multi-modality approach could provide additional information , identifying subjects with more severe LA remodelling . | AIM Functional analysis and measurement of left atrium are an integral part of cardiac evaluation , and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension ( HT ) and /or heart failure with preserved ejection fraction ( HFpEF ) .
However , diastolic dysfunction remains quite elusive regarding classification , and atrial size and function are two key factors for left ventricular ( LV ) filling evaluation .
Chronic left atrial ( LA ) remodelling is the final step of chronic intra-cavitary pressure overload , and it accompanies increased neurohormonal , proarrhythmic and prothrombotic activities .
In this systematic review , we aim to purpose a multi-modality approach for LA geometry and function analysis , which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools . | Background — Atrial fibrillation ( AF ) is common among patients with heart failure and preserved ejection fraction ( HFpEF ) , but its clinical profile and impact on exercise capacity remain unclear . RELAX ( Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF ) was a multicenter r and omized trial testing the impact of sildenafil on peak VO2 in stable out patients with chronic HFpEF . We sought to compare clinical features and exercise capacity among patients with HFpEF who were in sinus rhythm ( SR ) or AF . Methods and Results — RELAX enrolled 216 patients with HFpEF , of whom 79 ( 37 % ) were in AF , 124 ( 57 % ) in SR , and 13 in other rhythms . Participants underwent baseline cardiopulmonary exercise testing , echocardiogram , biomarker assessment , and rhythm status assessment before r and omization . Patients with AF were older than those in SR but had similar symptom severity , comorbidities , and renal function . & bgr;-blocker use and chronotropic indices were also similar . Despite comparable left ventricular size and mass , AF was associated with worse systolic ( lower EF , stroke volume , and cardiac index ) and diastolic ( shorter deceleration time and larger left atria ) function compared with SR . Pulmonary artery systolic pressure was higher in AF . Patients with AF had higher N-terminal pro-B-type natriuretic peptide , aldosterone , endothelin-1 , troponin I , and C-telopeptide for type I collagen levels , suggesting more severe neurohumoral activation , myocyte necrosis , and fibrosis . Peak VO2 was lower in AF , even after adjustment for age , sex , and chronotropic response , and VE/VCO2 was higher . Conclusions — AF identifies an HFpEF cohort with more advanced disease and significantly reduced exercise capacity . These data suggest that evaluation of the impact of different rate or rhythm control strategies on exercise tolerance in patients with HFpEF and AF is warranted . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00763867 Background — Isolated atrial fibrillation ( AF ) is associated with mild enlargement of the left atrium ( LA ) and left ventricular ( LV ) diastolic dysfunction . The impact of ablation of isolated AF on left chamber size and function is unclear , and whether diastolic dysfunction is the cause or the consequence of AF remains unknown . The objective of this prospect i ve study was to evaluate the impact of sinus rhythm restoration by catheter ablation on LV diastolic dysfunction , LA morphology , and mechanical function . Methods and Results — Forty-eight patients with isolated AF were studied by serial echocardiographic studies at baseline and at 1- , 3- , 6- , 9- , and 12-month intervals after radiofrequency ablation . LA dimensions and mechanical function and LV systolic and diastolic functions were evaluated at each time interval . Diastolic function was assessed with conventional Doppler parameters and new indexes such as tissue Doppler imaging , mitral flow propagation velocity , and combined criteria . LV diastolic dysfunction was present in paroxysmal and chronic AF patients with a reduction of tissue Doppler imaging lateral early diastolic peak velocity in 37 % ( P<0.001 ) and 48 % ( P<0.01 ) , respectively , compared with healthy control subjects . At the end of the follow-up , LA area decreased significantly by 18 % ( P<0.001 ) in paroxysmal and 23 % ( P<0.05 ) in chronic AF patients . Diastolic function improved significantly with an increase in lateral early diastolic peak velocity of 29 % ( P<0.001 ) in paroxysmal AF and 46 % ( P<0.05 ) in chronic AF patients . A significant increase in LV ejection fraction was also noted for both groups : 7.7 % and 18.8 % , respectively . Conclusions — This study demonstrates reverse morphological remodeling of the LA and improvement of LV diastolic and systolic functions after restoration of sinus rhythm by ablation for isolated AF . Because patients with isolated AF have none of the traditional causes of LV diastolic dysfunction , our findings suggest that AF may be partly the cause rather than the consequence of diastolic dysfunction Background —Early detection of structural changes in left atrium ( LA ) before atrial fibrillation ( AF ) development could be helpful in identification of those at higher risk for AF . Using cardiac magnetic resonance imaging , we examined the association of LA volume and function , and incident AF in a multiethnic population free of clinical cardiovascular diseases . Methods and Results —In a case – cohort study embedded in MESA ( Multi-Ethnic Study of Atherosclerosis ) , baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants r and omly selected from the whole MESA cohort . Participants were followed up for 8 years . Incident AF cases had a larger LA volume and decreased passive , active , and total LA emptying fractions and peak global LA longitudinal strain ( peak LA strain ) at baseline . In multivariable analysis , elevated LA maximum volume index ( hazard ratio , 1.38 per SD ; 95 % confidence interval , 1.01–1.89 ) and decreased peak LA strain ( hazard ratio , 0.68 per SD ; 95 % confidence interval , 0.48–0.96 ) , and passive and total LA emptying fractions ( hazard ratio for passive LA emptying fractions , 0.55 per SD ; 95 % confidence interval , 0.40–0.75 and hazard ratio for active LA emptying fractions , 0.70 per SD ; 95 % confidence interval , 0.52–0.95 ) , but not active LA emptying fraction , were associated with incident AF . Conclusions —Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population . Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development OBJECTIVES The aim of this study was to investigate the utility of a comprehensive imaging protocol including echocardiography and cardiac magnetic resonance in the diagnosis and differentiation of hypertensive heart disease and heart failure with preserved ejection fraction ( HFpEF ) . BACKGROUND Hypertension is present in up to 90 % of patients with HFpEF and is a major etiological component . Despite current recommendations and diagnostic criteria for HFpEF , no noninvasive imaging technique has as yet shown the ability to identify any structural differences between patients with hypertensive heart disease and HFpEF . METHODS We conducted a prospect i ve cross-sectional study of 112 well-characterized patients ( 62 with HFpEF , 22 with hypertension , and 28 healthy control subjects ) . All patients underwent cardiopulmonary exercise and biomarker testing and an imaging protocol including echocardiography with speckle-tracking analysis and cardiac magnetic resonance including T1 mapping pre- and post-contrast . RESULTS Echocardiographic global longitudinal strain ( GLS ) and extracellular volume ( ECV ) measured by cardiac magnetic resonance were the only variables able to independently stratify among the 3 groups of patients . ECV was the best technique for differentiation between hypertensive heart disease and HFpEF ( ECV area under the curve : 0.88 ; GLS area under the curve : 0.78 ; p < 0.001 for both ) . Using ECV , an optimal cutoff of 31.2 % gave 100 % sensitivity and 75 % specificity . ECV was significantly higher and GLS was significantly reduced in subjects with reduced exercise capacity ( lower peak oxygen consumption and higher minute ventilation-carbon dioxide production ) ( p < 0.001 for both ECV and GLS ) . CONCLUSIONS Both GLS and ECV are able to independently discriminate between hypertensive heart disease and HFpEF and identify patients with prognostically significant functional limitation . ECV is the best diagnostic discriminatory marker of HFpEF and could be used as a surrogate endpoint for therapeutic studies BACKGROUND S Paroxysmal atrial fibrillation ( AF ) frequently , but not always , progresses to persistent/permanent AF . The aim of this study was to evaluate the echocardiographic predictors of AF progression in patients with paroxysmal AF . METHODS A multicenter , prospect i ve , observational study was conducted that included 313 patients with paroxysmal AF who underwent two-dimensional speckle-tracking echocardiography . The diameter , volume , and mechanical function of the left atrium , including global strain ( ε ) and ε rate , were measured . RESULTS Progression to persistent or permanent AF occurred in 52 patients ( 16.6 % ) during a median follow-up period of 26 months . Echocardiographic measure of left atrial ( LA ) diameter , volume , and function ( E velocity , E/A and E/e ' ratio , LA expansion index , active emptying fraction , global longitudinal ε and ε rate ) were associated with AF progression . LA ε ≤ 30.9 % was the strongest predictor of AF progression , which was associated with a more than fourfold hazard increase for AF progression ( hazard ratio , 4.224 ; P = .001 ) . LA diameter > 39 mm and maximal LA volume index > 34.2 mL/m(2 ) were associated with about a twofold hazard increase for AF progression ( hazard ratios , 1.994 and 2.649 ; P = .016 and P = .001 , respectively ) . When adjusted for a model combining maximal LA volume index , E velocity , LA expansion index , and active emptying fraction , LA ε ≤ 30.9 % maintained a more than threefold hazard increase for AF progression ( adjusted hazard ratio , 3.970 ; P = .003 ) . CONCLUSIONS Echocardiographic measures of LA diameter , volume , and mechanical function , including LA ε , were associated with AF progression . LA ε was the strongest independent predictor of AF progression and is expected to serve as a valuable predictor of AF progression Background — Atrial fibrillation ( AF ) is associated with diffuse left atrial fibrosis and a reduction in endocardial voltage . These changes are indicators of AF severity and appear to be predictors of treatment outcome . In this study , we report the utility of delayed-enhancement magnetic resonance imaging ( DE-MRI ) in detecting abnormal atrial tissue before radiofrequency ablation and in predicting procedural outcome . Methods and Results — Eighty-one patients presenting for pulmonary vein antrum isolation for treatment of AF underwent 3-dimensional DE-MRI of the left atrium before the ablation . Six healthy volunteers also were scanned . DE-MRI images were manually segmented to isolate the left atrium , and custom software was implemented to quantify the spatial extent of delayed enhancement , which was then compared with the regions of low voltage from electroanatomic maps from the pulmonary vein antrum isolation procedure . Patients were assessed for AF recurrence at least 6 months after pulmonary vein antrum isolation , with an average follow-up of 9.6±3.7 months ( range , 6 to 19 months ) . On the basis of the extent of preablation enhancement , 43 patients were classified as having minimal enhancement ( average enhancement , 8.0±4.2 % ) , 30 as having moderate enhancement ( 21.3±5.8 % ) , and 8 as having extensive enhancement ( 50.1±15.4 % ) . The rate of AF recurrence was 6 patients ( 14.0 % ) with minimal enhancement , 13 ( 43.3 % ) with moderate enhancement , and 6 ( 75 % ) with extensive enhancement ( P<0.001 ) . Conclusions — DE-MRI provides a noninvasive means of assessing left atrial myocardial tissue in patients suffering from AF and might provide insight into the progress of the disease . Preablation DE-MRI holds promise for predicting responders to AF ablation and may provide a metric of overall disease progression BACKGROUND Left atrial ( LA ) enlargement facilitates induction and /or maintenance of atrial fibrillation ( AF ) . However , little is known about risk factors for AF with normal LA size . METHODS We prospect ively followed 34713 initially healthy women for incident AF . Information on echocardiographic LA size at first AF diagnosis was abstract ed from medical charts during AF confirmation . LA enlargement was defined as LA diameter > 40 mm . Using a competing risk approach , we constructed Cox proportional-hazards models to calculate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) of risk factors for incident AF with and without LA enlargement , respectively . RESULTS Among 796 women with incident AF and available LA size , 328 ( 41 % ) had LA enlargement . In multivariable competing risk models , the relationship between age and incident AF was stronger in those with ( HR 1.12 , 95 % CI 1.10 - 1.14 ) versus without ( HR 1.08 , 95 % CI 1.06 - 1.09 ) LA enlargement ( p for difference < 0.0001 ) . Body weight was associated with AF only in the presence of LA enlargement ( HR per 10 kg 1.34 , 95 % CI 1.26 - 1.43 ; versus 1.07 , 95 % CI 0.998 - 1.14 , p for difference<0.0001 ) . Hypertension and height were significantly associated with AF both in the presence ( HR 1.99 , 95 % CI 1.49 - 2.65 ; and HR per 10 cm 1.36 , 95 % CI 1.13 - 1.63 ) and absence ( 1.55 , 1.25 - 1.92 and 1.29 , 1.10 - 1.50 ) of LA enlargement ( p for difference 0.17 and 0.66 , respectively ) . CONCLUSIONS These data suggest that LA enlargement explains much of the increased AF risk associated with obesity and age . In contrast , height and hypertension appear to also influence AF risk through other mechanisms besides LA enlargement AIMS The aim of this prospect i ve study was to evaluate left atrial ( LA ) function for the prediction of increased risk of new-onset non-valvular atrial fibrillation ( AF ) . Risk stratification for new-onset AF based on LA remodelling may have a major public health impact . Although left atrial volume ( LAV ) or LA dimension have been proposed as predictors of AF , other predictive parameters of LA function have not yet been fully examined . METHODS AND RESULTS LA emptying function ( EF ) , strain rate ( SR ) , and LAV were evaluated in the apical four-chamber view by speckle tracking echocardiography in 580 consecutive adults ( age 64 ± 17 , 303 men ) without a history of atrial arrhythmias . During a follow-up period of 28 months , 32 subjects ( age 73 ± 9 , 18 men ) developed electrocardiographically confirmed AF . Subjects with new-onset AF had lower LA active EF ( 16 ± 5 vs. 28 ± 8 % , P < 0.001 ) and lower LA SR at atrial contraction ( -0.9 ± 0.2 vs. -1.4 ± 0.5 S(-1 ) , P < 0.001 ) , but larger maximum LAV index ( 59 ± 12 vs. 46 ± 16 mL/m(2 ) , P < 0.001 ) compared with non-AF subjects at baseline . In multivariate logistic regression analysis , LA active EF was the only independent predictor of new-onset AF . Using an LA active EF cut-off of ≤20 % , the sensitivity and specificity for new-onset AF based on receiver operator characteristic curve analysis were 88 and 81 % , respectively ( area under the curve : 0.92 ) . CONCLUSION Reduced LA active EF ( booster pump function ) assessed by speckle tracking echocardiography independently predicts the risk of new-onset AF , suggesting a stronger association between LA functional remodelling and AF than between LA size and AF Background The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging ( MRI ) . We established a prospect i ve registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter – defibrillator ( ICD ) that was “ non – MRI‐conditional ” ( i.e. , not approved by the Food and Drug Administration for MRI scanning ) . Methods Patients in the registry were referred for clinical ly indicated nonthoracic MRI at a field strength of 1.5 tesla . Devices were interrogated before and after MRI with the use of a st and ardized protocol and were appropriately reprogrammed before the scanning . The primary end points were death , generator or lead failure , induced arrhythmia , loss of capture , or electrical reset during the scanning . The secondary end points were changes in device setting s. Results MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD . No deaths , lead failures , losses of capture , or ventricular arrhythmias occurred during MRI . One ICD generator could not be interrogated after MRI and required immediate replacement ; the device had not been appropriately programmed per protocol before the MRI . We observed six cases of self‐terminating atrial fibrillation or flutter and six cases of partial electrical reset . Changes in lead impedance , pacing threshold , battery voltage , and P‐wave and R‐wave amplitude exceeded prespecified thresholds in a small number of cases . Repeat MRI was not associated with an increase in adverse events . Conclusions In this study , device or lead failure did not occur in any patient with a non – MRI‐conditional pacemaker or ICD who underwent clinical ly indicated nonthoracic MRI at 1.5 tesla , was appropriately screened , and had the device reprogrammed in accordance with the prespecified protocol . ( Funded by St. Jude Medical and others ; MagnaSafe Clinical Trials.gov number , NCT00907361 . OBJECTIVES The aim of this study was to evaluate left atrial volume and its changes with the phases ( active and passive ) of atrial filling , and to examine the effect of normal aging on these parameters and pulmonary vein ( PV ) flow patterns . BACKGROUND Atrial volume change with normal aging has not been adequately described . Pulmonary vein flow patterns have not been volumetrically evaluated in normal aging . Combining atrial volumes and PV flow patterns obtained using transthoracic echocardiography could estimate shifts in left atrial mechanical function with normal aging . METHODS A total of 92 healthy subjects , divided into two groups : Group Y ( young < 50 years ) and Group O ( old > or = 50 years ) , were prospect ively studied . Maximal ( Vol(max ) ) and minimal ( Vol(min ) ) left atrial volumes were measured using the biplane method of discs and by three-dimensional echocardiographic reconstruction using the cubic spline interpolation algorithm . The passive filling , conduit , and active emptying volumes were also estimated . Traditional measures of atrial function , mitral peak A-wave velocity , velocity time integral ( VTI ) , atrial emptying fraction , and atrial ejection force were measured . RESULTS As age increased , Vol(max ) , Vol(min ) , and total atrial contribution to left ventricle ( LV ) stroke volume were not significantly altered . However , the passive emptying volume was significantly higher ( 14.2 + /- 6.4 ml vs. 11.6 + /- 5.7 ml ; p = 0.03 ) whereas the active emptying volume was lower ( 8.6 + /- 3.7 ml vs. 10.2 + /- 3.8 ml ; p = 0.04 ) in Group Y versus Group O. Pulmonary vein flow demonstrated an increase in peak diastolic velocity ( Group Y vs. Group O ) with no corresponding change in diastolic VTI or systolic fraction . CONCLUSIONS Normal aging does not increase maximum ( end-systolic ) atrial size . The atrium compensates for changes in LV diastolic properties by augmenting active atrial contraction . Pulmonary vein flow patterns , although diastolic dominant using peak velocity , demonstrated no volumetric change with aging Abstract We aim ed to investigate the association between white-coat hypertension ( WCH ) and left atrial ( LA ) phasic function assessed by the volumetric and speckle tracking method . This cross-sectional study included 52 normotensive individuals , 49 subjects with WCH and 56 untreated hypertensive patients who underwent a 24-h ambulatory BP monitoring and complete two-dimensional echocardiographic examination ( 2DE ) . WCH was diagnosed if clinic blood pressure ( BP ) was elevated and 24-h BP was normal . We obtained that maximum , minimum LA and pre-A LAV volumes and volume indexes gradually and significantly increased from the normotensive subjects , throughout the white-coat hypertensive individuals to the hypertensive patients . Passive LA emptying fraction ( EF ) , representing the LA conduit function , gradually reduced from normotensive to hypertensive subjects . Active LA EF and the parameter of the LA booster pump function increased in the same direction . Similar results were obtained by 2DE strain analysis . The LA stiffness index gradually increased from normotensive controls , throughout white-coat hypertensive subjects to hypertensive patients . Clinic systolic BP was associated with LA passive EF ( β= −0.283 , p = 0.001 ) , LA active EF ( β = 0.342 , p < 0.001 ) , LA total longitudinal strain ( β= −0.356 , p < 0.001 ) , LA positive longitudinal strain ( β= −0.264 , p = 0.009 ) and LA stiffness index ( β = 0.398 , p < 0.001 ) without regard to age , BMI , left ventricular structure and diastolic function in the whole study population . In the conclusion , WCH significantly impacts LA phasic function and stiffness . Clinic systolic BP was associated with functional and mechanical LA remodeling in the whole study population Objective We aim to study left atrial ( LA ) strains in patients with hypertensive response to exercise ( HRE ) and determine their usefulness in predicting masked hypertension ( HT ) . Methods Ninety-eight normotensive patients who had HRE were included and were divided into two groups after masked HT had been diagnosed by ambulatory blood pressure monitoring . Conventional echocardiographic parameters and two-dimensional speckle-tracking echocardiography-based LA strain parameters were compared . Results Patients with masked HT have higher left ventricle mass index ( LVMI ) ( 88.1±11.3 vs. 82.5±8.7 g/m2 , P<0.05 ) , left atrium maximum volume index ( LAVI ) ( 34.5±5.1 vs. 30.2±5.6 ml/m2 , P<0.001 ) , lower global longitudinal LA strain during ventricular systole ( GLAs-res ) ( 32.5±8.9 vs. 40.2±9.1 % , P<0.001 ) , and lower global longitudinal LA strain during late diastole ( GLAs-pump ) ( 15.8±4.1 vs. 18.1±5.8 % , P<0.05 ) . In univariate analysis , a good negative correlation was found between GLAs-res versus LAVI ( r=−0.451 , P<0.001 ) , GLAs-res versus LVMI ( r=−0.457 , P<0.001 ) and a moderate negative correlation was present between GLAs-pump versus LAVI ( r=−0.317 , P<0.001 ) and GLAs-pump versus LVMI ( r=−0.288 , P<0.05 ) . GLAs-res and LAVI were found to be independent predictors of masked HT . Receiver-operating characteristic analysis was carried out . Area under the curve to predict masked HT was 0.729 ( 95 % confidence interval : 0.623–0.832 , P<0.001 ) . GLAs-res less than 33.1 % predicted masked HT with 73 % sensitivity and 61.5 % specificity . Conclusion LA strain parameters were impaired in patients with masked HT and can be used to predict the presence of masked HT in patients with HRE OBJECTIVES We sought to compare left atrial ( LA ) volume to LA area and diameter for the prediction of adverse cardiovascular outcomes . BACKGROUND The incremental value of LA volume compared with LA area or diameter as a cardiovascular risk marker has not been evaluated prospect ively for patients with sinus rhythm or atrial fibrillation ( AF ) . METHODS Left atrial size was assessed with biplane LA volume , four-chamber LA area , and M-mode dimension for 423 patients ( mean age 71 + /- 8 years , 56 % men ) who were prospect ively followed for development of first AF , congestive heart failure , stroke , transient ischemic attack , myocardial infa rct ion , coronary revascularization , and cardiovascular death . RESULTS Of the 317 subjects in sinus rhythm at baseline , 62 had 90 new events during a mean follow-up of 3.5 + /- 2.3 years . All three LA size parameters were independently predictive of combined outcomes ( all p < 0.0001 ) . The overall performance for the prediction of cardiovascular events was greatest for LA volume ( area under the receiver operator characteristic curve : indexed LA volume 0.71 ; LA area 0.64 ; LA diameter 0.59 ) . A grade d association between the degree of LA enlargement and risk of cardiovascular events was only evident for indexed LA volume . For subjects with AF , there was no association between LA size and cardiovascular events . CONCLUSIONS Left atrial volume is a more robust marker of cardiovascular events than LA area or diameter in subjects with sinus rhythm . The predictive utility of LA size for cardiovascular events in AF was poor , irrespective of the method of LA size quantitation Background and hypothesis : Systemic hypertension is the leading cause of left ventricular ( LV ) hypertrophy . The present study aim ed to investigate the mechanism of left atrial ( LA ) enlargement in patients with hypertensive heart disease during cardiac catheterization BACKGROUND The aim of this study was to investigate whether left atrial ( LA ) strain has incremental value over the CHA2DS2-VASc score for stratifying the risk for embolism in patients with atrial fibrillation ( AF ) and whether LA strain predicts poststroke mortality . METHODS Consecutive patients with paroxysmal or persistent AF with acute embolism ( 82 patients ) or without ( 204 controls ) were prospect ively enrolled . Global peak LA longitudinal strain during ventricular systole ( LAS ) was assessed during AF rhythm . Global LAS was compared between the groups in the first cross-sectional study . Then , the 82 patients with acute embolism were prospect ively followed during the second prospect i ve cohort study . RESULTS Global LAS was lower in patients with acute embolism than in controls ( P < .001 ) . Global LAS < 15.4 % differentiated patients with acute embolism from controls , with an area under the curve of 0.83 ( P < .0001 ) . In multivariate analysis , global LAS was independently associated with acute embolism ( odds ratio , 0.74 ; 95 % confidence interval , 0.67 - 0.82 ; P < .001 ) and had an incremental value over the CHA2DS2-VASc score ( P < .0001 ) . Furthermore , 26 patients with acute embolisms died during a median follow-up period of 425 days . Global LAS independently predicted mortality after embolism . CONCLUSIONS In this observational study , LA strain provided incremental diagnostic information over that provided by the CHA2DS2-VASc score , suggesting that LA strain analysis could improve the current risk stratification of embolism in patients with AF . LA strain can also predict poststroke mortality OBJECTIVE To assess the dynamic changes in left atrial volume by transthoracic three dimensional echocardiography and compare the results with those obtained by magnetic resonance imaging ( MRI ) . DESIGN AND PATIENTS 30 healthy children ( 15 boys and 15 girls , aged 8 to 13 years ) underwent examination by three dimensional echocardiography and MRI . METHODS Three dimensional echocardiography of the left atrium was performed using rotational acquisition of planes at 18 ° intervals from the parasternal window with ECG gating and without respiratory gating . Volume estimation by MRI was performed with a slice thickness of 4–8 mm and ECG triggering during breath holding in deep inspiration . A left atrial time – volume curve was reconstructed in each child . RESULTS Left atrial maximum and minimum volumes averaged 24.0 ml/m2 and 7.6 ml/m2 by three dimensional echocardiography , and 22.1 ml/m2 and 11.9 ml/m2 by MRI . The greater left atrial minimum volume in the latter was at least in part a result of breath holding . Dynamic changes in left atrial volume during the heart cycle were detectable by both methods . The higher temporal resolution of three dimensional echocardiography allowed a more precise evaluation of different phases . CONCLUSIONS Three dimensional echocardiography and MRI were both useful methods for study ing the physiological volume changes in the left atrium in children . These methods may be used for further study of the systolic and diastolic function of the heart The aim of this prospect i ve study was to evaluate the incremental value of left atrial ( LA ) function for the prediction of risk for first atrial fibrillation ( AF ) or atrial flutter . Maximum and minimum LA volumes were quantitated by echocardiography in 574 adults ( mean age 74 + /- 6 years , 52 % men ) without a history or evidence of atrial arrhythmia . During a mean follow-up period of 1.9 + /- 1.2 years , 30 subjects ( 5.2 % ) developed electrocardiographically confirmed AF or atrial flutter . Subjects with new AF or atrial flutter had lower LA reservoir function , as measured by total LA emptying fraction ( 38 % vs 49 % , p < 0.0001 ) and higher maximum LA volumes ( 47 vs 40 ml/m(2 ) , p = 0.005 ) . An increase in age-adjusted risk for AF or atrial flutter was evident when the cohort was stratified according to medians of LA emptying fraction ( < or = 49 % : hazard ratio 6.5 , p = 0.001 ) and LA volume ( > or = 38 ml/m(2 ) : hazard ratio 2.0 , p = 0.07 ) , with the risk being highest for subjects with concomitant LA emptying fractions < or = 49 % and LA volume > or = 38 ml/m(2 ) ( hazard ratio 9.3 , p = 0.003 ) . LA emptying fraction ( p = 0.002 ) was associated with risk for first AF or atrial flutter after adjusting for baseline clinical risk factors for AF or atrial flutter , left ventricular ejection fraction , diastolic function grade , and LA volume . In conclusion , reduced LA reservoir function markedly increases the propensity for first AF or atrial flutter , independent of LA volume , left ventricular function , and clinical risk factors AIMS Left atrial ( LA ) enlargement is present in the majority of heart failure with preserved ejection fraction ( HFpEF ) patients and is a marker of risk . However , the importance of LA function in HFpEF is less well understood . METHODS AND RESULTS The PARAMOUNT trial enrolled HFpEF patients ( LVEF ≥45 % , NT-proBNP > 400 pg/mL ) . We assessed LA reservoir , conduit , and pump function using two-dimensional volume indices and speckle tracking echocardiography in 135 HFpEF patients in sinus rhythm at the time of echocardiography and 40 healthy controls of similar age and gender . Systolic LA strain was related to clinical characteristics and measures of cardiac structure and function . Compared with controls , HFpEF patients had worse LA reservoir , conduit , and pump function . The differences in systolic LA strain ( controls 39.2 ± 6.6 % vs. HFpEF 24.6 ± 7.3 % ) between groups remained significant after adjustments and even in the subsets of HFpEF patients with normal LA size or without a history of AF . Among HFpEF patients , lower systolic LA strain was associated with higher prevalence of prior HF hospitalization and history of AF , as well as worse LV systolic function , and higher LV mass and LA volume . However , NT-proBNP and E/E ' were similar across the quartiles of LA function . CONCLUSIONS In this HFpEF cohort , we observed impairment in all phases of LA function , and systolic LA strain was decreased independent of LA size or history of AF . LA dysfunction may be a marker of severity and play a pathophysiological role in HFpEF . TRIAL REGISTRATION NCT00887588 AIMS The objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure ( HF ) patients stratified by left ventricular ejection fraction ( LVEF ) and to identify predictors for mortality at 1 year in each group . METHODS AND RESULTS The European Society of Cardiology Heart Failure Long-Term Registry is a prospect i ve , observational study collecting epidemiological information and 1-year follow-up data in 9134 HF patients . Patients were classified according to baseline LVEF into HF with reduced EF [ EF < 40 % ( HFrEF ) ] , mid-range EF [ EF 40 - 50 % ( HFmrEF ) ] and preserved EF [ EF > 50 % ( HFpEF ) ] . In comparison with HFpEF subjects , patients with HFrEF were younger ( 64 years vs. 69 years ) , more commonly male ( 78 % vs. 52 % ) , more likely to have an ischaemic aetiology ( 49 % vs. 24 % ) and left bundle branch block ( 24 % vs. 9 % ) , but less likely to have hypertension ( 56 % vs. 67 % ) or atrial fibrillation ( 18 % vs. 32 % ) . The HFmrEF group resembled the HFrEF group in some features , including age , gender and ischaemic aetiology , but had less left ventricular and atrial dilation . Mortality at 1 year differed significantly between HFrEF and HFpEF ( 8.8 % vs. 6.3 % ) ; HFmrEF patients experienced intermediate rates ( 7.6 % ) . Age , New York Heart Association ( NYHA ) class III/IV status and chronic kidney disease predicted mortality in all LVEF groups . Low systolic blood pressure and high heart rate were predictors for mortality in HFrEF and HFmrEF . A lower body mass index was independently associated with mortality in HFrEF and HFpEF patients . Atrial fibrillation predicted mortality in HFpEF patients . CONCLUSIONS Heart failure patients stratified according to different categories of LVEF represent diverse phenotypes of demography , clinical presentation , aetiology and outcomes at 1 year . Differences in predictors for mortality might improve risk stratification and management goals BACKGROUND The presence of heart failure ( HF ) with preserved ejection fraction ( HFPEF ) is increasingly recognized . However , prognostic factors for HFPEF remain unclear . METHODS AND RESULTS The data were derived from Shinken Data base 2004 - 2010 , a prospect i ve cohort study ( n=15,227 ) . We examined 301 consecutive HFPEF patients ( New York Heart Association Class II or greater ) and tracked them for an average 3.5 years . Cardiopulmonary exercise testing ( CPX ) , blood exams , and ultrasound cardiogram ( UCG ) were performed at the first medical examination . Acute decompensated HF ( ADHF ) admission was observed in 19 patients ( 6.3 % ) . CPX showed that the anaerobic threshold was lower ( 7.3±4.8mL/min/kg vs. 9.7±4.3mL/min/kg , p=0.02 ) and slope of the increase in ventilation to the increase in CO(2 ) output ( VE-VCO(2 ) slope ) was higher ( 40.6±8.5 vs. 34.6±7.9 , p<0.01 ) in patients with ADHF admission than those without . Serum brain natriuretic peptide ( BNP ) tended to be higher and left atrial ( LA ) dimension was significantly greater ( 47.0±15.8 mm vs. 41.0±9.9 mm , p=0.01 ) in patients with ADHF admission than those without . Multivariate analysis showed that higher VE-VCO(2 ) slope and greater LA dimension were independent determinants of ADHF admission . CONCLUSION An aggravated CPX parameter and LA dilatation were associated with ADHF admission in patients with symptomatic HFPEF , suggesting the prognostic role of cardiopulmonary dysfunction during exercise and LA remodeling in the pathogenesis of decompensated HF development in HFPEF |
10,346 | 27,377,792 | Conclusion Intervention effectiveness was variable , but several technology-enhanced interventions have demonstrated effectiveness in reducing suicidal ideation and mental health co-morbidities . | Objective Suicide prevention is a high priority .
Scalable and sustainable interventions for suicide prevention are needed to set the stage for population -level impact .
This systematic review explores how technology-enhanced interventions target suicide risk and protective factors , using the Centers for Disease Control and Prevention ( CDC , 2015 ) Risk and Protective Factors Ecological Model . | OBJECTIVE To determine whether brief intervention and contact is effective in reducing subsequent suicide mortality among suicide attempters in low and middle-income countries . METHODS Suicide attempters ( n = 1867 ) identified by medical staff in the emergency units of eight collaborating hospitals in five culturally different sites ( Campinas , Brazil ; Chennai , India ; Colombo , Sri Lanka ; Karaj , Islamic Republic of Iran ; and Yuncheng , China ) participated , from January 2002 to October 2005 , in a r and omized controlled trial to receive either treatment as usual , or treatment as usual plus brief intervention and contact ( BIC ) , which included patient education and follow-up . Overall , 91 % completed the study . The primary study outcome measurement was death from suicide at 18-month follow-up . FINDINGS Significantly fewer deaths from suicide occurred in the BIC than in the treatment-as-usual group ( 0.2 % versus 2.2 % , respectively ; chi2 = 13.83 , P < 0.001 ) . CONCLUSION This low-cost brief intervention may be an important part of suicide prevention programmes for underre source d low- and middle-income countries ABSTRACT BACKGROUND Despite improvements in the diagnosis and treatment of depression , primary care provider ( PCP ) discussion regarding suicidal thoughts among patients with depressive symptoms remains low . OBJECTIVE To determine whether a targeted depression public service announcement ( PSA ) video or an individually tailored interactive multimedia computer program ( IMCP ) leads to increased primary care provider ( PCP ) discussion of suicidal thoughts in patients with elevated risk for clinical depression when compared to an attention control . DESIGN R and omized control trial at five different healthcare systems in Northern California ; two academic , two Veterans Affairs ( VA ) , and one group-model health maintenance organization ( HMO ) . PARTICIPANTS Eight-hundred sixty-seven participants , with mean age 51.7 ; 43.9 % women , 43.4 % from a racial/ethnic minority group . INTERVENTIONThe PSA was targeted to gender and socio-economic status , and design ed to encourage patients to seek depression care or request information regarding depression . The IMCP was an individually tailored interactive health message design ed to activate patients to discuss possible depressive symptoms . The attention control was a sleep hygiene video . MAIN MEASURES Clinician reported discussion of suicidal thoughts . Analyses were stratified by depressive symptom level ( Patient Health Question naire [ PHQ-9 ] score < 9 [ mild or lower ] versus ≥ 10 [ at least moderate]).KEY RESULTS Among patients with a PHQ-9 score ≥ 10 , PCP discussion of suicidal thoughts was significantly higher in the IMCP group than in the control group ( adjusted odds ratio = 2.33 , 95 % confidence interval = 1.5 , 5.10 , p = 0.03 ) . There were no significant effects of either intervention on PCP discussion of suicidal thoughts among patients with a PHQ-9 score < 9 . CONCLUSIONS Exposure of patients with at least moderate depressive symptoms to an individually tailored intervention design ed to increase patient engagement in depression care led to increased PCP discussion of suicidal thoughts BACKGROUND Depression and alcohol misuse are among the most prevalent diagnoses in suicide fatalities . The risk posed by these disorders is exacerbated when they co-occur . Limited research has evaluated the effectiveness of common depression and alcohol treatments for the reduction of suicide vulnerability in individuals experiencing comorbidity . METHODS Participants with depressive symptoms and hazardous alcohol use were selected from two r and omised controlled trials . They had received either a brief ( 1 session ) intervention , or depression-focused cognitive behaviour therapy ( CBT ) , alcohol-focused CBT , therapist-delivered integrated CBT , computer-delivered integrated CBT or person-centred therapy ( PCT ) over a 10-week period . Suicidal ideation , hopelessness , depression severity and alcohol consumption were assessed at baseline and 12-month follow-up . RESULTS Three hundred three participants were assessed at baseline and 12 months . Both suicidal ideation and hopelessness were associated with higher severity of depressive symptoms , but not with alcohol consumption . Suicidal ideation did not improve significantly at follow-up , with no differences between treatment conditions . Improvements in hopelessness differed between treatment conditions ; hopelessness improved more in the CBT conditions compared to PCT and in single-focused CBT compared to integrated CBT . LIMITATIONS Low retention rates may have impacted on the reliability of our findings . Combining data from two studies may have result ed in heterogeneity of sample s between conditions . CONCLUSIONS CBT appears to be associated with reductions in hopelessness in people with co-occurring depression and alcohol misuse , even when it is not the focus of treatment . Less consistent results were observed for suicidal ideation . Establishing specific procedures or therapeutic content for clinicians to monitor these outcomes may result in better management of individuals with higher vulnerability for suicide BACKGROUND AND AIMS In the past decade , a large body of research has demonstrated that internet-based interventions can have beneficial effects on depression . However , only a few clinical trials have compared internet-based depression therapy with an equivalent face-to-face treatment . The primary aim of this study was to compare treatment outcomes of an internet-based intervention with a face-to-face intervention for depression in a r and omized non-inferiority trial . METHOD A total of 62 participants suffering from depression were r and omly assigned to the therapist-supported internet-based intervention group ( n=32 ) and to the face-to-face intervention ( n=30 ) . The 8 week interventions were based on cognitive-behavioral therapy principles . Patients in both groups received the same treatment modules in the same chronological order and time-frame . Primary outcome measure was the Beck Depression Inventory-II ( BDI-II ) ; secondary outcome variables were suicidal ideation , anxiety , hopelessness and automatic thoughts . RESULTS The intention-to-treat analysis yielded no significant between-group difference ( online vs. face-to-face group ) for any of the pre- to post-treatment measurements . At post-treatment both treatment conditions revealed significant symptom changes compared to before the intervention . Within group effect sizes for depression in the online group ( d=1.27 ) and the face-to-face group ( d=1.37 ) can be considered large . At 3-month follow-up , results in the online group remained stable . In contrast to this , participants in the face-to-face group showed significantly worsened depressive symptoms three months after termination of treatment ( t=-2.05 , df=19 , p<.05 ) . LIMITATIONS Due to the small sample size , it will be important to evaluate these outcomes in adequately-powered trials . CONCLUSIONS This study shows that an internet-based intervention for depression is equally beneficial to regular face-to-face therapy . However , more long term efficacy , indicated by continued symptom reduction three months after treatment , could be only be found for the online group We conducted a r and omized controlled trial to test whether a Brief Mobile Treatment ( BMT ) intervention could improve outcomes relative to usual care among suicide attempters . The intervention included training in problem solving therapy , meditation , a brief intervention to increase social support as well as advice on alcohol and other drugs , and mobile phone follow-up . The effect of the intervention was measured in terms of a reduction in suicidal ideation , depression and self-harm at Baseline , six and 12 months . A wait-list control group received usual care . A total of 68 participants was recruited from a Sri Lankan hospital following a suicide attempt . Participants who received the intervention were found to achieve significant improvements in reducing suicidal ideation and depression than those receiving usual care . The BMT group also experienced a significant improvement of social support when compared to the control group . However , the BMT group did not demonstrate a significant effect in reducing actual self-harm and most substance use , and differential effects on alcohol use were restricted to men . Although the present study was limited in revealing which component of the intervention was more effective in preventing suicide , it showed its efficacy in reducing suicide as a whole Background : prevention of suicide is one of priority world health . Suicide is one of the preventable causes of death . The aim of this study is evaluation of telephone follow up on suicide reattempt . Material s and Methods : This r and omized controlled clinical trial is a prospect i ve study which has been done in Noor Hospital of Isfahan-Iran , at 2010 . 139 patients who have suicide attempt history divided in one of two groups , r and omly , 70 patients in " treatment as usual ( TAU ) " and 69 patients in " brief interventional control ( BIC ) . Seven telephone contact with BIC group patients have been done " during six months " and two question naires have been filled in each session . The data has been analyzed by descriptive and Chi-square test , under SPSS . Results : No significant differences of suicide reattempt has been found between two groups ( P = 0.18 ) , but significant reduction in frequency of suicidal thoughts ( P = 0.007 ) and increase in hope at life ( P = 0.001 ) was shown in intervention group . Conclusion : Telephones follow up in patients with suicide history decrease suicidal thought frequency " and increase hope in life , significantly OBJECTIVE This pilot r and omized controlled trial examined the effect of an online intervention for college students at risk for suicide , Electronic Bridge to Mental Health Services ( eBridge ) , which included personalized feedback and optional online counseling delivered in accordance with motivational interviewing principles . Primary outcomes were readiness to seek information or talk with family and friends about mental health treatment , readiness to seek mental health treatment , and actual treatment linkage . METHOD Participants were 76 college students ( 45 women , 31 men ; mean age = 22.9 years , SD = 5.0 years ) at a large public university who screened positive for suicide risk , defined by at least 2 of the following : suicidal thoughts , history of suicide attempt , depression , and alcohol abuse . Racial/ethnic self- identification s were primarily Caucasian ( n = 54 ) and Asian ( n = 21 ) . Students were r and omized to eBridge or the control condition ( personalized feedback only , offered in plain report format ) . Outcomes were measured at 2-month follow-up . RESULTS Despite relatively modest engagement in online counseling ( 29 % of students posted ≥1 message ) , students assigned to eBridge reported significantly higher readiness for help-seeking scores , especially readiness to talk to family , talk to friends , and see a mental health professional . Students assigned to eBridge also reported lower stigma levels and were more likely to link to mental health treatment . CONCLUSIONS Findings suggest that offering students personalized feedback and the option of online counseling , using motivational interviewing principles , has a positive impact on students ' readiness to consider and engage in mental health treatment . Further research is warranted to determine the robustness of this effect , the mechanism by which improved readiness and treatment linkage occurs , and the longer term impact on student mental health outcomes BACKGROUND Studies on the effects of interventions in patients who have attempted suicide in China have not reported so far . AIMS To describe the basic situation surrounding the interventions and follow-up of patients who have attempted suicide and to determine whether the interventions would be effective in reducing repeat suicide attempts . METHOD 239 patients who had attempted suicide were evaluated in the emergency departments of four general hospitals . They were r and omized into three groups : cognitive therapy group , telephone intervention group , and control group . Postintervention the participants were evaluated at 3 , 6 , and 12 months separately by the following measurements : a detailed structured question naire , Beck Suicide Ideation Scale ( SIS ) , Hamilton Rating Scale for Depression ( HAMD ) , and a quality -of-life scale . RESULTS After 12 months , the cumulative dropout rate was 69.5 % ( n = 57 ) for the cognitive therapy group , 55.0 % ( n = 44 ) for the telephone intervention group , and 64.9 % ( n = 50 ) for the control group . One patient ( 1.2 % ) in the cognitive therapy group , one patient ( 1.3 % ) in the telephone intervention group , and five patients ( 6.5 % ) in the control group made at least one subsequent suicide attempt . The rates of repeated attempted suicide among the three groups were not significantly different ( χ² = 5.077 , p = .08 ) . Five patients ( 6.1 % ) received cognitive therapy , and 60 patients ( 75.0 % ) received telephone intervention . There were no differences regarding the score of HAMD , a quality -of-life scale , and the rates of subsequent suicide attempt and suicide ideation among the three groups at follow-up . CONCLUSIONS The dropout rates were higher than those reported in developed countries . Most participants in the cognitive therapy group refused to receive cognitive therapy so that the effect of cognitive therapy for these patients can not be evaluated . The participants in the telephone intervention group had good compliance , but the effect of telephone intervention could not be confirmed , so that more studies are needed in the future . Consequently , interventions can not be evaluated accurately in their preventing suicide attempts for patients who have attempted suicide in China at present OBJECTIVE We developed a primary care/Internet-based intervention for adolescents at risk for depression ( CATCH-IT , Competent Adulthood Transition with Cognitive-behavioral , Humanistic and Interpersonal Training ) . This phase II clinical trial compares two forms of primary care provider ( PCP ) engagement ( motivational interview [ MI ] and brief advice [ BA ] ) for adolescents using the Internet program . METHOD ADOLESCENTS SCREENING POSITIVE FOR DEPRESSION WERE RECRUITED FROM PRIMARY CARE PRACTICE S AND R AND OMLY ASSIGNED TO A VERSION OF THE INTERVENTION : PCP MI + Internet program or PCP BA + Internet program . Between-group and within-group comparisons were conducted on depressive disorder outcome measures at baseline and one-year post-enrollment . Regression analyses examined factors predicting declines in depressed mood . RESULTS Both groups demonstrated significant within-group decreases in depressed mood , loneliness , and self-harm ideation . While no between-group differences were noted in depressed mood or depressive disorder measures at one-year , fewer participants in the MI group had experienced a depressive episode . Greater participant automatic negative thoughts and more favorable ratings of a component of the Internet-based training experience predicted declines in depressed mood at one-year . CONCLUSIONS A primary care/Internet-based intervention for depression prevention demonstrated sustained reductions in depressed mood , and , when coupled with motivational interviewing , reduction in the likelihood of being diagnosed with a depressive episode . This tool may help extend the services at the disposal of a primary care provider and can provide a bridge for adolescents at risk for depression prior to referral to mental health specialists Background Suicidal ideation is highly prevalent , but often remains untreated . The Internet can be used to provide accessible interventions . Objective To evaluate the cost-effectiveness of an online , unguided , self-help intervention for reducing suicidal ideation . Methods A total of 236 adults with mild to moderate suicidal thoughts , defined as scores between 1 - 26 on the Beck Scale for Suicide Ideation ( BSS ) , were recruited in the general population and r and omized to the intervention ( n = 116 ) or to a waitlist , information-only , control group ( n = 120 ) . The intervention aim ed to decrease the frequency and intensity of suicidal ideation and consisted of 6 modules based on cognitive behavioral techniques . Participants in both groups had unrestricted access to care as usual . Assessment s took place at baseline and 6 weeks later ( post-test ) . All question naires were self-report and administered via the Internet . Treatment response was defined as a clinical ly significant decrease in suicidal ideation on the BSS . Total per-participant costs encompassed costs of health service uptake , participants ’ out-of-pocket expenses , costs stemming from production losses , and intervention costs . These were expressed in Euros ( € ) for the reference year 2009 . Results At post-test , treatment response was 35.3 % and 20.8 % in the experimental and control conditions , respectively . The incremental effectiveness was 0.35 − 0.21 = 0.15 ( SE 0.06 , P = .01 ) . The annualized incremental costs were −€5039 per participant . Therefore , the mean incremental cost-effectiveness ratio ( ICER ) was estimated to be −€5039/0.15 = −€34,727 after rounding ( US −$41,325 ) for an additional treatment response , indicating annual cost savings per treatment responder . Conclusions This is the first trial to indicate that online self-help to reduce suicidal ideation is feasible , effective , and cost saving . Limitations included reliance on self-report and a short timeframe ( 6 weeks ) . Therefore , replication with a longer follow-up period is recommended |
10,347 | 24,532,137 | This review provides some limited evidence that control of IOP is better with trabeculectomy than viscocanalostomy .
This may reflect surgical difficulties in performing non-penetrating procedures and the need for surgical experience .
Since it is unlikely that better IOP control will be offered by NPFS , but that these techniques offer potential gains for patients in terms of quality of life , we feel that such a trial is likely to be of a non-inferiority design with quality of life measures | BACKGROUND Glaucoma is the second commonest cause of blindness worldwide .
Non-penetrating glaucoma surgeries have been developed as a safer and more acceptable surgical intervention to patients compared to conventional procedures .
OBJECTIVES To compare the effectiveness of non-penetrating trabecular surgery compared with conventional trabeculectomy in people with glaucoma . | Abstract · Background : An investigation was carried out to compare post-operative inflammation following deep sclerectomy with collagen implant ( DSCI ) versus st and ard trabeculectomy . · Methods : In this prospect i ve r and omized study , 46 eyes of 46 Caucasian patients with medically uncontrolled chronic open-angle glaucoma and without previous glaucoma surgery underwent filtering surgery . Twenty-four eyes underwent DSCI . Twenty-two eyes underwent st and ard trabeculectomy . Pre- and post-operative flare , measured using laser flare photometry , were compared between the two groups . · Results : In both groups , the mean anterior chamber flare increased on the first post-operative day , then decreased progressively . DSCI was associated with lower flare measurements post-operatively . The difference was statistically significant up to 1 month post-operatively : 16.3±7.8 vs 72.5±38.9 ( P<0.001 ) at 1 day , 7.8±4.6 vs 44.7±29.2 ( P<0.001 ) at 1 week , 5.9±1.6 vs 7.0±2.8 ( P=0.012 ) at 1 month , 6.4±1.8 vs 6.5±1.9 ( P=0.77 ) at 2 months , 5.9±1.8 vs 6.1±1.6 ( P=0.65 ) at 3 months . · Conclusion : Surgically induced inflammation can be reduced with DSCI . This may be due to the lack of iridectomy , irrigation , and penetration of the anterior chamber . Eyes at increased risk of post-operative inflammation , such as those with uveitic or traumatic glaucoma , may benefit from this procedure . Further studies are needed to evaluate the long-term functional and anatomical outcomes of DSCI Results of trabeculectomy ( TE ) and viscocanalostomy ( VCO ) were compared in a prospect i ve r and omised study in two fellow eyes of 22 consecutive patients with bilateral symmetrical high-tension glaucoma . Rates of overall surgical success with intraocular pressures ( IOP ) ≤ 18 mm Hg with or without medications were 91 for the TE , and 95 for the VCO group after a mean follow-up of 18 months . Complete success rates without medications were 64 and 59 for TE and VCO groups , respectively ( p=0.750 ) . Both procedures significantly reduced IOP , however , IOP course following trabeculectomy was significantly lower ( p=0.026 ) . Rates of complications were not found to be different between the two groups of eyes , except for an apparent – though not significant ( p=0.066 ) – increase in cataract progression with TE . Various types of conjunctival blebs were detected in all eyes with surgical success in both groups , however , diffuse , elevated or multi-cystic functional blebs appeared to be more predominant in eyes with TE , compared to the VCO group in which low-lying , localised blebs had a higher incidence ( p=0.015 ) . Viscocanalostomy was found to be a safe and effective filtration technique in patients with uncomplicated high-tension glaucoma , though IOP decrease was more pronounced with trabeculectomy Purpose : To study the need , the safety and the success rate of collagen implant in eyes that underwent deep sclerectomy , a new non penetrating filtration procedure , we compared the results of deep sclerectomy with ( DSCI ) and without ( DS ) collagen implant . Methods : Of 168 patients ( 168 eyes ) with various types of medically uncontrolled open angle glaucoma , 86 ( 86 eyes ) underwent DSCI , and 82 ( 82 eyes ) underwent DS . Visual acuity , slit lamp examination , intraocular pressure ( IOP ) measurements were performed before surgery and prospect ively at days 1 and 7 and months , 1 , 2 , 3 , 6 , 9 , 12 , 15 , 18 , and 24 after surgery . Deep sclerectomy was performed according to Kozlov 's original technique . The collagen implant drainage device was radially secured in the center of the deep sclerectomy dissection . Results : The mean follow-up period was 9.7 ± 6.5 months for DSCI , and 9.0 ± 4.8 months for DS . The mean preoperative IOP was 26.9 ± 8.8 mmHg for DSCI and 25.8 ± 8.5 mmHg for DS . The mean postoperative IOP and visual acuity were similar between the two groups . Complete and qualified success rates were better when the collagen implant was used ( Log-Rank test : p = 0.0002 and 0.033 for complete and qualified success respectively ) . The need for postoperative glaucoma medications was significantly lower when the collagen implant was used ( 0.2 ± 0.5 versus 0.5 ± 0.7 medication per patient in the DSCI and DS respectively , Student 's t test : p = 0.0038 ) . There was significantly less bleb fibrosis when the collagen implant was used ( 2 % and 11 % in DSCI and DS respectively , p = 0.029 ) . Conclusion : The collagen implant device is safe , increases the success rate of deep sclerectomy , and lowers the need for postoperative glaucoma medications Aims : To compare the long-term effects of low-dosage mitomycin C ( MMC ) in both deep sclerectomy ( DSMMC ) and trabeculectomy ( TPMMC ) on intraocular pressure ( IOP ) . Methods : Analysis of extended follow-up of data from a prospect i ve clinical trial . Forty patients were originally r and omised to undergo either DSMMC ( 19 eyes ) or TPMMC ( 21 eyes ) . Follow-up was performed at postoperative day 1 , weeks 1 , 2 and 3 , as well as months 1 , 3 , 6 , 9 , 12 , 18 , 24 , 36 and 48 . Two- to three-week data were not included in the statistical analysis . Postoperative complications , number of antiglaucoma medications and IOP were recorded at each visit . Complete ( no medications ) and qualified ( with or without medications ) successes were assessed at 2 target IOPs ( ≤21 and ≤17 mm Hg ) and evaluated by Kaplan-Meier curves . Results : At 48 months , the mean IOP ( ± SD ) was 17.6 ± 3.4 and 17.8 ± 3.6 mm Hg in the DSMMC and TPMMC eyes , respectively , a significant reduction from preoperative IOP in each group ( p < 0.0005 ) . Complete success was achieved at the ≤21 mm Hg target IOP in 10 ( 52.6 % ) and 14 ( 66.6 % ) eyes and qualified success in 15 ( 78.9 % ) and 18 ( 85.7 % ) eyes in the DSMMC and TPMMC groups , respectively . There were no differences in the Kaplan-Meier curves . Hypotony and shallow anterior chamber were significantly more frequent in the TPMMC group . Conclusions : Either procedure controlled IOP efficaciously at our endpoint . Low-dosage MMC can be considered a mild enhancement of deep sclerectomy IOP-lowering effect Purpose To compare the intraocular pressure lowering effect and the frequency of postoperative complications in two of the most used filtration surgery techniques : trabeculectomy and non-penetrating deep sclerectomy ( NPDS ) without collagen implants . Methods Thirty-four eyes of 17 patients with medically uncontrolled symmetrical primary open-angle glaucoma were included in the study . One r and omly selected eye per patient had either trabeculectomy or NPDS without collagen implants as the first surgical procedure . The other eye underwent the second filtration surgery technique less than 6 weeks later . Post-operatively , the intraocular pressure ( IOP ) diurnal curves were determined at 1 , 2 , 3 , 6 , 12 and 18 months . The intergroup differences in IOP lowering effect were determined in an analysis of covariance ( ANCOVA ) , with pre-operative IOP as a changing covariate . Kaplan-Meier survival curves were drawn for IOP , and intercurve analysis was performed . Comparisons of the number of post-operative antiglaucomatous medications , as well as of the complication rate , were done by 2 × 2 frequency tables . A p value of less than 0.05 was considered statistically significant . Results There were statistically significant differences in post-operative IOP level between the two groups at 1 , 2 , 3 , 6 , 12 and 18 months , with a lower level in the trabeculectomy group . Using the Kaplan Meier cumulative survival curve , the trabeculectomy patients had a better complete success rate than the NPDS patients at 18 months post-operatively . There were statistically significantly fewer complications in the NPDS group . Conclusion Trabeculectomy lowers the IOP more than the NPDS technique . However , the complication rate seems to be lower in NPDS Purpose : To compare IOP behavior after deep sclerectomy ( DS ) and trabeculectomy with the Crozafon-De Laage Punch ( TP ) , using low-dosage intraoperative mitomycin C ( MMC ) in both techniques . Methods : The study was a prospect i ve r and omized clinical trial . All patients met inclusion and exclusion criteria , and were scheduled for glaucoma surgery . Forty patients were r and omized to undergo either a nonpenetrating DS with MMC ( DSMMC ) ( 19 eyes ) or a TP with MMC ( TPMMC ) ( 21 eyes ) . Postoperative examinations were performed at the 1st day , the 1st , 2nd and 3rd weeks and the 1st , 3rd , 6th , 9th and 12th months . Postoperative complications , number of antiglaucoma medications and the IOP level were checked at each control . Complete success ( without antiglaucoma medications ) and qualified success ( with or without medications ) were assessed at two target IOP levels , namely ≤21 and ≤17 mm Hg in both groups . Moreover , the success rates at ≤21 mm Hg target IOP level were compared with those from previous series of patients who had undergone DS without MMC ( historical control group ) . Results : Data from all eyes were available until the 12th month . The mean preoperative IOP ± SD was 29.6 ± 5.8 mm Hg in DSMMC eyes , 28.0 ± 6.0 in TPMMC eyes ; the mean IOP at the 1st postoperative day was 12.5 ± 4.2 and 13.9 ± 6.5 mm Hg , while at the endpoint the mean IOP was 14.5 ± 4.0 and 16.1 ± 3.8 , respectively , with significant reduction ( p < 0.0005 ) of the preoperative IOP in both groups . Complete success ( ≤21 mm Hg target IOP ) in 15 eyes ( 78.9 % ) of the DSMMC group and in 15 eyes ( 71.4 % ) of the TPMMC group was respectively found , while qualified success was achieved in all the eyes . When a ≤17 mm Hg target IOP was considered , complete success in 12 eyes ( 63.1 % ) and 13 eyes ( 61.9 % ) , and qualified success in 13 eyes ( 68.4 % ) and 15 eyes ( 71.4 % ) were found in the DSMMC and TPMMC groups , respectively . No significant intergroup differences were found in terms of success rate . There is no statistical significance in the Kaplan-Meier cumulative survival curves as for complete and qualified success rate in both surgical groups for a ≤17 mm Hg target IOP ( log rank , p = 0.918 and p = 0.429 , respectively ) . As for the frequency of postoperative complications , hypotony and shallow anterior chamber were significantly more frequent in TPMMC when compared with the DSMMC group . The historical comparison between the DSMMC group and simple DS cases shows no significant difference between the groups , with a mild positive trend in DSMMC when compared with DS eyes . Conclusions : Both techniques , DSMMC and TPMMC , control IOP efficaciously at our endpoint . Our results indicate that low-dosage MMC can be considered a mild enhancement of DS IOP lowering effect without any negative effect on the well-known intra- and postoperative safety of the technique Purpose To compare the intraocular pressure-lowering effect and safety of viscocanalostomy and trabeculectomy with mitomycin C. Methods Twenty-five patients with bilateral primary open-angle glaucoma were enrolled in a prospect i ve clinical study . The eyes of each patient were r and omly assigned to receive viscocanalostomy in one eye and trabeculectomy with mitomycin C in the other eye . The patients were followed up for 12 months . At each visit , best-corrected visual acuity , intraocular pressure , and the appearance of the surgical wound , anterior chamber , and indirect ophthalmoscopy were recorded . Results The mean baseline intraocular pressure was 25.0±2.2 mmHg in viscocanalostomy-treated eyes and 24.8±2.6 mmHg in trabeculectomy-treated eyes . The mean postoperative intraocular pressure was 15.3±1.7 mmHg , 17.1±1.5 mmHg , and 17.1±1.5 mmHg in viscocanalostomy-treated eyes and 11.7±4.4 mmHg , 11.8±4.6 mmHg , and 12.6±4.3 mmHg in trabeculectomy-treated eyes at 3- , 6- and 12-month intervals , respectively . The mean intraocular pressure in viscocanalostomy-treated eyes was significantly higher than that in trabeculectomy-treated eyes at every visit ( P<0.0001 ) . At 12 months , 16 viscocanalostomy-treated eyes ( 64 % ) and 22 trabeculectomy-treated eyes ( 88 % ) achieved an intraocular pressure of less than or equal to 20 mmHg without medication ; there was a significant difference between the two groups ( P=0.0240 ) . There were fewer complications in viscocanalostomy-treated eyes . Complications included four cases of shallow anterior chamber ( 16 % ) and five of hypotony ( 20 % ) in trabeculectomy-treated eyes , against intraoperative microperforation of Descemet 's membrane in one of viscocanalostomy-treated eye ( 4 % ) . Conclusion Trabeculectomy with mitomycin C may be more effective than viscocanalostomy in lowering intraocular pressure in patients with primary open-angle glaucoma , while eyes undergoing viscocanalostomy experience a lower incidence of complications . Further investigation of more cases is needed OBJECTIVE To establish the efficacy and safety of nonpenetrating deep sclerectomy versus trabeculectomy in primary open-angle glaucoma . DESIGN Prospect i ve r and omized trial . PARTICIPANTS Thirty-nine patients ( 78 eyes ) with bilateral primary open angle glaucoma were included in the study . INTERVENTION Eyes were r and omly assigned to receive deep sclerectomy in one eye and trabeculectomy in the other eye . MAIN OUTCOME MEASURES Mean intraocular pressure ( IOP ) , postoperative medications , visual acuity , success rate , and complications . RESULTS At 12 months , mean IOP reduction was 12.3 + /- 4.2 ( sclerectomy ) versus 14.1 + /- 6.4 mmHg ( trabeculectomy ) ( P = 0.15 ) , and an IOP < /= 21 mmHg was achieved in 36 ( 92.3 % ) and 37 eyes ( 94.9 % ) ( P = 0.9 ) , respectively . Complications included three ( 7.7 % ) flat/shallow anterior chambers and one ( 2.6 % ) hypotony ( trabeculectomy ) , whereas internal iris incarceration was encountered in two eyes ( 5.1 % ) ( sclerectomy ) . CONCLUSIONS Deep sclerectomy may provide comparable IOP reduction with fewer complications in management of primary open angle glaucoma Purpose To assess the intraocular pressure-lowering efficacy and the postoperative complication profile of viscocanalostomy versus trabeculectomy . Patients and Methods Sixty eyes of 60 patients with medically uncontrolled open-angle glaucoma were r and omized either to the viscocanalostomy or to the trabeculectomy group of the trial . Viscocanalostomy was performed according to Stegmann 's technique using high-molecular-weight sodium hyaluronate to fill the ostia of the Schlemm canal . For trabeculectomy , a modified Cairns-trabeculectomy was performed . Examinations were performed before surgery and postoperatively daily for 1 week . Follow-up visits were scheduled 1 , 6 , and 12 months after surgery . Results The mean ( SD ) preoperative intraocular pressure was 27.1 ( 7.1 ) mm Hg for all patients enrolled . One day after surgery , mean ( SD ) intraocular pressure was 15.9 ( 5.2 ) for the trabeculectomy group ( P < 0.001 ) and 15.7 ( 3.6 ) for the viscocanalostomy group ( P < 0.001 ) , respectively . The success rate , defined as an intraocular pressure lower than 22 mm Hg without medication , was 56.7 % in the trabeculectomy group and 30 % in the viscocanalostomy group at 12 months postoperatively ( P = 0.041 ) . The number of postoperative complications was lower in the viscocanalostomy group than in the trabeculectomy group . Conclusions In eyes with open-angle glaucoma , viscocanalostomy is less effective in reducing intraocular pressure than st and ard filtering surgery . However , postoperative complications are more frequent after filtering surgery PURPOSE To study the clinical effectiveness of viscocanalostomy in a population of black African patients with open-angle glaucoma that was uncontrolled on medical treatment . SETTING Department of Ophthalmology , Medical University of Southern Africa , Medunsa , South Africa . METHODS In this prospect i ve study viscocanalostomy was performed in 214 eyes of 157 black African patients with open-angle glaucoma that was poorly controlled by medical therapy . The procedure involves the production of superficial and deep scleral flaps . The deep flap is disserted to the plane of Schlemm 's canal . From this plane , an intact window in Descemet 's membrane is created by gentle pressure at the level of Schwalbe 's line using a cellulose sponge . Aqueous humor diffuses through this window into a subscleral space ( lake ) . Reflection of the inner flap unroofs Schlemm 's canal , creating a trough leading to 2 entrances into Schlemm 's canal ( surgical ostia ) . A delicate cannula is introduced into the entrance of Schlemm 's canal left and right and high-viscosity sodium hyaluronate is gently injected into the canal for 4 to 6 mm . The deeper scleral flap is excised ( deep sclerectomy ) and the superficial flap is sutured securely using 5 , 11 - 0 polyester fiber ( Mersilene ) sutures . High-viscosity sodium hyaluronate is then injected into the subscleral lake to act as a physical barrier to fibrinogen migration postoperatively . RESULTS Postoperative intraocular pressure ( IOP ) of 22 mm Hg or less was achieved without medical therapy in 82.7 % of eyes . If a beta blocker was added to the cases not achieving 22 mm Hg or less postoperatively , the success rate increased to 89.0 % . The average follow-up was 35 months ( range 6 to 64 months ) . CONCLUSION Viscocanalostomy produced an encouraging long-term reduction in the IOP of black African patients with glaucoma who would otherwise have had a poor prognosis PURPOSE To compare the effectiveness and safety of viscocanalostomy and trabeculectomy in adults with uncontrolled open-angle glaucoma . DESIGN Single-masked , parallel-group , prospect i ve , r and omized 24-month trial , with 90 % power to detect a clinical ly important difference between groups . PARTICIPANTS Fifty consecutive patients ( 50 eyes ) with primary open-angle or pseudoexfoliative glaucoma . INTERVENTION Eyes were assigned r and omly to either viscocanalostomy ( group 1 ) or trabeculectomy ( group 2 ) with no intraoperative antifibrotics in the study eye . In group 1 , no further intervention was allowed , whereas trabeculectomy eyes could receive subconjunctival 5-fluorouracil ( 5-FU ) injections or laser suture lysis after surgery . MAIN OUTCOME MEASURES Success rate based on intraocular pressure ( IOP ) , visual acuity , discomfort , and other complications . RESULTS At the end of the 24-month follow-up , IOP of 21 mmHg or less and more than 6 mmHg was achieved in 76 % in group 1 ( n = 19 ) and in 80 % in group 2 ( n = 20 ; log-rank P = 0.60 ) ; an IOP between 6 and 16 mmHg was obtained in 56 % in group 1 ( n = 14 ) and in 72 % in group 2 ( n = 18 ; log-rank P = 0.17 ; Kaplan-Meier cumulative probability of success ) . Complications of viscocanalostomy included one intraoperative conversion into trabeculectomy ; microruptures in Descemet 's membrane in five eyes ; three cases of iris incarceration in the Decemet 's window , two of which caused early failure of the procedure requiring reoperation ; and a 1-mm to 2-mm transient self-resolving hyphema in three cases . Complications of trabeculectomy included one case of postoperative bleb bleeding with early transient IOP spike ; one early hyphema ; five cases of postoperative hypotony , two of which had a positive Seidel test from the conjunctival suture ; three cases of transient choroidal detachment , two of which had shallow anterior chamber . No patient required reoperation . Two eyes required argon laser suture lysis , and nine underwent one or more 5-FU injections , which caused punctate keratopathy in three eyes . CONCLUSIONS Viscocanalostomy is an effective IOP-lowering procedure in white adults affected by open-angle glaucoma . Trabeculectomy with postoperative 5-FU can probably provides lower IOPs but , with more numerous complications , greater discomfort , and more intensive postoperative management Aims The purpose of this r and omized clinical trial was to compare the effectiveness and safety of viscocanalostomy ( visco ) with trabeculectomy ( trab ) in the management of primary open angle glaucoma ( POAG ) . Methods Patients were r and omized to have a viscocanalostomy ( 25 eyes ) or a trabeculectomy ( 25 eyes ) performed by one surgeon ( TDM ) and followed up prospect ively . Patients were examined preoperatively , at day 1 , day 3 if required , day 6 , week 2 and thereafter as near as possible to 1 , 3 , 6 , 12 , 18 , 24 , 30 , 36 , 48 , 54 , and 60 months . We recorded intraocular pressure ( IOP ) , presence or absence of any complications , presence and description of any bleb , visual acuity with glasses , and full examinations as routine to monitor any progression of the glaucoma . Bleb interventions including needling and antimetabolites were allowed and recorded in both groups . YAG laser goniopuncture was allowed in the viscocanalostomy group . Results Mean follow-up was 40 months ( SD 15 ) , with a range from 6 to 60 months . Forty-two percent ( n=10 ) of the patients in the trabeculectomy group had a successful outcome ( IOP<18 mm Hg with no treatment ) at last follow-up visit , compared to 21 % ( n=5 ) in the viscocanalostomy group . IOP was lower in the trab group with differences in IOP being statistically significant at month 12 ( P=<0.001 ) , 24 ( P=<0.001 ) , 30 ( P=0.030 ) , 36 ( P=<0.001 ) , and 48 ( P=0.018 ) . The trabeculectomy group required less postoperative topical IOP-lowering medication ( P=0.011 ) . Conclusion In this study , we found trabeculectomy to be more effective at lowering IOP than viscocanalostomy in POAG patients Objective To study and compare the efficacy and safety of nonpenetrating very deep sclerectomy ( NPVDS ) with the use of hyaluronic acid implant ( SKGEL ) to trabeculectomy ( TB ) in patients with with medically uncontrolled glaucoma . Methods Prospect i ve , controlled study of patients with open-angle glaucoma was design ed . Seventy-eight eyes of 68 patients with medically uncontrolled glaucoma were assigned either to the NPVDS or to the TB group of trial . Examinations were applied before and 7 days , 1 , 3 , 6 , 12 , 18 , and 24 months after surgery . Main outcome measureBest-corrected logMAR visual acuity , intraocular pressure , number of additional procedures , antiglaucoma medications , number of complications . Results At 24 months , success rate defined as IOP ≤ 21 mmHg with medication and additional procedures in NPVDS group was 92.31 % , and 94.88 % in control group ( p = 0.64 ) . There was no statistically significant difference between intraocular pressure in NPVDS ( 14.56 ± 4.07 mmHg ) and control ( TB ) ( 15.38 ± 3.38 mmHg ) group ( p = 0.34 ) . Number of glaucoma mediations decreased from 2.18 ± 0.56 to 0.54 ± 0.56 in NPVDS and from 2.28 ± 1.41 to 0.61 ± 0.03 in TB group ( p = 0.71 ) . Early and late postoperative complications included two cases of hyphema , two of choroidal detachment , two of filtering bleb fibrosis , four of cataract progression in the NPVDS group ; and five cases of hyphema , four of choroidal detachment , one of filtering bleb fibrosis , one of blebitis , and 12 of cataract progression in the control group . Conclusions NPVDS is an effective surgical option for patients with medically uncontrolled glaucoma . NPVDS is associated with a lower risk of complications , and in particular cataract progression , compared to TB.Application to clinical practice NPVDS is a modification of NPDS devised for patients with medically uncontrolled open-angle glaucoma Purpose To compare the intraocular pressure (IOP)-lowering effect and complication rate of nonpenetrating deep sclerectomy ( NPDS ) with reticulated hyaluronic acid ( SK-GEL ® ) scleral implant versus traditional punch trabeculectomy ( PT ) in the management of primary open angle glaucoma ( POAG ) . Methods Prospect i ve , r and omized comparative study including 93 patients with uncontrolled POAG . Group 1 ( 43 eyes ) underwent NPDS with SK-GEL ® scleral implant ; Group 2 ( 50 eyes ) underwent PT Mitomycin C ( 0.2 mg/mL ) was applied intraoperatively in both techniques . Study follow-up evaluations were conducted at 36 and 48 months . Complete success indicated the achievement of the target IOP without antiglaucoma medications , while qualified success indicated the same goal with medications . These categories were assessed at two target IOP levels , < 21 mmHg and < 18 mmHg . Results At 36 months for complete and qualified success with a < 21 and < 18 mmHg target IOP , no significant differences were noted between the two groups . At 48 months postprocedure when a < 21 mmHg IOP target was considered , the rate of eyes that achieved complete success was 51.1 % in the NPDS group versus 72 % in the PT group ( p<0.05 ) . As for the < 18 mmHg IOP target , the rate of eyes that achieved complete success was 32.5 % in the NPDS group versus 44 % in the PT group ( p<0.05 ) . Complications occurred significantly more frequently after PT than after NPDS . Conclusions The IOP-lowering effects of the two procedures were comparable at 36 months . At 48 months PT showed a significantly higher rate of complete success compared with NPDS . Complications were more frequent after PT than after NPDS Purpose : To compare the efficacy and safety of viscocanalostomy and trabeculectomy in patients with primary open‐angle glaucoma ( POAG ) . Setting : Department of Ophthalmology , Ankara Education and Research Hospital , Ankara , Turkey . Methods : In this prospect i ve r and omized trial , 50 eyes of 50 patients with medically uncontrolled POAG were r and omized to have a trabeculectomy ( 25 eyes ) or a viscocanalostomy ( 25 eyes ) . Visual acuity , intraocular pressure ( IOP ) , and slitlamp examinations were performed before surgery and 1 day , 1 week , 1 , 3 , and 6 months , and 1 , 2 , and 3 years postoperatively . Results : At 3 years , the mean IOP was 16.0 mm Hg ± 7.07 ( SD ) in the trabeculectomy group and 17.8 ± 4.6 mm Hg in the viscocanalostomy group ( P = .694 ) . Complete success ( IOP 6 to 21 mm Hg without medication ) was achieved in 66.2 % of eyes at 6 months and 55.1 % at 3 years in the trabeculectomy group and in 52.9 % and 35.3 % , respectively , in the viscocanalostomy group ( P>.05 ) . Qualified success ( IOP 6 to 21 mm Hg with medication ) was achieved in 95.8 % of eyes at 6 months and 79.2 % at 3 years in the trabeculectomy group and in 90.7 % and 73.9 % , respectively , in the viscocanalostomy group ( P>.05 ) . Postoperative hypotony and cataract formation occurred more frequently in the trabeculectomy group than in the viscocanalostomy group ( P = .002 ) . Conclusions : Primary trabeculectomy lowered IOP more than viscocanalostomy in POAG patients . However , the complication rate was lower in the viscocanalostomy group OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) PURPOSE To compare viscocanalostomy , a nonpenetrating procedure for glaucoma treatment , with trabeculectomy . DESIGN R and omized controlled trial . PARTICIPANTS Twenty white subjects ( 20 eyes ) with open-angle glaucoma with no history of surgery were enrolled . METHODS Ten subjects were r and omly assigned to viscocanalostomy according to Stegmann 's technique and 10 subjects to a modified Cairns trabeculectomy . A complete ophthalmologic examination was performed the day before surgery and postoperatively . Further visits were scheduled monthly for 6 to 8 months after surgery . MAIN OUTCOME MEASURES Success was defined as intraocular pressure ( IOP ) between 7 and 20 mmHg , with no medication . RESULTS After a mean follow-up of 6 months ( range , 6 - 8 months ) , success was obtained in 5 of 10 cases in the trabeculectomy group and in no case in the viscocanalostomy group . With Kaplan-Meier 's method , subjects with viscocanalostomy showed shorter postoperative IOP-reduction periods than subjects undergoing trabeculectomy . CONCLUSIONS According to the results of this short-term study , trabeculectomy was more effective than viscocanalostomy in lowering IOP in glaucomatous eyes of white patients OBJECTIVE To compare the clinical outcome of trabeculectomy with viscocanalostomy in patients with primary open angle glaucoma ( POAG ) . METHODS 100 patients ( 100 eyes ) with uncontrolled POAG were r and omly assigned to either trabeculectomy group ( 50 eyes ) or viscocanalostomy ( VCO ) group ( 50 eyes ) and followed up for average 28 months . Intraocular pressure ( IOP ) was measured with a non-contact Topcon CT80 tonometer . RESULTS At 1 month after operation , IOP was ( 11.22 + /- 4.34 ) and ( 12.35 + /- 3.79 ) mmHg ( 1 mmHg = 0.133 kPa , n = 50 ) in the eyes undergoing VCO or trabeculectomy surgery , respectively . The complete success rate ( IOP < 21 mmHg without antiglaucoma medications ) was 98.0 % in both groups . There was no significant difference in IOP and complete success rate between both groups . At 12 months , IOP in VCO group was significantly ( P < 0.05 ) lower ( 14.50 + /- 3.22 ) than that in trabeculectomy group ( 16.58 + /- 4.73 ) mmHg , while the complete success rate in VCO group ( 87.5 % ) was significantly higher ( P < 0.05 ) than that in trabeculectomy group ( 70.0 % ) . The early transient complications such as shallow anterior chamber and encysted blebs were significantly ( P < 0.01 ) more common in trabeculectomy group than in VCO group . CONCLUSIONS VCO appears to have long term advantages over trabeculectomy in terms of complete success rate , IOP control , and less early transient postoperative complications in POAG |
10,348 | 17,577,007 | These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects .
Had the investigators terminated the trial in accordance with their stopping rule , subsequent patients with leukemia may have experienced the toxicity of an additional course of chemotherapy without benefit . | Stopping r and omized trials early because of an apparent benefit is a growing phenomenon .
A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) .
To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment .
If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ?
In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances .
If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change .
Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical .
Table .
Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading .
The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment .
Social or Scientific Value and Favorable RiskBenefit Ratio It is underst and able that investigators focus their ethical obligations on research participants .
Such focus , however , risks neglecting obligations to society .
The tendency of truncated trials to overestimate the effect of a treatment on the end point that result ed in trial truncation and to yield insufficient data about other important outcomes endangers the wider community to whom the results will be applied ( 6 ) .
Harm result ing from the misleading findings of truncated trials can be compounded if the findings influence the recommendations of clinical practice guideline panels .
However , as we have pointed out , the astute clinician or patient may remain skeptical about a treatment 's apparent benefits if the findings come from a truncated trial .
Unfortunately , many clinicians and even more patients probably will not have the knowledge and underst and ing to appropriately interpret the results .
Disclosing interim results to study participants may therefore prove misleading .
Furthermore , if investigators were to continue a trial after informing patients of the interim results , patients would be unblinded and may cross over or leave the trial .
These behaviors create problems in interpreting trial results by further weakening inferences about the efficacy and safety of the intervention and compromising the ethical requirement of scientific validity .
Finally , stopping a trial early does not guarantee that current and potential trial participants will receive the apparently beneficial treatment ( assuming that one believes they should ) .
Studies of dissemination of new treatments reveal that long delays , such as those between reports of r and omized trials and recommendations of experts in review articles and textbooks , are common ( 14 ) . | OBJECTIVE To assess whether a pragmatic policy of perioperative beta-blockade , with metoprolol , reduced the 30-day cardiovascular morbidity and mortality and reduced the length of hospital stay in average patients undergoing infrarenal vascular surgery . METHODS This was a double-blind r and omized placebo-controlled trial that occurred in vascular surgical units in four UK hospitals . Participants were 103 patients without previous myocardial infa rct ion who had infrarenal vascular surgery between July 2001 and March 2004 . Interventions were oral metoprolol ( 50 mg twice daily , supplemented by intravenous doses when necessary ) or placebo from admission until 7 days after surgery . Holter monitors were kept in place for 72 hours after surgery . RESULTS Eighty men and 23 women ( median age , 73 years ) were r and omized , 55 to metoprolol and 48 to placebo , and 97 ( 94 % ) underwent surgery during the trial . The most common operations were aortic aneurysm repair ( 38 % ) and distal bypass ( 29 % ) . Intraoperative inotropic support was required in 64 % and 92 % of patients in the placebo and metoprolol groups , respectively . Within 30 days , cardiovascular events occurred in 32 patients , including myocardial infa rct ion ( 8 % ) , unstable angina ( 9 % ) , ventricular tachycardia ( 19 % ) , and stroke ( 1 % ) . Four ( 4 % ) deaths were reported . Cardiovascular events occurred in 15 ( 34 % ) and 17 ( 32 % ) patients in the placebo and metoprolol groups , respectively ( unadjusted relative risk , 0.94 ; 95 % confidence interval , 0.53 - 1.66 ; adjusted [ for age , sex , statin use , and aortic cross-clamping ] relative risk , 0.87 ; 95 % confidence interval , 0.48 - 1.55 ) . Time from operation to discharge was reduced from a median of 12 days ( 95 % confidence interval , 9 - 19 days ) in the placebo group to 10 days ( 95 % confidence interval , 8 - 12 days ) in the metoprolol group ( adjusted hazard ratio , 1.71 ; 95 % confidence interval , 1.09 - 2.66 ; P < .02 ) . CONCLUSIONS Myocardial ischemia was evident in a high proportion ( one third ) of the patients after surgery . A pragmatic regimen of perioperative beta-blockade with metoprolol did not seem to reduce 30-day cardiovascular events , but it did decrease the time from surgery to discharge BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects Abstract Objectives To evaluate the long term effects of perioperative β blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery . Design R and omised placebo controlled and blinded multicentre trial . Analyses were by intention to treat . Setting University anaesthesia and surgical centres and one coordinating centre . Participants 921 patients aged > 39 scheduled for major non-cardiac surgery . Interventions 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days . Main outcome measures The composite primary outcome measure was time to all cause mortality , acute myocardial infa rct ion , unstable angina , or congestive heart failure . Secondary outcome measures were time to all cause mortality , cardiac mortality , and non-fatal cardiac morbidity . Results Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group . Metoprolol significantly reduced the mean heart rate by 11 % ( 95 % confidence interval 9 % to 13 % ) and mean blood pressure by 3 % ( 1 % to 5 % ) . The primary outcome occurred in 99 of 462 patients in the metoprolol group ( 21 % ) and 93 of 459 patients in the placebo group ( 20 % ) ( hazard ratio 1.06 , 0.80 to 1.41 ) during a median follow-up of 18 months ( range 6 - 30 ) . All cause mortality was 16 % ( 74/462 ) in the metoprolol group and 16 % ( 72/459 ) in the placebo group ( 1.03 , 0.74 to 1.42 ) . The difference in risk for the proportion of patients with serious adverse events was 2.4 % ( − 0.8 % to 5.6 % ) . Conclusions Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes . Confidence intervals , however , were wide , and the issue needs re assessment . Trial registration Current Controlled Trials IS RCT N58485613 [ controlled-trials.com OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P < 0.05 ) . When analyzed by clinic , each of the active intervention groups differed significantly from the control clinics ( P < 0.05 ) . The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI < or ≥ 25 kg/m2 ) . In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P < 0.03 ) , 46 % ( P < 0.0005 ) , and 42 % ( P < 0.005 ) reductions in risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT The preliminary results of the twelfth Medical Research Council acute myeloid leukemia trial show no evidence of a survival advantage for five courses of therapy compared to four courses in a r and omized comparison involving 1078 patients ( hazard ratio 1.09 , 95 % confidence interval [ CI ] 0.87 - 1.37 , p=0.4 ) . However , the data presented to the independent data monitoring and ethics committee ( DMEC ) at both its review s in 1998 suggested large benefits for the additional course with hazard ratios of 0.47 and 0.55 ( 95 % CIs 0.29 - 0.77 and 0.38 - 0.80 , p=0.003 and p=0.002 , respectively ) . Despite these highly significant findings , the DMEC did not recommend closure of the r and omization , a decision vindicated by the subsequent reversion to a null result . The main reason for not closing the r and omization was that the treatment effects observed in 1998 ( 53 % and 45 % reductions in the odds of death ) were considered too large to be clinical ly plausible , despite the p-values associated with them . Investigations have not identified any clinical explanations , such as different types of patients in the early and later parts of the trial , to explain the loss of benefit as the trial progressed . Thus , the most likely current explanation for the large benefit observed early on is the play of chance . Lessons to be learned from this example are that : fixed stopping rules based on some predetermined p-value should not be used and the decision to close a r and omization or not should take account of other factors such as the medical plausibility of the magnitude of the treatment effect ; chance effects do occur and happen more frequently than many clinicians realize ; it is important that DMEC members are experienced in the interpretation of clinical trial evidence and aware of the dangers of early stopping without wholly convincing evidence 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 A r and omized , double-blind study to determine the effect of intramuscular vitamin E on mortality and intracranial hemorrhage ( ICH ) was performed . One hundred forty-nine neonates with birth weights less than or equal to 1000 g and less than or equal to 24 hours of age were grouped by weight ( 501 to 750 g and 751 to 1000 g ) and r and omized to treatment or control . The treatment group received intramuscular injections of vitamin E ( dl-alpha-tocopherol ) on days 1 , 2 , 4 , and 6 of life . The control group received intramuscular injections of placebo on the same schedule . All neonates initially received oral vitamin E ( 100 mg/kg/day dl-alpha-tocopheryl acetate ) , which was subsequently adjusted to keep serum levels at 0.5 to 3.5 mg/dL. Ultrasonographic examinations of the head were performed as possible on days 1 , 5 to 7 , and 12 to 14 . Hemorrhage was defined as mild if less than or equal to grade II ICH , or severe if grade III or IV . No significant differences in neonatal or total hospital mortality between groups were found . However , all ICH , as well as severe ICH , were significantly less in the vitamin E-treated 501 to 750-g subgroup ( all ICH : 60 % vs 29 % ; severe ICH : 32 % vs 4 % ) . When survivors were analyzed separately , a significant decrease in severe ICH was seen in the vitamin E-treated neonates ( 25 % vs 5 % ) . Necrotizing enterocolitis and sepsis did not occur more frequently in the neonates treated with intramuscular injections of vitamin E. Other than two cases of mild in duration at injection sites , no deleterious side effects of treatment were identified . Vitamin E may have a role in the prevention of severe ICH in premature neonates weighing between 501 and 750 BACKGROUND Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery . METHODS We performed a r and omized , multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infa rct ion within 30 days after major vascular surgery in patients at high risk for these events . High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography . Eligible patients were r and omly assigned to receive st and ard perioperative care or st and ard care plus perioperative beta-blockade with bisoprolol . RESULTS A total of 1351 patients were screened , and 846 were found to have one or more cardiac risk factors . Of these 846 patients , 173 had positive results on dobutamine echocardiography . Fifty-nine patients were r and omly assigned to receive bisoprolol , and 53 to receive st and ard care . Fifty-three patients were excluded from r and omization because they were already taking a beta-blocker , and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing . Two patients in the bisoprolol group died of cardiac causes ( 3.4 percent ) , as compared with nine patients in the st and ard-care group ( 17 percent , P=0.02 ) . Nonfatal myocardial infa rct ion occurred in nine patients given st and ard care only ( 17 percent ) and in none of those given st and ard care plus bisoprolol ( P<0.001 ) . Thus , the primary study end point of death from cardiac causes or nonfatal myocardial infa rct ion occurred in 2 patients in the bisoprolol group ( 3.4 percent ) and 18 patients in the st and ard-care group ( 34 percent , P<0.001 ) . CONCLUSIONS Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infa rct ion in high-risk patients who are undergoing major vascular surgery |
10,349 | 10,796,446 | There are no convincing data showing fluspirilene decanoate 's advantage over oral chlorpromazine or other depot antipsychotics .
REVIEW ER 'S CONCLUSIONS The total numbers in each comparison were small and there were no clear differences demonstrated between fluspirilene and oral medication or other depots . | BACKGROUND Anti-psychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders .
Long-acting depot injections of drugs such as fluspirilene are extensively used as a means of long-term maintenance treatment .
OBJECTIVES To assess the effects of depot fluspirilene versus placebo , oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical , social and economic outcomes . | While r and omized clinical trials remain the " gold st and ard " for comparisons of treatment efficacy , conventional r and omized trials may not reflect the relative effectiveness of treatments under " real world " conditions . Observational data more closely reflect the conditions of actual practice , but are often limited in clinical detail and subject to bias in selection of treatments . The authors use available data on the cost-effectiveness of new antidepressant drugs to illustrate the limitations of these methods . Modifications to the traditional r and omized trial may allow more accurate assessment of effectiveness in everyday practice . The authors describe the design of such a " real world " r and omized trial comparing newer antidepressants with older alternatives 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 A 4-week double-blind controlled clinical trial was carried out in which fluspirilene , an injectable diphenylbutylpiperidine neuroleptic given weekly , was compared to chlorpromazine in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation . Similar therapeutic improvement was obtained with both drugs , but men needed a significantly higher mean dose of fluspirilene ( 23 mg/week ) than women ( 13 mg/week ) . Fluspirilene induced more parkinsonism than chlorpromazine , but less drowsiness , dizziness , and dry mouth . The difference between the sexes in the potency of fluspirilene and its greater potential to induce parkinsonism may be related to its lesser presynaptic and D1-dopamine receptor blocking properties . The low incidence of autonomic side effects confirms the relative specificity of fluspirilene for dopamine receptors Five depot neuroleptics ( fluphenazinedeconoate , fluspirilene , pipothiazinepalmitate , penfluridol and perphenazine-enanthate ) were compared based on clinical trials in subacute and chronic schizophrenic patients . The psychopathological symptoms were documented by means of the AMP-system . Statistical analyses showed several differences between the effects of the five substances . The AMP-system proved a useful instrument to differentiate similar drugs BACKGROUND An increasing number of case reports indicate a superior therapeutic response of catatonialike symptoms , such as severe psychomotor disturbance and mutism , associated with psychiatric disorder to the benzodiazepine lorazepam ( LO ) . Equivocal results , however , are also reported with regard to other benzodiazepines for the treatment of this syndrome . The purpose of this study was to compare the effects of LO and oxazepam ( OX ) , benzodiazepines with comparable pharmacokinetics , on psychomotor retardation and mutism associated with psychiatric disorder . METHODS Twenty-one hospitalized patients with severe psychomotor retardation and mutism were treated with 2 mg LO and 60 mg OX in a double-blind crossover study design . RESULTS Both benzodiazepines significantly reduced psychomotor symptoms . When administered for the first time , 4 of 7 patients with LO and 6 of 10 patients with OX improved at least 50 % on visual analog scale ( VAS ) rating . Reduction in symptoms was significant with LO and OX treatment on either day of treatment . The second time , however , LO was significantly better compared with OX in alleviating the target symptoms . CONCLUSIONS Both OX and LO are effective for the treatment of psychomotor retardation . Thus , the beneficial effect of LO on psychomotor retardation and mutism is not a unique pharmacodynamic property but more likely due to its pharmacokinetic profile . The differential effect of the two benzodiazepines on the second day of treatment warrants further clarification . Several hypotheses are evaluated Little is known about patient compliance with topical aural antibiotic regimens . The compliance of 50 patients with unilateral otitis externa attending an otolaryngology clinic was studied by comparing the weight of dispensed topical ear preparations before and after completion of a 7-day-course of treatment . A st and ard was obtained from controlled administration of the preparation under laboratory conditions and the performance of different delivery systems evaluated . Thirty-seven patients re-attended for review with their medication . A total of 34 of 50 patients entering the study ( 70 % ) satisfied conventional criteria for compliance . However , over-use of preparations was common and stricter criteria are proposed and applied . Compliance was significantly increased when someone other than the patient administered the preparation 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 A double-blind placebo trial of fluphenazine decanoate , a long-acting phenothiazine , was carried out to determine its value in maintenance therapy of chronic schizophrenic out patients already established on the drug for a minimum period of eight weeks . In low doses it was significantly more effective than placebo in preventing relapse and admission to hospital . Relapse was accompanied by a resurgence of specifically schizophrenic symptoms and by an increase in abnormalities described by the relatives . There was no difference between the experimental and control groups in the treatment required for depression . The group on active medication required more treatment for Parkinsonism , but this difference did not reach statistical significance . In the context of a well-run special clinic for outpatient follow-up of chronic schizophrenic patients these results confirm the usefulness of long-acting fluphenazine . By inference , the benefit of this treatment highlights the need for adequate community services to deal with the residual chronic disabilities which are characteristic of these patients OBJECTIVE To assess the method ologic quality of approaches used to allocate participants to comparison groups in r and omized controlled trials from one medical specialty . DESIGN Survey of published , parallel group r and omized controlled trials . DATA SOURCES All 206 reports with allocation described as r and omized from the 1990 and 1991 volumes of four journals of obstetrics and gynecology . MAIN OUTCOME MEASURES Direct and indirect measures of the adequacy of r and omization and baseline comparisons . RESULTS Only 32 % of the reports described an adequate method for generating a sequence of r and om numbers , and only 23 % contained information showing that steps had been taken to conceal assignment until the point of treatment allocation . A mere 9 % described both sequence generation and allocation concealment . In reports of trials that had apparently used unrestricted r and omization , the differences in sample sizes between treatment and control groups were much smaller than would be expected due to chance . In reports of trials in which hypothesis tests had been used to compare baseline characteristics , only 2 % of reported test results were statistically significant , lower than the expected rate of 5 % . CONCLUSIONS Proper r and omization is required to generate unbiased comparison groups in controlled trials , yet the reports in these journals usually provided inadequate or unacceptable information on treatment allocation . Additional analyses suggest that nonr and om manipulation of comparison groups and selective reporting of baseline comparisons may have occurred 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 Fifty chronic schizophrenics were r and omly assigned to a 16‐week treatment either with fluspirilene or with fluphenazine decanoate . The aim of the study was to compare the antipsychotic action and the side effects of the two neuroleptics . Fluphenazine decanoate caused more side effects and the difference between the two groups was statistically significant in the items tremor , severe extrapyramidal effects and parkinsonism . More patients in the fluspirilene group ( nine patients ) compared with only three in the fluphenazine decanoate group remained free of side effects during the whole trial . Judged from the BPRS fluspirilene proved an equally potent neuroleptic with fluphenazine decanoate although statistically significant improvement has been obtained in more items of the scale in the fluspirilene group . The improvement in the NOSIE‐30 was much more clear in the fluspirilene group . Although Clinical Global Impressions of the investigators and the nursing personnel favored fluspirilene , the differences between the two groups were not statistically significant 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 This study is a part of a multicentric study of some new long-acting psychotropic drugs and their possible application in the maintenance treatment of patients suffering from chronic schizophrenic syndromes ( Perris , ( Ed . ) 1974 ) . The present article deals with a controlled trial of fluspirilene and fluphenazine enanthate carried out simultaneously at Department I1 of the Lillhagen Psychiatric Hospital in Gothenburg ' " , at the Restad Psychiatric Hospital in Vanersborg ' > ) ) , and at the Umedal Psychiatric Hospital in Umeb'+ * ) . The social structure of the hospitals involved in the trial has been investigated in separate studies reported in detail elsewhere ( Malm , Perris , R a p p & Roma'n 1974 a , b ; Perris , Rapp G Romrin 1974 ) . Fluspirilene , 8-[~,~-bis(p-fluorophenyl)butyl]-l-phenyl-l,~,8-triazaspiro ( 4,5 ) decan-4-on is a new compound synthesized at the Janssen Pharmaceutica Research Laboratories and related to the butyrophenones . Fig. 1 shows its chemical structure . The substance is a yellowish-white amorphous or crystalline solid , almost insoluble in water . It is prepared as a micronized suspension in water for intramuscular administration . Pharmacological ( lanssen et al. 1970 , Heykants 1969 ) and preliminary clinical investigations ( Haase et al. 1968 , Sterkmans et al. 1968 , Zmmich et al. 1970 , Knaack 1969 ) have shown fluspirilene to be a highly potent neuroleptic drug with a duration of action ranging from 6 to 15 days ( Madalena 1968 ) . Few side effects , mainly of the extrapyramidal type have been described . No toxic reactions have been reported . Peak effects usually occur |
10,350 | 22,761,122 | The systematic review of seven RCTs and one observational study has demonstrated that in patients who have undergone cardiac surgery , a more consistent and sustained diuresis is produced by a continuous infusion of furosemide compared with intermittent bolus doses of furosemide .
We conclude that continuous furosemide infusion in the perioperative period promotes a gentle and sustained diuresis in cardiac surgery patients .
The evidence supporting the benefit of this strategy in terms of reducing the need for RRT is weak .
At the same time , current best available evidence , albeit from small RCTs , suggests that the timely introduction of continuous furosemide infusion does not increase the incidence of renal impairment after cardiac surgery | The question addressed was ' Does perioperative furosemide usage reduce the need for renal replacement therapy in cardiac surgery patients ? ' | Objective : To compare the amount of furosemide needed to fulfil defined criteria for renal output if given intermittently or as a continuous infusion and to compare the effect of these two regimens on hemodynamic variables and urine electrolyte concentrations . Design : Prospect i ve r and omized study of postoperative hemodynamically stable pediatric cardiac patients . The patients were given furosemide according to the urine output , either as an intermittent bolus injection or as a continuous infusion . Setting : Pediatric intensive care unit in a university hospital Patients : The patients were r and omly assigned before admission to either the intermittent i. v. or the continuous furosemide i. v. infusion group . Measurements and results : Demographic and hemodynamic data were recorded for a maximum of 72 h , as were furosemide dose , urine output , and fluid and inotropic drug requirements . Forty-six patients completed the study . Maximal hourly urine output was significantly higher in the intermittent group . A significantly lower dose of furosemide in the intermittent group produced the same 24-h urine volume as in the continuous infusion group . Conclusions : Intermittent furosemide administration may be recommended in hemodynamically stable postoperative pediatric cardiac patients because of less drug requirement . However , the high maximal urine output may cause hemodynamic problems in patients who depend on high inotropic support BACKGROUND Use of intravenous furosemide is generally avoided in critically ill neonates and infants soon after open heart operations to prevent fluctuations in intravascular volume and result ing circulatory instability . METHODS To assess and compare the safety and efficacy of continuous versus intermittent intravenous furosemide , we undertook a prospect i ve , r and omized trial in 26 consecutive patients less than 6 months of age . Inclusion criteria were presence of low-output syndrome requiring inotropic support ( 24/26 patients ) or pulmonary hypertension requiring vasodilator therapy ( 10/26 patients ) within 6 hours of discontinuation of cardiopulmonary bypass . Eleven patients received 0.1 mg x kg(-1 ) x h(-1 ) continuous intravenous furosemide ( group 1 ) and 15 received 1 mg/kg bolus every 4 hours ( group 2 ) for 24 hours . Mean age ( 3.7 + /- 3.4 versus 1.8 + /- 2.5 months ) and weight ( 4.6 + /- 2.1 versus 4.3 + /- 1.7 kg ) were comparable . RESULTS Group 2 infants showed slightly greater absolute urinary output ( 2.5 + /- 1.1 mL/kg per hour versus 3.3 + /- 1.1 mL/kg per hour , p = 0.05 ) . However , urinary output per dose of drug was significantly larger in group 1 infants ( 1.0 + /- 0.4 versus 0.5 + /- 0.2 mL x kg(-1 ) x h(-1 ) ; p = 0.002 ) with lesser fluctuations ( variance , 1.9 + /- 1.6 versus 3.8 + /- 2.1 ; p = 0.02 ) and fluid replacement needs ( 20.6 + /- 3.8 versus 51.8 + /- 14.4 ; p = 0.001 ) . Electrolyte replacement requirements were similar . A trend toward greater hemodynamic instability in group 2 patients ( heart rate variance 88.4 + /- 79.8 versus 128.3 + /- 82.7 ; p = 0.09 ; central venous pressure variance 2.8 + /- 1.90 versus 4.1 + /- 3.7 ; p = 0.07 ; mixed venous oxygen saturation variance , 32.3 + /- 27.6 versus 45.7 + /- 20.4 ; p = 0.06 ) was noted . All patients who completed the study protocol survived operation and were discharged home . CONCLUSIONS We conclude that ( 1 ) commonly used doses of both intermittent and continuous intravenous furosemide infusion can be safely administered to critically ill neonates and infants as early as 6 hours after operation , ( 2 ) continuous infusion yields an almost comparable urinary output with a much lower dose of furosemide , and ( 3 ) intermittent administration is associated with greater fluctuations in urinary output and greater needs for fluid replacement therapy BACKGROUND Routine diuretic administration after cardiopulmonary bypass is common despite the lack of evidence for its benefit . We performed a prospect i ve study to evaluate if diuretics assist in weight loss or alter clinical outcome . METHODS Seventy-nine patients undergoing primary elective coronary bypass surgery were r and omized to either diuretic ( fusemide and amiloride ) or placebo ( lactose ) postoperatively until preoperative weight was achieved or for 5 days in total . Proportions were compared with chi2 or Fisher 's exact test . RESULTS Forty patients were r and omized to diuretics and 39 to placebo . By day 5 , 97 % of patients ( 37 of 38 ) still in the diuretic arm , and 74 % of patients ( 29 of 39 ) in the placebo arm , achieved preoperative weight ( p = 0.02 ) . There were no differences in clinical outcomes . CONCLUSIONS Routine diuretics promote an earlier diuresis but no clinical benefits are apparent in low risk patients with normal renal function . Clinicians should reconsider routine diuretic prescription in this setting We prospect ively evaluated the diuretic effect of furosemide administered by bolus injection and by continuous infusion in 18 cardiac surgery patients . Nine patients were r and omly assigned to receive 0.3 mg/kg of furosemide as a bolus injection at time 0 and again 6 hours later ( nine patients ) or 0.05 mg/kg per hour of furosemide as a constant infusion for 12 hours ( nine patients ) . There were no significant differences between groups with respect to age , weight , creatinine clearance , changes in serum sodium and potassium levels , total urinary concentrations of sodium and potassium , or total urine volume for 12 hours . Diuresis during continuous infusion of furosemide was less variable from hour to hour than after bolus injection of furosemide and was sustained throughout the infusion period . Although the continuous infusion of furosemide will not provide the rapid and vigorous diuresis that is necessary in some clinical situations , it may be useful whenever a gentle , sustained diuresis is desired BACKGROUND Acute renal failure occurring in the postoperative period , requiring dialysis after cardiac surgery is an important risk factor for an early mortality , and the overall mortality of this complication is as high as 40 % to 60 % . Dialysis in the early postoperative period is often complicated by acute hemodynamic , metabolic , and hematologic effects that adversely affect cardiopulmonary function in patients stabilizing from recent surgery . The purpose of this study was to avoid the need for dialysis by infusion of the solution of mannitol , furosemide , and dopamine in the early postoperative period in oliguric renal failure . METHODS One hundred patients with postoperative oliguric or anuric renal failure despite adequate postoperative cardiac output and hemodynamic function were r and omized . Forty patients ( group A ) were given intermittent doses of diuretics ( furosemide , bumetadine , and ethracrynic acid ) and fluids . Sixty patients ( group B ) were given continuous infusion of the solution of mannitol , furosemide , and dopamine ; the infusion was started within 6 hours ( mean 3.5 hours ) in subgroup B1 ( n = 30 ) , and later than 6 hours ( mean 7.5 hours ) in subgroup B2 ( n = 30 ) after the onset of renal failure . RESULTS Diuresis occurred in 93.3 % of group B ( n = 56 ) versus 10 % in group A ( n = 4 ; patients with preop normal renal function ) . Ninety percent of group A ( n = 36 ) required dialysis versus only 6.7 % of group B ( n = 4 ; patients with preexisting renal disease of subgroup B2 ) . Renal function returned to preoperative normal ( serum creatinine 0.9 + /- 0.05 , p < 0.0001 ) or baseline value ( serum creatinine 2.5 + /- 0.01 , p < 0.0001 ) after first postoperative week in subgroup B1 and third postoperative week in subgroup B2 . CONCLUSIONS Infusion of solution of mannitol , furosemide , and dopamine promoted diuresis in patients with acute postoperative renal failure with adequate postoperative cardiac output and had decreased the need for dialysis in the majority of patients . Early administration of this solution in acute renal failure caused early restoration of renal function to normal or baseline status . It remains to be determined whether routine administration of this solution in the early postoperative period for oliguric renal failure influences the long-term mortality and morbidity in those patients who do require dialysis Because development of acute renal failure is one of the most potent predictors of outcome in cardiac surgery patients , the prevention of renal dysfunction is of utmost importance in perioperative care . In a double-blind r and omized controlled trial , the effectiveness of dopamine or furosemide in prevention of renal impairment after cardiac surgery was evaluated . A total of 126 patients with preoperatively normal renal function undergoing elective cardiac surgery received a continuous infusion of either " renal-dose " dopamine ( 2 microg/kg per min ) ( group D ) , furosemide ( 0.5 microg/kg per min ) ( group F ) , or isotonic sodium chloride as placebo ( group P ) , starting at the beginning of surgery and continuing for 48 h or until discharge from the intensive care unit , whichever came first . Renal function parameters and the maximal increase of serum creatinine above baseline value within 48 h ( deltaCrea(max ) ) were determined . The increase in plasma creatinine was twice as high in group F as in groups D and P ( P < 0.01 ) . Acute renal injury ( defined as deltaCreamax ) > 0.5 mg/dl ) occurred more frequently in group F ( six of 41 patients ) than in group D ( one of 42 ) and group P ( zero of 40 ) ( P < 0.01 ) . ( The difference between group D and group P was not significant . ) Creatinine clearance was lower in group F ( P < 0.05 ) . Two patients in group F required renal replacement therapy . The mean volume of infused fluids , blood urea nitrogen , serum sodium , serum potassium , and osmolar- and free-water clearance was similar in all groups . It was shown that continuous infusion of dopamine for renal protection was ineffective and was not superior to placebo in preventing postoperative dysfunction after cardiac surgery . In contrast , continuous infusion of furosemide was associated with the highest rate of renal impairment . Thus , renaldose dopamine is ineffective and furosemide is even detrimental in the protection of renal dysfunction after cardiac surgery OBJECTIVE Acute kidney injury ( AKI ) is a devastating complication following cardiac surgery and the ideal management is controversial . This prospect i ve , r and omized , open-label and double-blinded study analyzed the renoprotective effects of furosemide infusion and intermittent bolus therapy administered with dopamine infusion in cardiac surgical patients . METHODS Between August 1 , 2007 and July 31 , 2008 , 100 adult patients undergoing elective coronary artery bypass surgery ( CABG ) surgery with normal renal function ( creatinine < 1.4 mg/dl ) were enrolled in the study . The patients were r and omized for the comparison of intermittent ( Group 1 , n=50 , 1mg-3mg/kg ) and continuous infusion of furosemide ( Group 2 , n=50 , 10mg/ml ) . Continuous variables were expressed as mean+/- SD and compared by unpaired Student 's t test or ANOVA for repeated measures . Statistical significance was assumed if p value was < 0.05 . RESULTS Renal replacement therapy ( RRT ) was used in 5 % of patients ( all in group 1 , p=0.028 ) . The 30-day mortality was 5 % . Only 2 patients became hemodialysis dependent in group 1 . Group 2 patients showed a continuous and higher urine output postoperatively than group 1 ( p<0.001 ) . Both groups had significant increase in peak postoperative serum creatinine values ( p<0.001 ) , however peak postoperative creatinine-clearance was significantly lower in group 1 ( p<0.001 ) . CONCLUSION Acute kidney injury necessitating RRT makes a small percentage of patients undergoing cardiac surgery and if RRT is not required the survival is excellent . Continuous infusion of furosemide seems to be effective in promoting diuresis and decreasing the need for RRT . However further multicenter studies with different doses of furosemide are required to confirm these results OBJECTIVE Renal dysfunction following cardiac surgery is more apparent in high-risk patients with pre-existing renal dysfunction , diabetes and impaired left-ventricular function , and following complicated procedures involving prolonged cardiopulmonary bypass ( CPB ) . The aim of this prospect ively r and omised double-blinded placebo-controlled study was to evaluate reno-protective effect of low-dose furosemide infusion in this high-risk group . METHODS Patients with preoperative serum creatinine > 130 micromol/l ( 1.4 mg/dl ) , left-ventricular ejection fraction < 50 % , congestive heart failure , diabetes , or procedures involving prolonged CPB were r and omised to receive either saline at 2 ml/h ( n=21 ) , or furosemide at 4 mg/h ( n=21 ) . Infusion was commenced after induction of anaesthesia and continued for 12h postoperatively . Renal dysfunction was defined as > 50 % increase in serum creatinine postoperatively , or > 130 micromol/l ( 1.4 mg/dl ) , or requirement for haemodialysis , or all of these . In patients with preoperative serum creatinine > 130 micromol/l , > 50 % increase over preoperative levels was used to define postoperative renal dysfunction . RESULTS Following cardiac surgery , patients receiving furosemide had a higher urine output ( 3.4+/-1.2 ml/kg/h in furosemide group and 1.2+/-0.5 ml/kg/h in placebo group ; p<0.001 ) , higher postoperative fluid requirement ( 4631+/-1359 ml in furosemide group and 3714+/-807 ml in placebo group , p=0.011 ) , and lower urinary-creatinine ( 2+/-1.3 micromol/l in furosemide group and 5.9+/-2.5 micromol/l in placebo group p<0.001 ) . Both groups had significant increase in retinol binding protein/creatinine ratio ( 7.2+/-6 to 3152+/-1411 in furosemide group ; 4.9+/-2.1 to 2809+/-1125 in placebo group ; p<0.001 ) and peak serum creatinine ( 98+/-33 to 177+/-123 micromol/l in furosemide group ; 96+/-20 to 143+/-87 micromol/l in placebo group ; p<0.001 ) , and a significant decrease in peak creatinine-clearance ( 64.3+/-29.4 to 39.1+/-16.6 ml/min in furosemide group ; 65.5+/-38.6 to 41.8+/-17.8 ml/min in placebo group ; p<0.001 ) following cardiac surgery , implying significant renal injury following cardiac surgery . Peak creatinine levels ( 177+/-123 micromol/l in furosemide group and 143+/-87 micromol/l in placebo group ; p=0.35 ) and peak creatinine-clearance ( 39.1+/-16.6 ml/min in furosemide group and 41.8+/-17.8 ml/min in placebo group ; p=0.61 ) were similar in the two groups . Importantly , there was no difference in incidence of renal dysfunction between the furosemide group ( 9/21 ) and the control group ( 8/21 ) ( relative risk 1.1 , 95 % confidence interval 0.6 - 2.2 ; p=0.99 ) . CONCLUSIONS Our r and omised trial did not demonstrate any benefit of furosemide-infusion postoperatively in high-risk cardiac surgical patients . Although urinary output increased with furosemide , there was no decrease in renal injury , and no decrease in incidence of renal dysfunction |
10,351 | 28,295,308 | No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC .
However , afatinib was more effective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma .
The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib | Gefitinib , erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR TKIs ) for treating advanced non-small cell lung cancer ( NSCLC ) with proven efficacy .
We undertook a systematic review and meta- analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety . | Purpose : Somatic mutations in the epidermal growth factor receptor ( EGFR ) have been detected in patients with non – small cell lung cancer ( NSCLC ) and are associated with sensitivity to treatment with gefitinib or erlotinib . Our study explored the relationship between the two most common types of somatic EGFR mutations , exon 19 deletions and the L858R point mutation , and outcomes of patients following treatment with gefitinib or erlotinib . Experimental Design : Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations . Patients with exon 19 deletion or L858R mutations were identified . The response rate , time to progression , and overall survival were determined for the two groups . Results : We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib . Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation ( 38 versus 17 months ; P = 0.04 ) . There were also trends toward higher response rate ( 73 % versus 50 % ) and improved time to progression ( 24 versus 10 months ) for the patients with an exon 19 deletion , although these were not independently significant in a multivariate analysis . A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [ 18 of 23 ( 78 % ) versus 3 of 9 ( 33 % ) ; P = 0.04 ] . No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients . Conclusions : Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation . Pooling of greater numbers of patients and completion of prospect i ve trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib , erlotinib , and other EGFR inhibitors Background In Non-small cell lung cancer ( NSCLC ) , an overactive epidermal growth factor receptor ( EGFR ) pathway is a component of the malignant phenotype . Two tyrosine kinase inhibitors ( TKIs ) of EGFR , gefinitib and erlotinib , have been used with variable benefit . Methods We have analyzed outcome data of a population of NSCLC patients that received these TKIs to determine the benefit derived and to define the clinical and molecular parameters that correlate with response . Tumor tissue from a subgroup of these patients was analyzed by immunohistochemistry to measure the expression level of EGFR and four activated ( phosphorylated ) members of the pathway , pEGFR , pERK , pAKT , and pSTAT3 . Results Erlotinib was slightly superior to gefitinib in all measures of response , although the differences were not statistically significant . The most robust clinical predictors of time to progression ( TTP ) were best response and rash ( p < 0.0001 ) . A higher level of pEGFR was associated with longer TTP , while the total EGFR level was not associated with response . Higher levels of pAKT and pSTAT3 were also associated with longer TTP . In contrast , a higher level of pERK1/2 was associated with shorter TTP . Conclusion These observations suggest the hypothesis that tumor cells that have activated EGFR pathways , presumably being utilized for survival , are clinical ly relevant targets for pathway inhibition . An accurate molecular predictive model of TKI response should include activated members of the EGFR pathway . TKIs may be best reserved for tumors expressing pEGFR and pAKT or pSTAT , and little pERK . In the absence of molecular predictors of response , the appearance of a rash and a positive first scan are good clinical indicators of response BACKGROUND The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib are approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer ( NSCLC ) . We aim ed to compare the efficacy and safety of afatinib and gefitinib in this setting . METHODS This multicentre , international , open-label , exploratory , r and omised controlled phase 2B trial ( LUX-Lung 7 ) was done at 64 centres in 13 countries . Treatment-naive patients with stage IIIB or IV NSCLC and a common EGFR mutation ( exon 19 deletion or Leu858Arg ) were r and omly assigned ( 1:1 ) to receive afatinib ( 40 mg per day ) or gefitinib ( 250 mg per day ) until disease progression , or beyond if deemed beneficial by the investigator . R and omisation , stratified by EGFR mutation type and status of brain metastases , was done central ly using a vali date d number generating system implemented via an interactive voice or web-based response system with a block size of four . Clinicians and patients were not masked to treatment allocation ; independent review of tumour response was done in a blinded manner . Co primary endpoints were progression-free survival by independent central review , time-to-treatment failure , and overall survival . Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug . This ongoing study is registered with Clinical Trials.gov , number NCT01466660 . FINDINGS Between Dec 13 , 2011 , and Aug 8 , 2013 , 319 patients were r and omly assigned ( 160 to afatinib and 159 to gefitinib ) . Median follow-up was 27·3 months ( IQR 15·3 - 33·9 ) . Progression-free survival ( median 11·0 months [ 95 % CI 10·6 - 12·9 ] with afatinib vs 10·9 months [ 9·1 - 11·5 ] with gefitinib ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·57 - 0·95 ] , p=0·017 ) and time-to-treatment failure ( median 13·7 months [ 95 % CI 11·9 - 15·0 ] with afatinib vs 11·5 months [ 10·1 - 13·1 ] with gefitinib ; HR 0·73 [ 95 % CI 0·58 - 0·92 ] , p=0·0073 ) were significantly longer with afatinib than with gefitinib . Overall survival data are not mature . The most common treatment-related grade 3 or 4 adverse events were diarrhoea ( 20 [ 13 % ] of 160 patients given afatinib vs two [ 1 % ] of 159 given gefitinib ) and rash or acne ( 15 [ 9 % ] patients given afatinib vs five [ 3 % ] of those given gefitinib ) and liver enzyme elevations ( no patients given afatinib vs 14 [ 9 % ] of those given gefitinib ) . Serious treatment-related adverse events occurred in 17 ( 11 % ) patients in the afatinib group and seven ( 4 % ) in the gefitinib group . Ten ( 6 % ) patients in each group discontinued treatment due to drug-related adverse events . 15 ( 9 % ) fatal adverse events occurred in the afatinib group and ten ( 6 % ) in the gefitinib group . All but one of these deaths were considered unrelated to treatment ; one patient in the gefitinib group died from drug-related hepatic and renal failure . INTERPRETATION Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib , with a manageable tolerability profile . These data are potentially important for clinical decision making in this patient population . FUNDING Boehringer Ingelheim PURPOSE The epidermal growth factor receptor ( EGFR ) tyrosine kinase has been an important target for non-small-cell lung cancer . Several EGFR tyrosine kinase inhibitors ( TKIs ) are currently approved , and both gefitinib and erlotinib are the most well-known first-generation EGFR-TKIs . This r and omized phase III study was conducted to investigate the difference between these two EGFR-TKIs . PATIENTS AND METHODS Previously treated patients with lung adenocarcinoma were r and omly assigned to receive gefitinib or erlotinib . This study aim ed to investigate the noninferiority of gefitinib compared with erlotinib . The primary end point was progression-free survival ( PFS ) . RESULTS Five hundred sixty-one patients were r and omly assigned , including 401 patients ( 71.7 % ) with EGFR mutation . All baseline factors ( except performance status ) were balanced between the arms . Median PFS and overall survival times for gefitinib and erlotinib were 6.5 and 7.5 months ( hazard ratio [ HR ] , 1.125 ; 95 % CI , 0.940 to 1.347 ; P = .257 ) and 22.8 and 24.5 months ( HR , 1.038 ; 95 % CI , 0.833 to 1.294 ; P = .768 ) , respectively . The response rates for gefitinib and erlotinib were 45.9 % and 44.1 % , respectively . Median PFS times in EGFR mutation-positive patients receiving gefitinib versus erlotinib were 8.3 and 10.0 months , respectively ( HR , 1.093 ; 95 % CI , 0.879 to 1.358 ; P = .424 ) . The primary grade 3 or 4 toxicities were rash ( 2.2 % for gefitinib v 18.1 % for erlotinib ) and alanine aminotransferase (ALT)/aspartate aminotransferase ( AST ) elevation ( 6.1%/13.0 % for gefitinib v 2.2%/3.3 % for erlotinib ) . CONCLUSION The study did not demonstrate noninferiority of gefitinib compared with erlotinib in terms of PFS in patients with lung adenocarcinoma according to the predefined criteria BACKGROUND AND OBJECTIVE It has been proven that epidermal growth factor receptor-tyrosine kinase inhibitor ( EGFR-TKI ) significantly benefits advanced non-small cell lung cancer ( NSCLC ) patients harboring EGFR mutations in progression-free survival time with better tolerance . This study is undertaken to analyze efficacy and tolerance of advanced NSCLC patients harboring EGFR mutations taking EGFR-TKI as a first-line therapy . METHODS Tumor sample s from 54 patients with advanced NSCLC were examined for EGFR activating mutations ( deletion mutation in exon 19 and the L858R point mutation in exon 21 ) by direct sequencing . The patients were first-line treated with oral administration of EGFR-TKI until disease progression . The efficacy and adverse events were observed , and survival was followed up . RESULTS Among the patients , 61 % ( 33 of 54 ) had EGFR exon 19 deletion , and 39 % ( 21 of 54 ) had EGFR L858R point mutation . All patients received first-line TKI therapy . The total response rate was 96 % , median progression free survival ( PFS ) was 8.3 months and median survival was 19.5 months . The patients with EGFR exon 19 deletion had significantly longer median PFS ( 9 versus 7 months , P=0.002 ) and longer median overall survival (OS)(25 versus 16 months , P=0.001 ) than patients with EGFR L858R point mutation . There is no significance in efficacy between gefitinib and erlotinib , and gefitinib is safer than erlotinib . The most common adverse events were rash and diarrhea . Two ( 4 % ) grade 4 skin toxity effects , two ( 4 % ) grade 3 aminotransferase level elevations , and one ( 1 ) grade 3 stomatitis were observed . CONCLUSION The first-line EGFR-TKI treatment in advanced NSCLC patients harboring EGFR mutations is efficient and safe , which is more efficient in patients with EGFR exon 19 deletion than those with EGFR L858R mutation 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 PURPOSE To establish the safety and tolerability of ZD1839 ( Iressa ) , a selective epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types . PATIENTS AND METHODS This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days . Patients with either advanced non-small-cell lung , ovarian , head and neck , prostate , or colorectal cancer were recruited . RESULTS Eighty-eight patients received ZD1839 ( 150 to 1,000 mg/d ) . At 1,000 mg/d , five of 12 patients experienced dose-limiting toxicity ( grade 3 diarrhea [ four patients ] and grade 3 somnolence [ one patient ] ) . The most frequent drug-related adverse events ( AEs ) were acne-like rash ( 64 % ) and diarrhea ( 47 % ) , which were generally mild ( grade 1/2 ) and reversible on cessation of treatment . No change in ZD1839 safety profile was observed with prolonged administration . Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98 % of patients by day 7 . Nineteen patients had stable disease and received ZD1839 for > or= 3 months ; seven of these patients remained on study drug for > or= 6 months . Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway . CONCLUSION ZD1839 was generally well tolerated , with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d . ZD1839 treatment result ed in clinical ly meaningful disease stabilization across a range of tumor types and doses . Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling , which was predicted from the mode of action of ZD1839 Background / Aims The efficacy and safety of pemetrexed , gefitinib , and erlotinib administration in previously treated patients with non-small cell lung cancer ( NSCLC ) were compared . Methods The study patients met the following criteria : histologically confirmed , previously treated advanced ( stage IIIB or IV ) or recurrent NSCLC ; a measurable lesion ; ≥ 18 years of age ; Eastern Cooperative Oncology Group Performance status 0 to 2 ; and no prior exposure to the three study drugs . Patients received 500 mg/m2 of pemetrexed intravenously every 3 weeks with vitamin supplementation , gefitinib ( 250 mg/day per os ) , or erlotinib ( 150 mg/day per os ) . Results Of 57 patients ( pemetrexed , 20 ; gefitinib , 20 ; and erlotinib , 17 ) , 55 were evaluated for a response . The numbers of males , smokers , and squamous histology were increased in the pemetrexed group compared to the other groups . The objective response rates were 5.3 % , 25.0 % , and 12.5 % ( p = 0.22 ) , and the disease control rates ( DCR ) were 5.3 % , 40.0 % , and 50.0 % , respectively ( p < 0.01 ) . The median progression-free survival ( PFS ) was 1.7 , 3.5 , and 4.4 months ( p < 0.01 ) and the median overall survival ( OS ) was 5.6 , 21.8 , and 21.5 months ( p = 0.04 ) , respectively . In subgroup analyses , patients with non-squamous histology , males , and a smoking history had a higher DCR and longer PFS with gefitinib and erlotinib than with pemetrexed . All three chemotherapeutic agents had manageable toxicities . Conclusions Both oral epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR TKIs ) had comparable efficacy and safety . The superior PFS and OS of EGFR TKIs with more favorable baseline clinical characteristics than those of pemetrexed suggest the impact of baseline clinicopathological factors Several r and omized trials have demonstrated non-small cell lung cancer ( NSCLC ) patients with activating epidermal growth factor receptor ( EGFR ) mutations can achieve favorable clinical outcomes on treatment with EGFR tyrosine kinase inhibitors ( TKIs ) . EGFR mutation is considered as a predictive marker for efficacy of EGFR-TKIs in NSCLC . Here we show miR-200c overexpression was correlated with the epithelial phenotype and sensitivity to gefitinib in EGFR wild-type NSCLC cell lines . Up-regulated miR-200c could regain the sensitivity to gefitinib in the EGFR wild-type cell lines and miR-200c could regulate epithelial to mesenchymal transition through PI3K/AKT and MEK/ERK pathways . NSCLC patients at advanced stage ( N=150 ) who received EGFR-TKIs ( gefitinib or erlotinib ) as second- or third-line therapy from September 2008 to December 2012 were included in the study . In 66 NSCLC patients with wild-type EGFR , high levels of miR-200c expression was associated with higher disease control rate ( DCR ) , longer progression-free survival ( PFS ) and longer overall survival ( OS ) compared with low miR-200c expression subgroup . In the subgroup with EGFR mutation , the trend remained the same but not statistically significant . Overall , these findings indicated that miR-200c might be a predictive biomarker for sensitivity to EGFR-TKIs in advanced NSCLC patients with wild-type EGFR Background The objective of the study was to observe the efficacy and safety of pulsatile administration of high‐dose gefitinib or erlotinib in patients with advanced non‐small cell lung cancer ( NSCLC ) with secondary drug resistance to st and ard doses of tyrosine kinase inhibitor ( TKI ) treatment . Material s and methods We recruited 42 NSCLC patients from our hospital , between August 2014 and December 2015 , who had experienced drug resistance after one year of conventional treatment with gefitinib or erlotinib . The gefitinib group ( 29 patients ) received one dose of 1000 mg gefitinib every four days . The erlotinib group ( 13 patients ) received one dose of 450 mg erlotinib every three days . Treatments continued until disease progression according to Response Evaluation Criteria In Solid Tumors 1.1 or development of intolerable toxicity . Results Median progression‐free survival ( PFS ) was 30 months ( gefitinib vs. erlotinib : 31 vs. 24 months ; P > 0.05 ) . After high‐dose pulsatile administration , eight patients achieved a partial response ( PR ) , 11 had stable disease ( SD ) , and 23 had progressive disease ( PD ; relative risk 19.0 % ; disease control rate 45.2 % ; median PFS six months ) . Patients were categorized based on epidermal growth factor receptor gene mutation : exon 19 ( no patients achieved complete response [ CR ] , 4 PR , 6 SD , and 17 PD ) and exon 21 mutation groups ( no patients achieved CR , 4 PR , 5 SD , and 6 PD ) . Conclusion High‐dose TKI pulsatile treatment is safe , efficient , and can improve prognoses for certain patients with advanced NSCLC OBJECTIVE To compare the effectiveness and cost-effectiveness of erlotinib versus gefitinib as first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients . DESIGN . Indirect treatment comparison and a cost-effectiveness assessment . SETTING Hong Kong . PATIENTS Those having epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer . INTERVENTIONS Erlotinib versus gefitinib use was compared on the basis of four relevant Asian phase-III r and omised controlled trials : one for erlotinib ( OPTIMAL ) and three for gefitinib ( IPASS ; NEJGSG ; WJTOG ) . The cost-effectiveness assessment model simulates the transition between the health states : progression-free survival , progression , and death over a lifetime horizon . The World Health Organization criterion ( incremental cost-effectiveness ratio <3 times of gross domestic product/capita : < US$ 102 582 ; approximately < HK$798 078 ) was used to rate cost-effectiveness . RESULTS The best fit of study characteristics and prognostic patient characteristics were found between the OPTIMAL and IPASS trials . Comparing progression-free survival hazard ratios of erlotinib versus gefitinib using only these r and omised controlled trials in an indirect treatment comparison result ed in a statistically significant progression-free survival difference in favour of erlotinib ( indirect treatment comparison hazard ratio=0.33 ; 95 % confidence interval , 0.19 - 0.58 ; P=0.0001 ) . The cost-effectiveness assessment model showed that the cost per progression-free life year gained and per quality -adjusted life year gained was at acceptable values of US$ 39 431 ( approximately HK$306 773 ) and US$ 62 419 ( approximately HK$485 619 ) for erlotinib versus gefitinib , respectively . CONCLUSION The indirect treatment comparison of OPTIMAL versus IPASS shows that erlotinib is significantly more efficacious than gefitinib . Furthermore , the cost-effectiveness assessment indicates that the incremental cost-effectiveness ratios are well within an acceptable range in relation to the survival benefits obtained . In conclusion , erlotinib is cost-effective compared to gefitinib for first-line epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors ( TKIs ) have been shown to improve the prognosis of EGFR-mutated ( exon 19/21 ) non-small cell lung carcinoma ( NSCLC ) . Positive EGFR mutation status is associated with NSCLC in non-smokers . Genetic and environmental factors have been linked to the etiology of EGFR mutations and sensitivity to EGFR-TKIs in non-smoking NSCLC patients . Cooking fume exposure ( CFE ) has also been proposed as an etiologic factor for NSCLC in non-smokers ; however , the association of CFE with EGFR mutation status and EGFR-TKI response is unclear . The objective of this study was to determine the association between CFE and clinical response to EGFR-TKI therapy in NSCLC . The association of CFE , smoking history , occupational hazard exposure , tumor pathological type , EGFR mutation status , environmental exposure , living environment , and performance status with EGFR-TKI efficacy was determined in metastatic NSCLC patients who were treated with EGFR-TKIs ( gefitinib or erlotinib ) . Objective response rate ( ORR ) and progression-free survival ( PFS ) were used to evaluate EGFR-TKI response . A total of 273 patients with a median age of 60.97 years ( range 27–86 years ) were included in this study . The proportion of patients receiving gefitinib and erlotinib was 72.53 % ( 198/273 ) and 27.47 % ( 75/273 ) , respectively . ORRs ( complete + partial responses ) to gefitinib and erlotinib treatment were 20.70 % ( 41/198 ) and 14.67 % ( 11/75 ) , respectively . Of the 273 patients , 98 ( 36.03 % ) had CFE and 112 ( 44.69 % ) had exposed to tobacco smoke . EGFR mutations were present in 55 patients , including exon 19 deletion ( n = 43 ) and exon 21 point mutations ( n = 12 ) . Of the 55 EGFR mutation-positive patients , 52 ( 94.5 % ) had CFE . In the multivariate conditional logistic analysis , clinical response to EGFR-TKI was associated with non-smoking status , EGFR mutation , and CFE . Among these factors , CFE was the strongest predictor of EGFR-TKI response ( odds ratio 13.66 ; 95 % confidence interval ( CI ) 5.66–32.98 ; P < 0.001 ) . PFS was associated with a performance status of 0/1 , adenocarcinoma pathological type , non-smoking status , EGFR mutation , and CFE . Among these , CFE was the most important factor for longer PFS ( hazard ratio 0.37 ; 95 % CI 0.26–0.52 ; P < 0.001 ) . The median PFS was 15.15 months in patients with CFE and 4.37 months in those without ( P < 0.0001 ) . Knowledge of CFE history might be useful as a response predictor to EGFR-TKI treatment in NSCLC . Furthermore , CFE history might help to assess EGFR mutation status when genetic testing is not available PURPOSE Gefitinib and erlotinib are potent EGFR TKIs , with antitumor activity . In this r and omized , single-center , non-comparative phase II trial , the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with locally advanced , metastatic stage IIIB/IV NSCLC who failed first-line chemotherapy and had either EGFR mutation or at least two out of three clinical factors associated with higher incidence of EGFR mutations ( female , adenocarcinoma histology , and never-smoker ) were eligible . RESULTS A total of 96 ( 48 per arm ) patients were r and omly assigned to gefitinib- or erlotinib-arm , respectively . Baseline characteristics were well-balanced between the two arms . The response rates ( RR ) were 47.9 % in the gefitinib arm and 39.6 % in the erlotinib arm . Median PFS was 4.9 months ( 95 % CI , 1.3 - 8.5 ) in the gefitinib arm and 3.1 months ( 95 % CI , 0.0 - 6.4 ) in the erlotinib arm . The most common grade 3/4 toxicity was skin rash . Exploratory analyses showed that there was no significant difference in RR and PFS in the gefitinib arm compared to the erlotinib arm ( RR ( % ) 47.9 vs. 39.6 , p=0.269 ; median survival ( months ) 4.9 vs. 3.1 , p=0.336 ) . There was no significant difference in QOL between the two arms . CONCLUSION Both gefitinib and erlotinib showed effective activity and tolerable toxicity profiles as second-line treatment for the selected population of NSCLC . We may consider conducting a phase III trial to directly compare the efficacy and toxicity between gefitinib and erlotinib in an enriched patient population Introduction : Although st and ard schedule of gefitinib was the administration of 250 mg tablet every day , many patients need dose reduction because of toxicities . However , the efficacy of such low-dose gefitinib for patients with epidermal growth factor receptor-mutated non-small cell lung cancer has rarely been evaluated . Methods : A post hoc comparison of the efficacy ( response rate and survival ) in patients treated with gefitinib with or without any dose reduction in NEJ002 study was performed . Results : Among 114 patients treated with first-line gefitinib in NEJ002 , 61 ( 54 % ) continued gefitinib without any dose reduction until their diseases progressed , and 53 ( 46 % ) reduced their dose of gefitinib because of some toxicities . There was no significant difference of patient characteristics between the two groups . The progression-free survival of low-dose group tended to be better than that of st and ard-dose group ( median progression-free survival , 11.8 versus 9.9 months ; p = 0.144 ) , and the overall survival of low-dose group was also better than that of st and ard-dose group ( median survival time , 32.7 versus 25.3 months ; p = 0.049 ) . Conclusions : The results suggest that low-dose gefitinib may be clinical ly not inferior to st and ard-dose gefitinib for non-small cell lung cancer with sensitive epidermal growth factor receptor mutations . Prospect i ve study of low-dose gefitinib is warranted especially for frail patients who need less toxic treatment PURPOSE To assess the feasibility of administering OSI-774 , to recommend a dose on a protracted , continuous daily schedule , to characterize its pharmacokinetic behavior , and to acquire preliminary evidence of anticancer activity . PATIENTS AND METHODS Patients with advanced solid malignancies were treated with escalating doses of OSI-774 in three study parts ( A to C ) to evaluate progressively longer treatment intervals . Part A patients received OSI-774 25 to 100 mg once daily , for 3 days each week , for 3 weeks every 4 weeks . Part B patients received OSI-774 doses ranging from 50 to 200 mg given once daily for 3 weeks every 4 weeks to establish the maximum tolerated dose ( MTD ) . In part C , patients received this MTD on a continuous , uninterrupted schedule . The pharmacokinetics of OSI-774 and its O-demethylated metabolite , OSI-420 , were characterized . RESULTS Forty patients received a total of 123 28-day courses of OSI-774 . No severe toxicities precluded dose escalation of OSI-774 from 25 to 100 mg/d in part A. In part B , the incidence of severe diarrhea and /or cutaneous toxicity was unacceptably high at OSI-774 doses exceeding 150 mg/d . Uninterrupted , daily administration of OSI-774 150 mg/d represented the MTD on a protracted daily schedule . The pharmacokinetics of OSI-774 were dose independent ; repetitive daily treatment did not result in drug accumulation ( at 150 mg/d [ average ] : minimum steady-state plasma concentration , 1.20 + /- 0.62 microg/mL ; clearance rate , 6.33 + /- 6.41 L/h ; elimination half-life , 24.4 + /- 14.6 hours ; volume of distribution , 136 . 4 + /- 93.1 L ; area under the plasma concentration-time curve for OSI-420 relative to OSI-774 , 0.12 + /- 0.12 microg/h/mL ) . CONCLUSION The recommended dose for disease-directed studies of OSI-774 administered orally on a daily , continuous , uninterrupted schedule is 150 mg/d . OSI-774 was well tolerated , and several patients with epidermoid malignancies demonstrated either antitumor activity or relatively long periods of stable disease . The precise contribution of OSI-774 to these effects is not known The objective of this study was to evaluate the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR-TKIs ) in patients undergoing dose reduction and in those with a low body surface area ( BSA ) . The association between dose reduction , low BSA and efficacy , including response rate ( RR ) , disease control rate ( DCR ) , progression-free survival ( PFS ) and overall survival ( OS ) , were evaluated in patients prescribed TKIs between September , 2002 and May , 2013 . A total of 282 patients received EGFR-TKIs during the study period , 53 ( 18.8 % ) of whom underwent a dose reduction ( 21.4 and 31.6 % of the patients with a BSA of < 1.5 and < 1.25 m2 , respectively ) . Eleven ( 20.8 % ) of these 53 patients had a dose reduction due to adverse events ( AEs ) > grade 3 . In either gefitinib or erlotinib treatment , the RR , DCR , PFS and OS in EGFR-mutated patients with a BSA of < 1.5 m2 were not different from those in patients with a BSA of > 1.5 m2 . In addition , there were no differences in these parameters between patients with and those without a dose reduction of TKIs . The dose of TKIs in patients with AEs and in those with low BSA should be determined with caution . To confirm the equal efficacy of TKIs in patients undergoing a dose reduction , prospect i ve observational studies with less patient heterogeneity are required BACKGROUND There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung . LUX-Lung 8 compared afatinib ( an irreversible ErbB family blocker ) with erlotinib ( a reversible EGFR tyrosine kinase inhibitor ) , as second-line treatment for patients with advanced squamous cell carcinoma of the lung . METHODS We did this open-label , phase 3 r and omised controlled trial at 183 cancer centres in 23 countries worldwide . We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy . Participants were r and omly assigned ( 1:1 ) to receive afatinib ( 40 mg per day ) or erlotinib ( 150 mg per day ) until disease progression . The r and omisation was done central ly with an interactive voice or web-based response system and stratified by ethnic origin ( eastern Asian vs non-eastern Asian ) . Clinicians and patients were not masked to treatment allocation . The primary endpoint was progression-free survival assessed by independent central review ( intention-to-treat population ) . The key secondary endpoint was overall survival . This trial is registered with Clinical Trials.gov , NCT01523587 . FINDINGS 795 eligible patients were r and omly assigned ( 398 to afatinib , 397 to erlotinib ) . Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months ( IQR 3·1 - 10·2 ) , at which point enrolment was not complete . Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib ( median 2·4 months [ 95 % CI 1·9 - 2·9 ] vs 1·9 months [ 1·9 - 2·2 ] ; hazard ratio [ HR ] 0·82 [ 95 % CI 0·68 - 1·00 ] , p=0·0427 ) . At the time of the primary analysis of overall survival ( median follow-up 18·4 months [ IQR 13·8 - 22·4 ] ) , overall survival was significantly greater in the afatinib group than in the erloinib group ( median 7·9 months [ 95 % CI 7·2 - 8·7 ] vs 6·8 months [ 5·9 - 7·8 ] ; HR 0·81 [ 95 % CI 0·69 - 0·95 ] , p=0·0077 ) , as were progression-free survival ( median 2·6 months [ 95 % CI 2·0 - 2·9 ] vs 1·9 months [ 1·9 - 2·1 ] ; HR 0·81 [ 95 % CI 0·69 - 0·96 ] , p=0·0103 ) and disease control ( 201 [ 51 % ] of 398 patients vs 157 [ 40 % ] of 397 ; p=0·0020 ) . The proportion of patients with an objective response did not differ significantly between groups ( 22 [ 6 % ] vs 11 [ 3 % ] ; p=0·0551 ) . Tumour shrinkage occurred in 103 ( 26 % ) of 398 patients versus 90 ( 23 % ) of 397 patients . Adverse event profiles were similar in each group : 224 ( 57 % ) of 392 patients in the afatinib group versus 227 ( 57 % ) of 395 in the erlotinib group had grade 3 or higher adverse events . We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib ( 39 [ 10 % ] vs nine [ 2 % ] ) , of grade 3 stomatitis with afatinib ( 16 [ 4 % ] vs none ) , and of grade 3 rash or acne with erlotinib ( 23 [ 6 % ] vs 41 [ 10 % ] ) . INTERPRETATION The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib , along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung . FUNDING Boehringer Ingelheim Introduction : Leptomeningeal carcinomatosis ( LMC ) from non – small-cell lung cancer ( NSCLC ) is a clinical ly important neurological complication in the era of epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( TKIs ) . The purpose of this study was to compare the efficacy of gefitinib and erlotinib for control of LMC in NSCLC . Methods : We retrospectively review ed medical records of 25 EGFR TKI – treated NSCLC patients with LMC between 2004 and 2012 at Seoul National University Hospital . Cytologic negative conversion was defined as absence of malignant cells in the cerebrospinal fluid three times in succession . Cytologic conversion rates were compared between the gefitinib arm and the erlotinib arm . Results : Nine patients had exon 21 point mutations and eight patients had exon 19 deletional mutations . Nine of 25 patients had already used EGFR TKIs and switched to another EGFR TKI after LMC occurrence . The other 16 patients received EGFR TKIs after LMC diagnoses . All the patients received intrathecal chemotherapy , including methotrexate , and six of them were treated with combined whole-brain radiotherapy . Gefitinib and erlotinib were administered to 11 and 14 patients , respectively . Ten patients had LMC controlled with cytologic negative conversion , whereas in 15 patients , cytological clearance of the cerebrospinal fluid could not be achieved . Patients treated with erlotinib showed better cytologic conversion rate of LMC than those with gefitinib ( 64.3 % [ 9 of 14 ] in the erlotinib arm versus 9.1 % [ 1 of 11 ] in the gefitinib arm ; p = 0.012 ) . Conclusion : This study suggested that erlotinib had better control rate for LMC in NSCLC than gefitinib . Further prospect i ve study is warranted OBJECTIVE To compare the efficacy of the erlotinib versus gefitinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC . METHODS Fifty patients with untreated advanced EGFR mutation- positive NSCLC were r and omly divided into gefitinib group ( n=27 ) and erlotinib group ( n=23 ) . The progression-free survival , objective response rate and disease control rate were evaluated to compare the efficacy of gefitinib and erlotinib . RESULTS There were no significant differences in the objective response rate ( P=0.711 ) and disease control rate ( P=0.861 ) between the two groups . The progression-free survival of gefitinib group and erlotinib group was 8.0 months and 10.0 months , respectively . The efficacy of the two drugs was similar ( P=0.293 ) . CONCLUSION There is no significant differences between gefitinib and erlotinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC BACKGROUND This placebo-controlled phase III study investigated the effect on survival of gefitinib as second-line or third-line treatment for patients with locally advanced or metastatic non-small-cell lung cancer . METHODS 1692 patients who were refractory to or intolerant of their latest chemotherapy regimen were r and omly assigned in a ratio of two to one either gefitinib ( 250 mg/day ) or placebo , plus best supportive care . The primary endpoint was survival in the overall population of patients and those with adenocarcinoma . The primary analysis of the population for survival was by intention to treat . This study has been su bmi tted for registration with Clinical Trials.gov , number 1839IL/709 . FINDINGS 1129 patients were assigned gefitinib and 563 placebo . At median follow-up of 7.2 months , median survival did not differ significantly between the groups in the overall population ( 5.6 months for gefitinib and 5.1 months for placebo ; hazard ratio 0.89 [ 95 % CI 0.77 - 1.02 ] , p=0.087 ) or among the 812 patients with adenocarcinoma ( 6.3 months vs 5.4 months ; 0.84 [ 0.68 - 1.03 ] , p=0.089 ) . Preplanned subgroup analyses showed significantly longer survival in the gefitinib group than the placebo group for never-smokers ( n=375 ; 0.67 [ 0.49 - 0.92 ] , p=0.012 ; median survival 8.9 vs 6.1 months ) and patients of Asian origin ( n=342 ; 0.66 [ 0.48 - 0.91 ] , p=0.01 ; median survival 9.5 vs 5.5 months ) . Gefitinib was well tolerated , as in previous studies . INTERPRETATION Treatment with gefitinib was not associated with significant improvement in survival in either co primary population . There was pronounced heterogeneity in survival outcomes between groups of patients , with some evidence of benefit among never-smokers and patients of Asian origin Purpose Several cases have been reported in which central nervous system ( CNS ) metastases of non-small cell lung cancer ( NSCLC ) resistant to gefitinib were improved by erlotinib . However , there has been no study in which cerebrospinal fluid ( CSF ) concentrations of gefitinib and erlotinib are directly compared . Thus , we aim ed to compare them . Methods We examined 15 Japanese patients with NSCLC and CNS metastases with epidermal growth factor receptor gene mutations who received CSF examinations during epidermal growth factor receptor-tyrosine kinase inhibitors treatment ( 250 mg daily gefitinib or 150 mg daily erlotinib ) . Plasma and CSF concentrations were determined using high-performance liquid chromatography with t and em mass spectrometry . Results The concentration and penetration rate of gefitinib ( mean ± st and ard deviation ) in the CSF were 3.7 ± 1.9 ng/mL ( 8.2 ± 4.3 nM ) and 1.13 ± 0.36 % , respectively . The concentration and penetration rate of erlotinib in the CSF were 28.7 ± 16.8 ng/mL ( 66.9 ± 39.0 nM ) and 2.77 ± 0.45 % , respectively . The CSF concentration and penetration rate of erlotinib were significantly higher than those of gefitinib ( P = 0.0008 and < 0.0001 , respectively ) . The CNS response rates of patients with erlotinib treatment were preferentially ( but not significantly ) higher than those with gefitinib treatment . ( 1/3 vs. 4/7 , respectively ) . Leptomeningeal metastases in one patient , which were refractory to gefitinib , dramatically responded to erlotinib . Conclusions This study suggested that higher CSF concentration could be achieved with erlotinib and that erlotinib could be more effective for the treatment for CNS metastases , especially leptomeningeal metastases , than gefitinib A r and omized , open-label , 2-period crossover study was conducted to evaluate the bioequivalence of 6 tablets of erlotinib 25 mg and 1 tablet of erlotinib 150 mg ( arm A , n = 42 ) and the oral bioavailability of the 150-mg tablet versus a 25-mg intravenous infusion ( arm B , n = 20 ) in healthy subjects . The washout period was 2 weeks between treatments . Plasma concentrations of erlotinib and its active metabolite , OSI-420 , were measured after each dose . The ratios of geometric means for AUC(0-infinity ) and Cmax of erlotinib following 6 tablets of erlotinib 25 mg and 1 tablet of erlotinib 150 mg were ( 1 and 0.95 ) within the predefined bioequivalence range of 0.80 to 1.25 . The mean absolute oral bioavailability , using compartmental analysis , was estimated as 59 % ( 95 % confidence interval , 55%-63 % ) . Overall , 6 tablets of erlotinib 25 mg are bioequivalent to a single 150-mg tablet . Both intravenous and oral erlotinib were generally well tolerated with an estimated bioavailability of 59 % following oral administration |
10,352 | 26,385,620 | This may not hold true for fully edentulous patients in the maxilla .
In general , fully edentulous patients seem to opt for a fixed or removable rehabilitation on implants for specific reasons .
In these patients , the timing of implant placement does not seem to affect patient satisfaction .
Patients seem to prefer straightforward implant surgery over complex surgery that includes bone grafting .
Fully edentulous patients in the m and ible experience higher satisfaction with an IOD when compared to a CD . | AIM To provide an up date on the use of Patient-Reported Outcome Measures ( PROMs ) in the field of implant dentistry ( 1 ) ; to compare PROMs for prostheses supported by one or more implants to alternative treatment options or a healthy dentition ( 2 ) .
RESULTS With nearly half of the output ( 300 of 635 ) published in the last 6 years , there is a growing interest in PROMs by the scientific community . | OBJECTIVES the aim of this r and omized-controlled clinical trial was to compare the objective and subjective esthetic outcomes of two types of screwed-retained single-implant crowns . MATERIAL S AND METHODS participants were r and omly assigned to the test ( all-ceramic ) and control [ porcelain-fused-to-ceramic ( PFM ) ] groups and were seen under investigation at baseline ( B ) , crown insertion ( CI ) , 1-year follow-up ( 1Y ) , and 2-year follow-up ( 2Y ) . Objective parameters were assessed by an intra-oral digital photograph ( 1:1 ratio ) , a study cast , a st and ardized radiograph , periodontal/peri-implant measurements , and question naires were obtained for the subjective parameters . In addition , pink esthetic score ( PES ) and white esthetic score ( WES ) were calculated for both groups . For the subjective evaluation , a visual analogue scale ( VAS ) question naire was used to assess the level of patient satisfaction regarding the esthetic outcome . Then , nine expert clinicians visually inspected and assessed subjective evaluation at the professional level . Statistical analysis was used to compare between groups and investigational appointments . RESULTS twenty patients were included in the study , 10 allocated to the all-ceramic group and 10 to the PFM group . No statistically significant differences were observed for the objective measurements comparing the test and control groups . Minor chipping of the ceramic veneering material was observed in the two patients of control group . The mean difference for all groups comparing objective parameters revealed an increase of papilla height between time points . A slight recession ( 0.26 mm ) of the peri-implant mucosal margin at the implant site was observed between 1Y and 2Y . Mean values for PES and WES were 13.9 and 13.1 for the PFM group and for the all-ceramic group , respectively . These values were not statistically significant . Implant crown volume , outline , translucency , and characterization showed major discrepancies with the contra-lateral natural teeth . As for subjective parameters , VAS patients ' responses regarding their perceptions of the esthetic outcome showed no statistical differences between groups and clinicians ' accuracy scores were 50 % and 47 % for PFM and all-ceramic crowns , respectively . CONCLUSION PFM and all-ceramic single-implant restorations may be indistinguishable from each other regarding the objective /subjective assessment of esthetic integration . The material chosen for fabricating an implant crown per se does not ensure an optimal esthetic outcome if other esthetic parameters are not present INTRODUCTION Up-to- date studies comparing endodontic treatment versus implant-supported prosthesis have shown similar clinical outcome and survival rates . However , no data are available comparing both treatment modalities based on the patient 's perception of quality of life . This study was design ed to qualitatively describe and compare the quality of life of patients with restored , single endodontically treated teeth versus patients with single implant-supported fixed prostheses . METHODS Forty-eight patients agreed to participate in the study ( n = 24 from each treatment modality ) . Of those , 37 actually participated in the study : 17 were endodontically treated and 20 had an implant-supported prosthesis . Patients in each of the two groups were r and omly selected from the Graduate Endodontics and Graduate Periodontics Departments , respectively . Six focus group discussion s ( n = 3 per treatment group ) were held and audio-recorded for subsequent thematic analysis . Data were analyzed to identify common themes within each category and compared to assess any differences in quality of life between the two treatments . Additionally , a quality of life survey , the shortened version of the Oral Health Impact Profile ( OHIP-14 ) , was given before the discussion group and the responses analyzed . RESULTS The results obtained from this study show similar overall OHIP scores and show a high rate of satisfaction with both treatment modalities . Content analysis of the discussion groups revealed several themes and subthemes . The major themes were importance of overall health , financial implication s of the treatments , perception of the treatments and its outcomes , time since treatment , and follow-up dental visits . CONCLUSIONS The results help identify patients ' perception and concerns with each treatment modality and assist the clinician and patient in the selection of an optimal treatment for their given situation . In addition to the prognosis and outcomes , clinicians should consider patients ' perceptions and preferences as well as the influence each therapy may have on their quality of life , both short- and long-term . Overall , all the participants in this study were pleased with the treatment received and expressed a clear message to save their natural dentition whenever possible OBJECTIVE To evaluate and compare marginal bone loss around mini-implants supporting maxillary overdentures with either partial or full palatal coverage . METHOD AND MATERIAL S Nineteen edentulous patients complaining of retention problems involving their maxillary dentures were r and omly allocated in two groups . Group I ( n = 10 ) received maxillary dentures with full palatal coverage , and group II ( n = 9 ) received maxillary dentures with partial palatal coverage . In total , 114 mini-implants ( 6 per patient ) were inserted using the nonsubmerged flapless surgical approach and loaded immediately with maxillary overdentures . Each implant was evaluated at the time of initial prosthetic loading and at 6 , 12 , and 24 months thereafter . Radiographic evaluation was performed in terms of vertical and horizontal bone loss . Implant mobility ( via Periotest values ) was measured using a Periotest device , and patient satisfaction was evaluated with a visual analog scale . The cumulative survival rate was calculated using Kaplan-Meier analysis . RESULTS After 2 years , the mean vertical bone loss in groups I and II was 5.38 and 6.29 mm , respectively , while the mean horizontal bone loss in groups I and II was 1.52 and 1.93 mm , respectively . Most bone resorption occurred within 6 months after overdenture insertion in both groups . Group II recorded significant higher vertical bone loss and Periotest values than group I at all observation times . The cumulative survival rates of the mini-implants were 78.4 % and 53.8 % for groups I and II , respectively . All patients were satisfied with their maxillary overdentures in terms of retention and chewing ability . CONCLUSION Rehabilitation of edentulous maxillae with unsplinted mini-implants supporting overdentures and in particular with a combination of partial palatal coverage is not recommended because of excessive marginal bone resorption and the higher failure rate of mini-implants than was expected Background Very few studies on the impact of implant therapy on Oral Health Related Quality of Life ( OHRQoL ) in partially edentulous patients have been published . Aim This study aim ed at analysing the improvement of OHRQoL of patients who underwent dental implant treatment using the “ functional ” , “ psychosocial ” and “ pain and discomfort ” categories of the Geriatric Oral Health Assessment Index ( GOHAI ) . Methods Within a prospect i ve cohort of patients rehabilitated with Straumann dental implants , the OHRQoL of 176 patients ( 104 women and 72 men ) was assessed using the GOHAI question naire , at two different times , before and after implant placement . The degree of oral treatment was categorised into three classes : “ Single Tooth Implant ” ( n = 77 ) , “ Fixed Partial Denture ” ( n = 75 ) , “ Fixed or Retained Full Prostheses ” ( n = 24 ) . The participants ’ characteristics ( gender , age , tobacco habits , periodontal treatment , time between both evaluations ) were assessed . Results Before treatment , the GOHAI score was lower for participants with fewer teeth ( F = 19 , P < 0.001 ) . After treatment , no difference was observed between participants ; significant improvements were observed in the GOHAI scores obtained ( repeated measures , analysis , ( F = 177 , P < 0.001 ) ) for each of the GOHAI fields studied ( functional , psychosocial and pain & discomfort ) , regardless of the degree of treatment . The best improvement was observed in patients who needed complete treatment ( P < 0.001 ) . The presence of preliminary periodontal treatment , tobacco habits , age and gender of the participants did not have a significant impact on OHRQoL. Changing the time between the two evaluations ( before and after treatment ) had no impact on the changes in the GOHAI score . Conclusions Implants enhanced the OHRQoL of participants that needed oral treatment OBJECTIVES To study patient satisfaction and masticatory efficiency of single implant-retained m and ibular overdentures using the stud and magnetic attachments in a r and omized clinical trial with a crossover design . METHODS Patients received a single implant placed in the midline of the m and ible and either a stud ( Locator ) or a magnetic ( Magfit ) attachment , assigned at r and om . Patient satisfaction , including patient comfort , speech , chewing ability and retention , and masticatory efficiency measured by chewing peanuts , were assessed before and 3 months after attachment insertion . Patient satisfaction and masticatory efficiency were evaluated again 3 months after insertion of the alternate attachment bodies . The outcomes were compared before and after insertion of the attachments and between the two types of attachments using Wilcoxon signed rank tests . RESULTS Patient overall satisfaction , comfort , speech , chewing ability , and retention improved significantly after insertion of both types of attachment bodies ( p<0.05 ) . Masticatory efficiencies also increased in both the Locator and the Magfit groups ( p<0.05 ) . There were no statistically significant differences in patient overall satisfaction , comfort , speech , and retention between the two types of attachments ( p>0.05 ) . The Locator attachments performed better in perceived chewing ability than the Magfit ( p<0.05 ) , but there was no statistically significant difference in masticatory efficiency between the two attachment types ( p>0.05 ) . CONCLUSIONS Clinical outcomes were significantly improved in single implant-retained m and ibular overdentures using either the Locator or the Magfit magnetic attachments . There was no difference in masticatory efficiency between the two attachment types 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 Prosthetic outcome and patient satisfaction were evaluated in order to investigate whether there is a need or advantage to splint two implants in the m and ible retaining a hinging overdenture . This study included 36 fully edentulous patients r and omly divided into three groups according to the attachment system they received : magnets , ball attachments or straight bars ( reference group ) . None of the implants failed during the whole observation period in any of the groups . After 5 years of observation , the Bar group presented the highest retention capacity and the least prosthetic complications but revealed more mucositis and gingival hyperplasia . Patient satisfaction rated similar for all groups although the Magnet group showed lower retention forces . All patients would repeat the same treatment even though the majority of the Magnet group would prefer a more retentive solution because of limited denture stability BACKGROUND Patient-based outcomes with maxillary overdentures on a minimum number of implants , opposing m and ibular 2-implant overdentures are not evident in the literature . PURPOSE To evaluate patient 's satisfaction with maxillary 3-implant overdentures , opposing m and ibular 2-implant overdentures , using two different attachment systems over the first 2 years of service . MATERIAL S AND METHODS Forty participants wearing m and ibular 2-implant overdentures for 3 years were r and omly allocated to one of two similar implant system groups to receive maxillary 3-implant overdentures . Twenty participants were allocated to splinted and unsplinted attachment system treatment groups for each system . Patient satisfaction with pre-treatment complete maxillary dentures , with maxillary 3-implant overdentures at baseline and annually for 2 years , was measured using visual analogue scale question naires and the oral health impact profiles . Palatal coverage of the maxillary overdentures was reduced at the first annual recall . RESULTS Data showed significant improvement in pain reduction , comfort , stability , and function variables of the visual analogue scale after treatment . Analysis by prosthodontic design using visual analogue scale showed no significant difference . The total oral health impact profile-14 scores after treatment for all participants , regardless of prosthodontic design , were significantly lower ( more satisfied ) . The overall oral health impact profile-20E score at baseline was significantly higher ( more satisfied ) compared with pre-treatment conventional maxillary dentures . No significant changes were observed in the first or second years compared with baseline results . Twenty-two participants ( 84.6 % ) preferred reduced palatal coverage , regardless of prosthodontic design , after 1 year . Twenty participants ( 76.9 % ) still preferred reduced palatal coverage at the end of the second year . CONCLUSIONS The provision of maxillary 3-implant overdentures to oppose m and ibular 2-implant overdentures significantly improve levels of patient satisfaction compared with conventional maxillary dentures OBJECTIVE Comparing treatment outcome of four and six bar-connected implants in the anterior maxillary region to support an overdenture during a 1-year follow-up period . MATERIAL AND METHODS Fifty edentulous patients with lack of retention and stability of the upper denture , but with sufficient bone volume to place implants in the anterior maxillary region , were selected . R and omization assigned patients to either four or six implants . Implant survival , overdenture survival , clinical scores , radiographic bone height changes , and patients ' satisfaction were assessed . RESULTS Forty-nine patients ( one drop out ) completed the 1-year follow-up . After 1 year , implant survival was 100 % in the four implants group and 99.3 % in the six implants group ( one implant lost ) . Overdenture survival was 100 % in both groups . Mean clinical scores were low and did not differ between groups ( independent Student 's t-test ) . Mean marginal bone resorption was 0.24 ± 0.32 mm in the four implants group and 0.25 ± 0.29 mm in the six implants group . Patients ' satisfaction had improved in both groups ( paired Student 's t-test ) . CONCLUSION Bar-supported overdentures on four implants in the anterior maxillary region are not inferior to overdentures supported by six bar-connected implants . Implant survival was high , peri-implant conditions were healthy and patients ' satisfaction had increased significantly in both groups STATEMENT OF PROBLEM M and ibular implant overdentures provide improved treatment outcome than conventional denture therapy , but there is controversy as to which overdenture treatment is the best choice . PURPOSE This study evaluated 3 different m and ibular implant overdenture treatments with respect to prosthesis retention and stability , tissue response , patient satisfaction and preference , and complications to determine treatment outcomes . MATERIAL AND METHODS In a prospect i ve , r and omized clinical trial , using a crossover design , 30 subjects ( mean age , 58.9 ; 63 % male ) received 4 implants in the anterior m and ible . For each subject , 3 different overdenture attachment types were fabricated and /or fitted to the implants . These included a 4-implant bar attachment fitted to all 4 implants , a 2-implant bar attachment , and 2 independent ball attachments . Subjects were r and omly assigned to 1 of 6 possible treatment sequences and received all 3 attachment types each for approximately 1 year . Data were collected at baseline , and at 6 and 12 months for treatment types . Denture retention and stability and parameters of soft tissue response were recorded . Complications were documented and question naires were used to identify subject masticatory ability , denture complaints , and preferences . Data were analyzed to determine statistical equivalence among the 3 different treatments using the Schuirmann 's two one-sided test ( TOST ) procedure , and the Wilcoxon-Mann-Whitney TOST procedure ( α=.05 ) . RESULTS Force gauge prosthesis retention measurements showed that the 3 treatment types were not statistically equivalent , with the 4-implant bar demonstrating the greatest retention . Criterion-based retention scores were statistically equivalent for all treatments . Both the force gauge and criterion-based prosthesis stability measurements were statistically equivalent among all 3 treatment types . Analysis of all other multiple criterion-based scoring systems indicated the majority of these variables demonstrated equivalence . Where equivalence was not identified , the most favorable responses were typically found with the O-ring treatment , and the least favorable with the 4-implant bar treatment . From the small percentage of treatment visits demonstrating minor complications , no single treatment presented with greater complications than the others . For the treatment preference among subjects , 52 % selected the independent ball attachment , 32 % the 4-implant bar , and 16 % the 2-implant bar ( P=.10 ) . CONCLUSIONS The 2-implant independent treatment used in this study provided equivalent or more favorable treatment outcomes for most measured parameters relative to the more complex and costly 2- and 4-implant bar attachments . The 4-implant bar treatment provided greater prosthesis retention than the other treatment types in this study , but after experience with all systems , subjects were more satisfied with and preferred the independent implant treatment INTRODUCTION Tooth loss reduces oral-health-related quality of life ( OHRQoL ) as assessed with the 14-item Oral Health Impact Profile question naire ( OHIP-14 ) . OBJECTIVES This prospect i ve multicenter case-control study sought to ( i ) establish OHRQoL in patients requiring a single implant in the anterior maxilla and to ( ii ) compare these changes following implant placement and immediate provisionalization in extraction sockets with healed alveolar ridges up to 1 year . MATERIAL AND METHODS Ninety-six patients were enrolled in the study with 102 single implants ( OsseoSpeed AstraTech ) provisionalized immediately after placement in sockets or after placement in healed ridges . A final crown was cemented after 12 weeks . OHIP-14 was registered before surgery ( baseline ) , after 1 ( provisional crown ) , 6 and 12 months ( final crown ) . Repeated measures ANOVA was performed for the seven conceptual OHIP Domains , the treatment group ( extraction site socket vs. healed alveolar ridge ) and time as within subjects variables . RESULTS Two implants failed , 1/48 ( 2.1 % ) in the extraction group ( n=46 patients ) and 1/54 ( 1.8 % ) in the healed ridge group ( n=50 patients ) . From 82 patients ( 87.5 % ) , OHIP-14 was available at all time points . The overall OHIP-14 based on the mean of the seven domains increases between baseline and 6 months and remained stable afterward for the total study group and both treatment groups . Comparison between extraction and healed groups revealed no significant difference at baseline but the healed group showed a significantly higher improvement for functional limitation , physical disability , physical pain and psychological discomfort ( P<0.05 ) . Between baseline and 1 year in the healed bone group , all seven domains improved significantly compared with only three domains in the extraction group . However , the overall OHIP-14 score between groups was not substantially different . Hence , both treatment modalities lead to similar OHRQoL improvement . CONCLUSION Patients in need of a single-tooth replacement have limited OHRQoL problems as reflected by the OHIP-14 score but improvements in several domains related to oral health were evaluated when implants were placed and provisionalized in healed bone and extraction sites PURPOSE The purpose of this study was to compare elderly patients ' satisfaction and oral health-related quality of life with m and ibular two-implant overdentures and conventional dentures . MATERIAL S AND METHODS Sixty edentulous subjects aged 65 to 75 years were r and omly assigned to two groups treated with maxillary conventional dentures and either a m and ibular conventional denture ( n = 30 ) or an overdenture supported by two implants with ball retainers ( n = 30 ) . Subjects rated their general satisfaction , as well as other features of their dentures ( comfort , stability , ability to chew , speech , esthetics , and cleaning ability ) , prior to treatment and 2 months postdelivery . Changes in ratings on the original Oral Health Impact Profile ( OHIP ) and its short form ( OHIP-EDENT ) were also used as indicators of oral health-related quality of life . RESULTS The primary outcome of this study , ratings of general satisfaction 2 months postdelivery , was significantly better in the group treated with m and ibular two-implant overdentures ( P = .001 ) . In addition , the implant group gave significantly higher ratings on comfort , stability , and ability to chew . Furthermore , using OHIP-EDENT , subjects who received m and ibular two-implant overdentures had significantly fewer oral health-related quality of life problems than did the conventional group . CONCLUSION These short-term results suggest that m and ibular two-implant overdentures combined with maxillary conventional dentures provide better function and oral health-related quality of life than conventional dentures UNLABELLED Implant overdentures and conventional prostheses have been compared in several trials using a variety of functional and oral health-related quality of life ( OHQOL ) outcomes . In this paper , we describe the impact of implant overdentures on general and OHQOL in seniors . OBJECTIVES To compare the oral health-related and general quality of life of seniors ( aged 65 - 75 years ) who received either m and ibular implant overdentures or conventional dentures . METHODS Sixty edentulous patients were recruited . Thirty received m and ibular overdentures retained by two implants ( IOD ) and a conventional maxillary denture , the other 30 subjects received new maxillary and m and ibular conventional complete dentures ( CD ) . All completed the 20-item version of the Oral Health Impact Profile ( OHIP-20 ) before treatment , then at two and 6 months after delivery of the dentures . The SF-36 general health question naire was completed at baseline and 6 months only . RESULTS Pretreatment and 6-month data from 55 subjects were analyzed . Those who received the IODs had significantly better OHIP-20 total scores at 6 months . Results for IOD subjects were also superior in the functional limitation , physical pain , physical disability and psychological disability subscales . While no significant between group difference was found on the SF-36 health survey , significant pre-post-treatment differences within the IOD group were detected for the role emotional , vitality and the social function scales . CONCLUSIONS M and ibular overdentures retained by two implants provide elderly patients with better OHQOL . General health-related quality of life improved in the implant group PURPOSE The aim of this r and omized clinical trial was to compare the relative efficacy of m and ibular overdentures retained by only two implants and a bar attachment with conventional dentures . MATERIAL S AND METHODS Edentulous adults , aged 35 to 65 years , were r and omly assigned to two groups that received either a m and ibular conventional denture ( n = 48 ) or an overdenture supported by two endosseous implants with a connecting bar ( n = 54 ) . All subjects rated their general satisfaction and other features of their original dentures and their new prostheses ( comfort , stability , ability to chew , speech , esthetics , and cleaning ability ) on 100-mm visual analogue scales prior to treatment and 2 months postdelivery . Oral health-related quality of life was also evaluated pre- and posttreatment . RESULTS Multiple regression analysis revealed that the mean general satisfaction was significantly higher in the overdenture group than in the conventional denture group ( P = .0001 ) . Age , gender , marital status , and income were not significantly associated with ratings of general satisfaction . Furthermore , the implant group gave significantly higher ratings on three additional measures of the prostheses ( comfort , stability , and ease of chewing ; P < .05 ) . CONCLUSION A m and ibular two-implant overdenture opposed by a maxillary conventional denture is a more satisfactory treatment than conventional dentures for edentulous middle-aged adults PURPOSE To analyze maintenance service of fixed maxillary prostheses and overdentures based on conventional gold bars or titanium bars and frameworks fabricated with computer-aided design /computer-assisted manufacture ( CAD/CAM ) technology . MATERIAL S AND METHODS Forty-one patients participated ; 16 received an implant overdenture with a gold bar ( gold OD ) , 12 received a CAD/CAM-fabricated implant OD with a titanium bar ( Ti OD ) , and 13 received a CAD/CAM implant-supported fixed prosthesis ( IFP ) . The bars and frameworks were screw-retained at the implant level . Maintenance service performed during the first 2 years was recorded and compared between the three groups . After this 2-year period , the Oral Health Impact Profile ( OHIP ) was administered . RESULTS For ODs ( gold , Ti ) most service consisted of activation of the matrices . Fractures of matrices and bar extensions occurred only in the gold OD group , and 65 % of these patients exhibited hyperplasia of the peri-implant mucosa . The maintenance rates were 1.24 ( gold OD ) , 1.36 ( Ti OD ) , and 0.98 ( IFP ) . These differences were not statistically significant . Retightening of occlusal screws was not necessary in any group . The probability that a complication occurred in the first year was high ( 60 % to 70 % ) and statistically not different between the three groups . The probability that a second complication occurred was significantly lower for the IFP group versus the gold OD group . The mean OHIP values were 1.7 ( IFP ) , 6.7 ( gold OD ) , and 7.3 ( Ti OD ) ; ratings in the IFP group were significantly better . CONCLUSIONS Maintenance service was typical for implant prostheses in the edentulous maxilla . Direct screw retention at the implant level without abutments had a favorable effect in all groups . A trend toward a reduction in problems was observed with the CAD/CAM superstructures . The OHIP confirmed high satisfaction , but quality of life appeared to be slightly higher with fixed prostheses Dental implants provide patients with restorative options for the edentulous maxilla . Both fixed and removable prostheses can be attached to the edentulous maxilla , but the efficacy of different design s has not been determined . In this two-session within-subject crossover trial we compared maxillary implant retained fixed prostheses with removable implant overdentures opposed by m and ibular implant-supported overdentures . Sixteen patients , who had previously received m and ibular implants , entered the study and received four to six maxillary implants . After dropouts as a consequence of a lack of osseointegration and general health problems , 13 remained . Of these , five received the removable prosthesis first and eight the fixed prosthesis . After 2 months , the prostheses were exchanged and the second was also worn for 2 months . Psychometric measurements of general satisfaction with the prostheses as well as comfort , ability to speak , stability , esthetics , ease of cleaning and occlusion were obtained once each prosthesis had been worn for 2 months . Chewing ability was assessed for seven types of food . Removable long-bar overdentures received significantly higher ratings of general satisfaction than fixed prostheses ( P = 0.003 ) . Patients also rated their ability to speak and ease of cleaning significantly better with the removable overdentures . Nine patients chose to keep the removable prosthesis and four preferred to keep the fixed prosthesis . The results suggest that maxillary removable overdentures on multiple implants may provide patients with better function than fixed prostheses OBJECTIVE The aim of this 5-year prospect i ve comparative study was to evaluate treatment outcome ( survival rate , condition of hard and soft peri-implant tissues , patient satisfaction , prosthetic and surgical aftercare ) of m and ibular overdentures supported by two or four implants . MATERIAL AND METHODS Sixty edentulous patients with a m and ibular height between 12 and 18 mm participated . Thirty patients were treated with an overdenture supported by two IMZ implants ( group A ) and 30 patients were treated with an overdenture supported by four IMZ implants ( group B ) . St and ardised clinical and radiographic parameters were evaluated 6 weeks after completion of the prosthetic treatment and after 1 , 2 , 3 , 4 and 5 years of functional loading . Prosthetic and surgical aftercare was scored during the evaluation period . RESULTS One implant was lost ( group A ) during the healing period . There were no significant differences with regard to any of the studied clinical or radiographic parameters of the peri-implant tissues between the groups . None of the patients reported sensory disturbances in the lip or chin region . No differences in satisfaction were observed between the groups . With regard to aftercare , there was a tendency of a greater need of prosthetic interventions in group A , while correction of soft-tissue problems was restricted to patients of group B. CONCLUSION There is no difference in clinical and radiographical state of patients treated with an overdenture on two or four implants during a 5-year evaluation period . Patients of both groups were as satisfied with their overdentures PURPOSE This study aim ed to compare the prosthetic aspects and patient satisfaction with prosthetic care in two-implant-retained m and ibular overdentures , whether implants were splinted with a bar or left with magnets or ball attachments . MATERIAL S AND METHODS Thirty-six completely edentulous patients had two Brånemark implants placed in the m and ibular canine area . A r and omized procedure allocated patients into three groups of equal size , each with a different attachment system : bars , magnets , or balls . Prosthesis retention and mechanical as well as soft tissue complications were recorded in addition to patient satisfaction . A linear mixed model was fitted with attachment type and time as classification variables and adjusted by Turkey 's multiple range test . RESULTS Ball-retained overdentures showed at year 10 the greatest vertical retention force ( 1,327 g ) , followed by bars ( 1,067 g ) and magnets ( 219 g ) . In the ball group , need for tightening of abutment screws was the most common mechanical complication ; in the magnet and bar groups , respectively , the most common complications were wear and corrosion , and the need for clip activation . Prosthesis stability and chewing comfort for the overdenture were rated significantly lower for the magnet group compared to the ball and bar groups . Prosthesis stability of the maxillary denture was rated significantly lower in the bar group compared to ball and magnet groups . CONCLUSION The ball group scored best in relation to retention of the overdenture , soft tissue complications , and patient satisfaction at year 10 . The bar group scored lower for comfort and stability of the maxillary denture . Magnets offered patients the least comfort PURPOSE To evaluate the medium-term effectiveness of 6.5 mm-long flapless-placed single implants immediately or early loaded at 6 weeks . MATERIAL S AND METHODS Thirty patients received two single NanoTite external hex Biomet 3i implants each , which were then r and omly allocated to be immediately or early loaded according to a splitmouth design . Implants had to be inserted with a minimum torque of > 40 Ncm . Provisional crowns were put in slight occlusal contact and replaced by definitive crowns 3 months after loading . Patients were followed for 4 years after loading . Outcome measures were implant failures , biological and biomechanical complications , peri-implant marginal bone level changes , and patient preference . RESULTS Twenty-nine implants were immediately loaded and 31 early loaded . Four years after loading , no drop-outs occurred . One implant failed in each group within 2 months after loading . Seven patients experienced complications at immediately loaded implants and 6 at early loaded implants . There were no statistically significant differences between groups for implant losses , complications , mean marginal bone level changes and patient preference . CONCLUSIONS Flapless-placed 6.5 mm-long single implants can be immediately loaded and remain successful up to 4 years after loading . Even longer follow-ups are still needed to evaluate the longterm prognosis of short implants PURPOSE To evaluate the efficacy of 7-mm-long flapless placed single implants immediately or early loaded at 6 weeks . MATERIAL S AND METHODS Thirty patients received two single Nanotite External Hex Biomet 3i implants that were then r and omised for immediate or early loading . All implants had to be inserted with a minimum torque > 40Ncm . Provisional crowns were put in slight occlusal contact and replaced by definitive crowns 3 months after loading . Outcome measures were implant failures , biological and biomechanical complications , peri-implant marginal bone level changes and patient preference . RESULTS Twenty-nine implants were immediately loaded and 31 early loaded . Thirteen flaps had to be elevated in 12 patients . Eleven implants in ten patients did not reach the planned insertion torque . Eight implants in seven patients were immediately replaced by implants with a larger diameter , two were loaded anyway , and one implant that was r and omised to immediate loading was early loaded instead . Nine months after loading , no drop-out occurred . One implant failed in each group . There were no statistically significant differences between groups for implant losses , complications , mean marginal bone level changes , and patient preferences . CONCLUSIONS Flapless placed 7-mm-long single implants can be successfully loaded the day of insertion . Longer follow-ups are needed to monitor the long-term prognosis of short implants PURPOSE The objective of this prospect i ve study was to assess the overall outcome of immediate single implant treatment in the anterior maxilla after a 3-year observation period . MATERIAL AND METHODS Thirty consecutively treated patients with a thick gingival biotype , ideal gingival level/contour and intact socket walls at the time of tooth extraction were treated for single-tooth replacement in the aesthetic zone by two experienced clinicians . Treatment included minimal mucoperiosteal flap elevation , immediate implant placement ( NobelReplace TiUnite ( ® ) ) , insertion of a grafting material between the implant and the socket wall and connection of a screw-retained provisional restoration . The latter was replaced by a cemented crown 6 months thereafter . Patients were clinical ly and radiographically re-examined after 3 years to assess implant survival , complications and hard and soft tissue conditions . The aesthetic outcome was objective ly rated using the Pink Esthetic Score ( PES ) and White Esthetic Score ( WES ) by a blinded clinician who had not been involved in the treatment . RESULTS Twenty-five patients could be re-evaluated after 3 years . One early implant failure had occurred result ing in an implant survival rate of 96 % . Radiographic examination yielded on average 1.13 mm mesial , respectively 0.86 mm distal bone loss . The clinical conditions showed fairly low peri-implant plaque ( 18 % ) and bleeding ( 24 % ) and mean probing depth was 3.17 mm . Mean mesial/distal papilla shrinkage and midfacial soft tissue recession in reference to the pre-operative status accounted for 0.05 , 0.08 and 0.34 mm , respectively . Between the 1- and 3-year re assessment mesial papillae showed significant re-growth ( 0.36 mm ; p=0.015 ) . Advanced midfacial recession ( > 1 mm ) was found in 2/25 ( 8 % ) cases . Five ( 21 % ) cases were aesthetic failures ( PES<8 and /or WES<6 ) and 5/24 ( 21 % ) showed an ( almost ) perfect outcome ( PES≥12 and WES≥9 ) . The remainder ( 14/24 or 58 % ) demonstrated acceptable aesthetics . CONCLUSIONS The proposed strategy seems a valuable and predictable treatment option for well-selected patients in the mid-long term as shown by almost full papillary re-growth and a low risk for advanced midfacial recession This study is a two-center clinical trial with the aim to assess the treatment effects of implant-retained m and ibular overdentures versus conventional complete dentures . Treatment had been assigned according to a balanced allocation method . The following criteria were used to enhance the comparability of the treatment groups : age , gender , the edentulous period of the m and ible , the number of previously made m and ibular dentures , the number of years having worn the present m and ibular denture and the symphyseal bone height . 151 patients with severely resorbed m and ibles participated in the study , they were treated at two centers . Ninety-one patients received an implant-retained m and ibular overdenture ( IRO ) and 60 patients a conventional complete denture ( CD ) . Since some patients refused the allocated treatment the " Intention To Treat " principle was applied . This implies that patients are evaluated in the originally allocated treatment group regardless of the actual treatment they received . Patient 's experiences were evaluated before treatment and 1 yr after insertion of the new dentures . Results before treatment showed that both treatment groups were comparable : they were dissatisfied with their m and ibular denture and they could hardly chew tough or hard foods . One year after insertion of the new dentures the IRO-group was satisfied with their m and ibular denture , whereas only one third of the CD-group was satisfied . With respect to the chewing ability the IRO-group scored significantly better than the CD-group(P<0.0001 ) Although previous studies have demonstrated that implant-supported prostheses are more satisfactory and efficient for edentulous patients than are conventional prostheses , until now no investigation has directly compared different types of implant-supported prostheses . We carried out a within-subject cross-over clinical trial with fixed and long-bar removable implant-supported m and ibular prostheses . Fifteen subjects were r and omly divided into two groups . One group received the fixed prosthesis first , while the other first received the removable . After a two-month adaptation period , psychometric measurements of various aspects of the prostheses and physiological tests of masticatory efficiency were carried out . The prostheses were then changed , and the procedures repeated . At the end of the study , subjects chose the prosthesis they wished to keep . In this paper , we report on the data gathered at this last appointment . Eight subjects chose the fixed ( F group ) , and seven chose the removable ( R group ) . Both groups rated stability and ability to chew with the fixed as significantly better than with the removable . However , the R group rated ease of cleaning as the most important factor governing their decision , followed by esthetics and stability . The F group considered stability to be the most important factor in their decision , followed by chewing ability and ability to clean . There was a tendency for the removable to be chosen by older subjects ( + 50 years ) . These results suggest that patients choose fixed or removable implant-supported prostheses for specific reasons , and that patient attitudes should be considered when the design of a prosthesis is being planned for an individual patient 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 study was to establish the treatment outcome of full denture treatment with or without implant support , in which the outcome assessment focuses on the patient 's subjective evaluation ( ' denture-satisfaction ' ) . DESIGN A multicenter r and omized clinical trial . SUBJECTS Thirty-two men and 118 women ( mean age 56 + /- 9 , range 35 - 84 years ) participated in the study . The mean height of the m and ible was 13 + /- 2 mm , measured on a lateral cephalometric radiograph . The patients were r and omly assigned to either a group treated with implant-retained m and ibular overdentures and a new maxillary denture , or to a control group treated with a new set of complete dentures . MAIN OUTCOME MEASURES Denture satisfaction was assessed using question naires focusing on denture-related complaints and ' a general satisfaction rate ' . RESULTS Based on the baseline data , from the ' denture complaints ' question naire six interpretable factors could be extracted . One factor did not vary following treatment and was excluded from the outcome analysis . At the 1-year evaluation three out of five factors showed significantly better scores for the group treated with implants than for the control-group . The same was found for the general satisfaction rate . CONCLUSION For patients with a severely resorbed m and ible , overdentures retained by dental implants appear to provide a more satisfactory solution to their denture-related problems PURPOSE The aim of this r and omised controlled trial was to assess the clinical performance of single crowns in the posterior maxilla supported by either 6-mm or 11-mm implants combined with maxillary sinus floor elevation . MATERIAL S AND METHODS 41 consecutive patients with one missing premolar or molar in the posterior maxilla and with an estimated bone height of 6 to 8 mm in that area were included . Each patient was r and omly allocated to one of the two treatment groups , namely to receive an 11-mm implant ( Osseo Speed 4.0 S , Dentsply Implants , Mölndal , Sweden ) in combination with maxillary sinus floor elevation surgery or to receive a 6-mm implant ( Osseo Speed 4.0 S ) without any grafting . After a 3-month osseointegration period , all implants were restored with custom-made titanium abutments and cemented zirconia-based porcelain crowns . Outcome measures were : implant survival ; radiographic bone changes ; plaque accumulation ; bleeding tendency ; peri-implant inflammation ; presence of dental calculus ; biological and technical complications ; and patients ' satisfaction . Clinical and radiographic examinations were performed at placement of the crown and 12 months thereafter . Patients ' satisfaction was scored before treatment and after 12 months of functioning of the crown . RESULTS One patient of the 11 mm implant group died during the follow-up . No implant failed and no biological or technical complications occurred . From loading to the 12 months follow-up , no difference was found in mean marginal bone changes between the groups ( bone resorption in both groups 0.1 ± 0.3 mm ) . Clinical items revealed very healthy peri-implant soft tissues in both groups . Patients ' satisfaction scores were high in both groups . CONCLUSIONS 6-mm implants and 11-mm implants combined with sinus floor elevation surgery are equally successful to support a single crown in the resorbed posterior maxilla after 1-year follow-up Treatment of lower denture complaints of patients with an edentulous m and ible with a height of at least 15 mm can consist of meticulous construction of a new set of dentures ( CD ) , construction of a new set of dentures following preprosthetic surgery to enlarge the denture-bearing area ( PPS ) , or construction of an implant-retained m and ibular overdenture ( IRO ) . The aim of this prospect i ve r and omized controlled clinical trial was to evaluate the satisfaction of the above mentioned treatment modalities in resolving lower denture related complaints . Ninety edentulous patients ( Cawood class IV and V , mean m and ibular height 20.7 + /- 2.7 mm ) were r and omly assigned to one of these treatment modalities . The main outcome parameters were denture satisfaction and chewing ability , which were assessed using vali date d self-administered question naires focusing on denture-related complaints and problems with chewing different types of food . These parameters were measured before treatment , and 1 , 5 and 10 years after treatment . Differences among the three groups were tested by applying a one way analysis of variance and a Tukey 's test for multiple comparison . At the 1 year evaluation , significantly better scores were observed in the two surgical groups ( IRO , PPS ) than in the CD group ( P<0.05 ) . At 5 year evaluation the ' complaints of the lower denture ' showed a significantly better score in the IRO group when compared to the PPS and CD groups ( P<0.05 ) . No significant differences were observed between the PPS and CD group . At 10 year evaluation , the intention to treat analysis revealed no significant differences between the three groups , while a per protocol analysis showed that the IRO group was the most satisfied . From this study it is concluded that both on the short and long term denture satisfaction appears most favourable in the IRO group when compared to the PPS and CD groups . Implant-retained overdentures are , therefore , a favourable treatment modality for edentulous patients with lower denture problems Studies have shown that m and ibular implant overdentures significantly increase satisfaction and quality of life of edentulous elders . Improved chewing ability appears to have a positive impact on nutritional state . Therefore , it is important to determine the best design of this prosthesis over the long term . In this r and omized controlled trial , three groups of edentulous participants with atrophic m and ibles wore 3 types of implant overdentures . During an eight-year follow-up , only seven of the 110 participants had dropped out of this study . Almost all participants were still satisfied with their overdentures . Participant satisfaction concerning retention and stability of the m and ibular overdenture had decreased significantly in the two-implant ball attachment group , whereas the opinion of participants in the single- and triple-bar groups was still at the same level . The long-term results suggest that a m and ibular overdenture retained by 2 implants with a single bar may be the best treatment strategy for edentulous people with atrophic ridges The aim of this research was to compare the accuracy outcomes of open- and closed-tray implant impressions for partially edentulous patients . Eleven partially edentulous spaces in seven patients with two existing implants for fixed partial dentures were included . Group I ( closed-tray ) and group II ( open-tray ) were compared using microcomputed tomography scanning . No statistically significant differences were found between the closed- and open-tray techniques ( P = .317 ) . The subjective evaluation of patient comfort showed no differences with either impression technique . There were no differences seen between open- and closed-tray impression techniques in partially edentulous patients when implants had less than 10 degrees of angulation PURPOSE The aim of this prospect i ve r and omized clinical trial was to evaluate 10 years of treatment of patients receiving a m and ibular implant-retained overdenture ( IRO ) or a conventional complete denture ( CD ) . MATERIAL S AND METHODS One hundred twenty-one edentulous patients were treated with an IRO ( 2 endosseous implants , n = 61 ) or a conventional CD ( n = 60 ) . Clinical aspects and patient satisfaction were evaluated . One year after placement of the denture , unsatisfied patients of the CD group were given the opportunity to receive implants . RESULTS In the IRO group , 4 implants were lost during the first year and 4 implants were lost during the next 4 years . Between 5 and 10 years , no implants were lost ( survival rate : 93 % ) . In the CD group , 24 patients ( 40 % ) chose an IRO between 1 and 10 years . DISCUSSION Patients in the IRO group were significantly more satisfied than patients in the CD group after 1 year ( satisfaction score 8.3 versus 6.6 on a scale of 1 to 10 ) , after 5 years ( 7.4 versus 6.4 ) , and after 10 years ( 7.7 versus 6.8 ) . CONCLUSION The mean satisfaction score of the CD group ( including patients who later received implants ) was still lower than that of the IRO group , in spite of the opportunity for retreatment with IROs . Endosseous implants had a high survival rate after 10 years of follow-up In a within-subject cross-over clinical trial , psychometric and functional measurements were taken while 15 completely edentulous subjects wore m and ibular fixed prostheses and long-bar removable implant-supported prostheses . In this paper , the results of a psychometric assessment are presented . Eight subjects first received the fixed bridge and seven the removable type . After having worn a prosthesis for a minimum of two months , subjects responded to psychometric scales that measured their perceptions of various factors associated with prostheses . They also chewed test foods while masticatory activity was recorded . The prostheses were then changed and the procedures repeated . At the end of the study , patients were asked to choose the prosthesis that they wished to keep . Patients assigned significantly higher scores , on visual analogue scales , to both types of implant-supported prostheses than to their original conventional prostheses for all factors tested , including general satisfaction . However , no statistically significant differences between the two implant-supported prostheses were detected except for the difficulty of chewing carrot , apple , and sausage . For these foods , the fixed prostheses were rated higher . Subjects ' responses to category scales were consistent with their responses to the visual analogue scales . These results suggest that , although patients find the fixed bridge to be significantly better for chewing harder foods , there is no difference in their general satisfaction with the two types of prostheses OBJECTIVE To evaluate the masticatory efficiency of patients rehabilitated with conventional dentures ( CDs ) or implant-retained m and ibular overdentures . BACKGROUND Despite the evident benefits of implants on mastication as assessed by subjective patient-based outcomes , the extent of implant overdenture treatment effect on food comminution is not well established . MATERIAL S AND METHODS A r and omised clinical trial was carried out with 29 completely edentulous patients divided into two groups . The first group was rehabilitated with a m and ibular overdenture retained by two splinted implants with bar-clip system , while the second group was rehabilitated with a m and ibular CD . Both groups also were rehabilitated with maxillary CDs . Masticatory efficiency and patient satisfaction were assessed 3 months after denture insertion . Masticatory efficiency was evaluated through the colorimetric method with the beads as the artificial test-food . Comparisons for masticatory efficiency and patient satisfaction were performed using Student 's t-test ( α = 0.05 ) . RESULTS No significant statistical difference was found for masticatory efficiency ( p = 0.198 ) . Patient overall satisfaction was significantly higher for the m and ibular overdenture ( p < 0.001 ) . In addition , m and ibular overdenture patients were significantly more satisfied with chewing experience ( p < 0.05 ) and retention of the lower denture ( p < 0.005 ) . CONCLUSION The results of this study suggest that m and ibular overdenture significantly improves chewing experience , although limited effect on masticatory efficiency has been observed 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 AIM To evaluate the aesthetic outcomes of zirconia versus titanium abutments for single tooth implant-supported crowns in the anterior maxilla . MATERIAL & METHODS A parallel , double blind clinical trial was conducted at the Complutense University ( Madrid ) , where 38 patients were recruited . After r and om allocation ( via computer-generated permuted blocks ) , either zirconia ( test ) or titanium ( control ) abutments were placed . Intra- and inter-group differences in aesthetic ( main outcome ) , clinical , radiographical , and patient-centred outcomes were evaluated at baseline ( crown placement ) and at 1-year follow-up . RESULTS At 1 year , 25 of the 30 r and omized patients were analysed ( 11 test and 14 control ) . Using the Implant Crown Aesthetic Index ( ICAI ) , the scoring at baseline and 1-year were 7.9 and 7.6 for the test group and 10.6 and 11.3 for the control group , respectively . These differences were not statistically significant ( sample size non-contrasted ) . Patient satisfaction was similarly high in both groups ( visual analogue scale 8.5 ) . Furthermore , no differences were observed in the clinical or radiographical outcomes . Two abutment fractures were registered in the test group . CONCLUSIONS The use of zirconia abutments demonstrated a tendency towards better aesthetic outcomes although the differences were not statistically significant . However , more technical complications were noted with the use of zirconia abutments The aim of this study was to evaluate the self-aligning overdenture attachment system by comparing its oral health-related quality of life ( OHRQL ) with a traditionally used ball attachment system . In this r and omized , within-subject crossover trial , 25 edentulous subjects each received 2 m and ibular implants , and were then assigned to receive either self-aligning or traditional ball attachments . After 3 months , all subjects were switched to the second attachment type . The OHRQL was evaluated for both of the treatments using the short form of the Oral Health Impact Profile ( OHIP-14 ) . A sub analysis among subjects with below-average space available for attachment placement was also performed . Wilcoxon signed-rank test was used to compare differences between groups . Scores on the OHIP-14 physical disability domain were significantly better for the self-aligning attachment system ( P = .049 ) . Among subjects with below-average attachment space , functional limitation , psychological discomfort , physical disability , psychological disability , and total OHIP-14 , scores were significantly better for the self-aligning attachment system ( P = .041 , P = .047 , P = .048 , P = .026 , and P = .005 , respectively ) . The self-aligning attachment system for 2-implant-retained m and ibular overdentures is equal or superior to traditional ball attachments in all domains of the OHIP-14 The objective of the present report was to study the effect of implant treatment on subjective parameters in edentulous patients with an extremely resorbed m and ible . Three different treatment modalities to support an overdenture were compared : transm and ibular implant according to Bosker , augmentation of the m and ible followed by four endosseous implants , and the insertion of four short endosseous implants . Sixty patients [ 50 women and 10 men , mean ( + /- SD ) age 59 ( + /- 11 ) years ] met the inclusion criteria and were assigned in one of the three treatment groups . Before treatment and 12 months after placement of the new overdentures , denture satisfaction , psychosocial aspects and experiences during the surgical phase were assessed with a battery of question naires . After 1 year , 58 patients were available for evaluation : one patient had died , and one patient had moved out of the region . There was a significant improvement of patient satisfaction and psychosocial functioning in all three treatment groups . At the 1-year evaluation , differences amongst the three groups were not significant . However , in terms of discomfort and pain during the surgical phase as well as the length of this phase ( at least 6 months ) , the augmentation using an autologous bone graft from the iliac crest followed by inserting four endosseous implants 3 months later appeared the least favorite option of the three modalities studied PURPOSE To compare the effectiveness of immediate post-extractive single implants with delayed implants placed in preserved sockets after 4 months of healing . Implants that achieved an insertion torque of at least 35 Ncm were immediately non-occlusally loaded . MATERIAL S AND METHODS Just after tooth extraction and in the presence of a loss of the buccal plate bone less than 4 mm , compared to the palatal wall , 106 patients requiring a single immediate postextractive implant in the maxilla from second premolar to second premolar were r and omly allocated to immediate implant placement ( immediate group ; 54 patients ) or to socket preservation using anorganic bovine bone covered by a resorbable collagen barrier ( delayed group ; 52 patients ) according to a parallel group design at three different centres . Bone-to-implant gaps were to be filled with anorganic bovine bone , however this was not done in 17 patients ( corresponding to 40 % of those who should have been grafted ) . Four months after socket preservation , delayed implants were placed . Implants placed with an insertion torque > 35 Ncm were immediately loaded with non-occluding provisional single crowns , replaced , after 4 months , by definitive crowns . Outcome measures were implant failures , complications , aesthetics assessed using the pink esthetic score ( PES ) , and patient satisfaction , recorded by blinded assessors . All patients were followed up to 4 months after loading . RESULTS Nineteen ( 35 % ) implants were not immediately loaded in the immediate group versus 39 ( 75 % ) implants in the delayed placement group because an insertion torque > 35 Ncm could not be obtained . No patient dropped out . Two implants failed in the immediate group ( 4 % ) versus none in the delayed group . More minor complications occurred in the immediate group ( 8) than the in the delayed group ( 1 ) and this was statistically significant ( P = 0.032 ) . At delivery of definitive crowns , 4 months after loading , aesthetics were scored as 12.8 and 12.6 in the immediate and delayed groups , respectively . There was no statistically significant difference ( P = 0.5 ) . Patients of both groups were equally satisfied . CONCLUSIONS There were more complications at immediate post-extractive implants when compared to delayed implants . The aesthetic outcome appears to be similar for both groups and it seems more difficult to obtain a high insertion torque in sockets preserved with anorganic bovine bone The purpose of this study was ( 1 ) to investigate denture satisfaction following the conversion of existing m and ibular complete dentures to implant overdentures ( IOD ) in very old edentulous patients who depend on help for activities of daily living and ( 2 ) to evaluate secondary end points , such as functional , structural , nutritional , and patient-centered aspects . For this r and omized clinical trial , 2 interforaminal short implants were placed in the intervention group ( n = 16 , 85.0 ± 6.19 yrs ) to retain m and ibular IODs ; the control group ( n = 18 , 84.1 ± 5.55 yrs ) received conventional relines . During the first year , no implant was lost ; however , 2 patients died . IODs proved more stable , and participants in the intervention group demonstrated significantly higher denture satisfaction as well as an increased oral health – related quality of life compared to the control group . Maximum voluntary bite force improved significantly with IODs , yet the chewing efficiency was not different between groups . Masseter muscle thickness increased with IODs , mainly on the preferred chewing side . Body mass index decreased in both groups , but the decline tended to be smaller in the intervention group ; blood markers and the Mini Nutritional Assessment did not confirm this tendency . These results indicate that edentulous patients who depend on help for activities of daily living may benefit from IODs even late in life ( Clinical Trial.gov NCT01928004 ) 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 BACKGROUND There is a lack of clinical studies on the self-aligning attachment system ( Locator(R ) ; Zest Anchors , Inc. homepage , Escondido , CA , USA ) for two-implant-retained overdentures in the edentulous m and ible . Therefore , a comparison of the Locator with two traditional design s ( a rotational gold matrix and a rubber O-ring type ) in clinical 1-year use was conducted . MATERIAL S AND METHODS From 2003 to 2007 , 60 patients received two Osseotite(R ) TG St and ard implants ( BIOMET 3i Implant Innovations , Palm Beach Gardens , FL , USA ) in the intraforaminal area of the edentulous m and ible . The implants were left unloaded for 3.5 months , r and omized to three different attachment systems , and loaded through a m and ibular overdenture . Twenty-three patients received a self-aligning attachment system ( Locator ) and 33 patients a ball attachment ( Dal-Ro(R)[BIOMET 3i Implant Innovations]n = 25 ; TG-O-Ring(R)[Cendres & Metaux SA , Biel-Bienne , Switzerl and ] n = 8) . After 12 months of delivery of the overdentures , the oral situation was evaluated : prosthodontic maintenance and biologic complications , subjective patients ' experience , and oral health-related life quality ( Oral Health Impact Profile [ OHIP-G 49 ] ) . RESULTS After 1-year of clinical service , 8 of 120 implants were lost ( 9.6 % ) . The Locator system brought up 34 prosthetic complications , especially the need for change of the male parts or activation because of loss of retention . The TG-O-Ring patients showed 14 complications , most of them the change of the O-Rings . The patients with the Dal-Ro abutment had seven minor complications in 12 months of clinical use . Biologic complications and patients ' oral health-related life quality showed no significant difference among the three experimental groups . CONCLUSIONS Prosthodontic maintenance was restricted to loss of retention for all systems . Within the observation period of this study , the self-aligning attachment system showed a higher rate of maintenance than the ball attachments . The patients ' oral health-related life qualities as well as the biologic parameters do not differ when using the three abutment systems STATEMENT OF PROBLEM The functional benefits of replacing old dentures with new conventional m and ibular dentures or implant-supported overdentures has not been fully determined . PURPOSE This study assessed the impact of these 2 types of replacement dentures on the food choices of diabetic patients . MATERIAL AND METHODS A total of 68 diabetic patients with original complete dentures participated in this study . Diabetes was controlled with insulin in 38 patients ( IT ) and without insulin in 30 patients ( NIT ) . All subjects received conventional maxillary dentures ; 25 received m and ibular conventional dentures ( CD ) , and 43 received overdentures with plastic clips and a Hader bar attached to 2 osseointegrated implants ( IOD ) . Subjects rated their perceptions of taste acceptability , texture acceptability , and chewing ease on a 4-point nominal scale and eating frequency on a 5-point scale for 13 specific foods at baseline ( with original dentures ) and at 6 months post-treatment completion ( PTC ) . Fisher exact tests were used to compare the change in percentage distributions of responses with treatment . A 2 x 2 x 2 repeated- measures analysis of variance ( ANOVA ) was performed to compare mean scores between the 2 denture groups , 2 diabetic groups , and 2 time intervals for each of the 13 foods and 4 questions related to food acceptability . RESULTS At baseline , no significant differences were found between the frequency distributions of responses in the CD and IOD groups or the IT and NIT groups for all 52 comparisons . With both types of study dentures , a higher percentage of patients perceived deterioration rather than improvement in function . When percentage distributions based on actual positive or negative change ( treatment effect ) in patient responses were compared , significant differences were found for 3 of the 52 responses , in favor of the IOD group . ANOVA demonstrated significant mean differences for 4 of the 52 comparisons . CONCLUSION Both types of study dentures result ed in declines in the perceived taste and texture acceptability of almost all test foods . Declines in perceived chewing ease and eating frequency were more common and greater in the CD than in the IOD group . Both types of study dentures failed to affect food choices , as evidence d by declines or limited improvement in the perceived frequency with which most foods were eaten AIM To analyse the patients ' perception of implant therapy , 10 years following installation of titanium oral implants . MATERIAL AND METHODS As a part of a prospect i ve cohort study of patients with ITI(R ) dental implants , 104 patients were recruited to answer a question naire with 13 statements on the subjective perception of implant treatment , 5 - 15 years after implant installation ( mean : 10.2 years ) . In addition , the patients were asked to mark a visual analogue scale ( VAS ) in which 0 indicated " total discontent " and 100 " total satisfaction " with the statements mentioned in the question naire . Results from the qualified questions answered were then compared with those obtained from VAS analysis . RESULTS One hundred and four patients , with 214 installed oral implants participated . Forty-eight percent of the implants were reconstructed with single crowns and 52 % with fixed partial dentures ( FPD ) . The cumulative survival rate of the implants at 10 years was 93 % . Two of the statements addressing function and chewing comfort yielded very high patient satisfaction ( 97 % highly satisfied or satisfied , mean VAS : 94+/-13 ) . Comparing chewing comfort for teeth or implants , respectively , 72.1 % perceived no difference between the two , 17.3 % felt more secure when masticating on teeth and 7.7 % when masticating on implants ( mean VAS : 54+/-24 ) . The vast majority ( 96 % , mean VAS : 96+/-10 ) was highly satisfied or satisfied with phonetic function and with aesthetics ( 97 % , mean VAS : 93+/-13 ) . A great majority of the patients ( 93 % , mean VAS : 89+/-19 ) had no problems with cleansing the implant reconstruction . Indeed , one-third ( 37 % , mean VAS : 55+/-27 ) indicated more ease to clean implants than to clean teeth . About half of the patients ( 47 % ) had noticed bleeding of the mucosa or the gingiva following brushing . In addition , half ( 47 % ) of those noticing bleeding felt that bleeding was less marked around implants than around teeth . Again , the vast majority of patients ( 92 % , mean VAS : 92+/-14 ) indicated complete fulfilment of the treatment , i.e. the outcome satisfied their expectations . The same majority ( 94 % , mean VAS : 93+/-17 ) would be willing to undergo the same treatment again , and ( 89 % , mean VAS : 93+/-16 ) would even recommend such treatment to friends and relatives , if indicated . The cost for implant therapy was deemed to be reasonable to a large extent ( 87 % , mean VAS : 85+/-20 ) . CONCLUSION Using oral implants , more than 90 % of the patients were completely satisfied with implant therapy , both from a functional and aesthetic point of view . The costs associated with implant therapy were considered to be justified . This was determined by both qualified questions and the use of VAS after 10 years of function OBJECTIVE The aim of this study was to compare ball and magnet attachments within implant-supported m and ibular overdentures ( ISMOD ) using patient centred outcome measures . Our a priori hypothesis was that there is no difference in patient satisfaction between the two attachment types . MATERIAL AND METHODS In this within-subject crossover r and omised clinical trial , edentulous patients were recruited to the study and completed a denture satisfaction question naire before having two implants placed in the intraforaminal region of the m and ible . They were r and omly assigned to receive an ISMOD retained by either ball or magnetic attachment . After 3 months satisfaction question naires were repeated before attachments were changed to the alternative design . After a further 3 months patients completed final question naires . Patients were asked to choose their preferred prostheses and record the most influential factors in their final choice . The outcome variables of patient satisfaction were compared between baseline and the two attachment types using non-parametric two-related sample tests ( Wilcoxon 's signed rank ) . RESULTS AND DISCUSSION Sixteen patients completed the study . Patient satisfaction improved significantly between baseline and the new prosthesis with each attachment type for all domains of satisfaction ( P<0.05 ) . Ball attachments provided greater satisfaction in the domains of general satisfaction , stability and ability to chew ( P<0.05 ) . Patients ' general satisfaction with ball attachment retained overdentures was greater than that for magnetic attachments ; however , both design s provide significantly greater satisfaction than conventional dentures . In this study , the majority preferred to retain the ball attachment although one-third of patients actively chose the magnetic attachment PURPOSE To evaluate whether 6 mm-long by 4 mm-wide dental implants could be an alternative to at least 10 mm-long implants placed in bone augmented with bone substitutes in posterior atrophic jaws . MATERIAL S AND METHODS Twenty patients with bilateral atrophic m and ibles and 20 patients with bilateral atrophic maxillae , having 5 to 7 mm of bone height above the m and ibular canal or below the maxillary sinus , were r and omised according to a split-mouth design to receive one to three 6 mm-long and 4 mm-wide implants or at least 10-mm long implants in augmented bone at two centres . M and ibles were vertically augmented with interpositional equine bone blocks and resorbable barriers , and implants were placed after 3 months . Maxillary sinuses were augmented with particulated porcine bone via a lateral window and implants were placed simultaneously . All implants were submerged and loaded , after 4 months , with provisional prostheses . Four months later , definitive screw-retained metal-ceramic prostheses were delivered . Outcome measures were prosthesis and implant failures , any complication , time needed to fully recover mental nerve function ( only for m and ibular implants ) and patient preference . RESULTS All screened patients had sufficient bone width to support 4 mm-diameter implants . Patients were followed up to 5 months post-loading and none dropped out . There were no statistically significant differences in graft , implant or prosthesis failures , though significantly more intra- and postoperative complications occurred at grafted sites . Fourteen complications occurred in 12 patients at augmented sites versus none at short implants . All complications occurred before loading . Three complications were associated with the failure of the m and ibular grafts ( 15 % ) , determining the failures of 3 implants in one patient and 2 prostheses could not be delivered . One patient was re-grafted and 2 patients received short implants instead . Apart from those complications associated with graft failures , there were 4 perforations of the sinus membrane during sinus lifting and 7 temporary lower lip paraesthesiae lasting up to 4 days with no long-term consequences for the patients . All maxillary implants and prostheses were successful . All 20 patients treated with m and ibular implants and 15 patients treated with maxillary implants preferred short implants , whereas 5 patients treated with maxillary implants described both procedures as equally acceptable . These differences were statistically significant . CONCLUSIONS Short-term data ( 5 months after loading ) indicate that 6 mm-long implants with a conventional diameter of 4 mm achieved similar if not better results than longer implants placed in augmented bone . Short implants might be a preferable choice to bone augmentation , especially in posterior m and ibles since the treatment is faster , cheaper and associated with less morbidity . However , 5- to 10-year post-loading data are necessary before making reliable recommendations Evidence from r and omized clinical trials of implant-retained overdentures is very limited at the present time . The aim of this study was to compare implant-retained m and ibular overdentures and conventional complete dentures in a r and omized controlled trial ( RCT ) . Our a priori hypothesis was that implant-retained m and ibular overdentures would be significantly better than conventional complete dentures . Edentulous patients ( n = 118 ) were r and omly allocated to either an Implant Group ( n = 62 ) or a Denture Group ( n = 56 ) . Patients completed the Oral Health Impact Profile ( OHIP ) and a denture satisfaction scale pre-treatment and three months post-treatment . Upon completion of treatment , both groups reported improvement ( p < 0.001 , Wilcoxon Ranks Sum test ) in oral-health-related quality of life and denture satisfaction . There were no significant post-treatment differences between the groups , but a treatment effect may be masked by application of “ intention to treat ” analysis . The OHIP change scores were significantly greater for patients receiving implants than for those who refused them PURPOSE The goal of this multicenter prospect i ve clinical trial was to compare clinical outcome and post-treatment care and patient satisfaction with different implant systems used for m and ibular overdenture treatment during a 6-year follow-up period . PATIENTS AND METHODS A total of 87 edentulous patients with a severely resorbed m and ible ( bone height , 8 to 15 mm ) received treatment involving either 2 Intra Mobiele Zylinder implants ( IMZ group , n = 41 ) ( Friedrichsfeld AG , Mannheim , Germany ) , 2 Brånemark implants ( Brå group , n = 17 ) ( Nobel Biocare AB , Gothenburg , Sweden ) or a Transm and ibular Implant ( TMI ; Krijnen Medical , Beesd , The Netherl and s ) ( TMI group , n = 29 ) . The evaluation involved clinical parameters , radiographs , surgical and prosthetic post-treatment care , clinical implant performance ( CIP scale ) , and patient satisfaction . RESULTS After 6 years , there was a significant difference in the mean plaque index : the mean plaque index of the TMI group was significantly higher than that of the IMZ and Brå groups . Other clinical parameters showed no significant differences . The implant survival rate of 97.5 % was noted in the IMZ group , 97.1 % in the Brå group , and 72.0 % in the TMI group . The CIP scale were significantly worse for the TMI group . CONCLUSION It was concluded that the IMZ and the Brånemark implant systems have a better survival rate and clinical implant performance than the TMI system . Based on these data , these systems should be the choice for the edentulous m and ible with a height between 8 and 15 mm Although maxillary implant overdentures are used in oral rehabilitation , different design s have not been compared previously in clinical trials . This crossover trial was design ed to measure differences in patient satisfaction with maxillary long-bar implant overdentures with and without palatal coverage opposed by a fixed m and ibular implant-supported prosthesis . Data were also gathered on new conventional dentures and on maxillary conventional dentures opposed by m and ibular fixed prostheses . Sixteen participants were selected from a population wearing conventional dentures . Fifteen received new upper and lower dentures ( 1 drop-out ) . Four implants were placed in the maxilla and m and ible ( 2 drop-outs ) . A m and ibular fixed prosthesis was inserted in 13 participants , who were then divided into 2 groups . One group ( n = 7 ) received long-bar overdentures with palate , then long-bar overdentures without palate . The other group ( n = 6 ) received the same treatments in the reverse order . Mastication tests and psychometric evaluations using Visual Analog Scales and Categorical Scales were performed throughout the study . General satisfaction was very high with both maxillary implant-supported prostheses , as were ratings of almost all psychosocial and functional variables . There were no significant differences between treatments , suggesting that patients are equally satisfied with long-bar overdentures with and without palate when these are opposed by m and ibular fixed prostheses . However , the ratings given to the maxillary implant prostheses were not significantly higher than for new conventional maxillary prostheses . This suggests that maxillary implant prostheses should not be considered as a general treatment of choice in patients with good bony support for maxillary conventional prostheses PURPOSE This r and omized clinical trial examined implant overdenture ( IOD ) fabrication and maintenance time and costs , adjustment and repair incidence , and patient satisfaction after 1 year . MATERIAL S AND METHODS Sixty-four patients received 2 m and ibular implants and an IOD with either a bar with 2 clips or 2 ball attachments for denture retention . RESULTS Fabrication time , number of appointments , and chair time for adjustments were similar for the 2 denture design s. The most common adjustments for both types were to the IOD contours . Ball-attachment dentures required about 8 times longer for repairs than bar-clip prostheses . Approximately 84 % of patients with ball-attachment dentures needed at least 1 repair , versus 20 % of those with a bar-clip mechanism . The most common repairs were replacement of the cap spring or cap for the ball-attachment IOD and replacement of a lost or loose clip for bar-clip dentures . DISCUSSION Patients were equally and highly satisfied with the improvements in function , comfort , and appearance with both types of IOD compared to their original conventional dentures . CONCLUSIONS Given equivalent levels of patient satisfaction with either method of retention and a much higher repair rate for the ball attachment , it is suggested that a bar-clip design be used rather than the particular ball attachment utilized in this study OBJECTIVES Recent investigations have focused on patients ' subjective assessment of implant treatment . The aim of this study was to compare the patients ' experience of surgical and prosthetic procedures , as well as satisfaction with function and aesthetics following single-tooth replacements mounted to early vs. delayed placed dental implants . MATERIAL AND METHODS Forty-six patients were treated with a single-tooth implant in the anterior or premolar region . Twenty-three implants were placed on average 10 days after tooth extraction ( I m ) , while 23 implants were placed approximately 3 months after tooth extraction ( De ) . Forty-one patients completed a question naire regarding the treatment using visual analog scales ( VAS ) and check boxes 16 - 18 months after delivery of the restoration . RESULTS In all , 90 % of the respondents rated 88 or higher on the VAS regarding satisfaction with the crown . Satisfaction with the restoration in general and the appearance was significantly greater in the I m group than in the De group ( 96 vs. 93 ; P<0.02 ) . Assessment of the implant surgery was not significantly different between the delayed-immediate and the delayed group . Approximately 25 % of the patients experienced unpleasantness in relation to the prosthetic procedures , and in 8 of 11 cases , impression taking was the cause . When evaluating satisfaction with the overall implant treatment , the VAS scores for the delayed-immediate group were significantly higher than for the delayed group ( 96 vs. 90 ; P<0.02 ) . CONCLUSION The patients in the present study were highly satisfied with the outcome of the treatment and experienced it to be without significant unpleasantness irrespective of the treatment concept BACKGROUND There is evidence for the superiority of two-implant overdentures over complete dentures in the m and ible . Various anchorage devices were used to provide stability to overdentures . The aim of the present study was to compare two design s of a rigid bar connecting two m and ibular implants . MATERIAL S AND METHODS Completely edentulous patients received a new denture in the maxilla and an implant-supported overdenture in the m and ible . They were r and omly allocated to two groups ( A or B ) with regard to the bar design . A st and ard U-shaped bar ( Dolder bar ) was used connecting the two implants in a straight line . For comparison , precision attachments were soldered distal to the bar copings . Group A started the study with the st and ard bar ( S-bar ) , while group B started with the attachment-bar ( A-bar ) . After 3 months , they had to answer a question naire ( visual analogue scale [ VAS ] ) ; then the bar design was changed in both groups . After a period of another 3 months , the patients had to answer the same questions ; then they had the choice to keep their preferred bar . Now the study period was extended to another year of observation , and the patients answered again the same question naire . In vivo force measurements were carried out with both bar types at the end of the test periods . The prosthetic maintenance service carried out during the 6-month period was recorded for both bar types in both groups . Statistical analysis as performed with the SPSS statistical package ( SPSS Inc. , Chicago , IL , USA ) . RESULTS Satisfaction was high in both groups . Group B , who had entered the study with the attachment bar , gave slightly better ratings to this type for four items , while in group A , no differences were found . At the end of the 6-month comparison period , all but one patient wished to continue to wear the attachment bar . Prosthetic service was equal in groups A and B , but the total number of interventions is significantly higher in the attachment bar . Force patterns of maximum biting were similar in both bar design s , but exhibited significantly higher axial forces in the attachment bar . CONCLUSIONS Both bar design s provide good retention and functional comfort . High stability appears to be an important factor for the patients ' satisfaction and oral comfort . Rigid retention results in a higher force impact and appears to evoke the need for the retightening of occlusal screws , result ing in more maintenance service In a crossover experimental design , a prospect i ve clinical study was performed with 17 subjects with existing complete dentures . After data collection , two implants were placed bilaterally in the anterior m and ible . Conventional dentures were modified into implant overdentures by use of O-ring and magnet attachments . Each attachment was maintained with each subject for 6 months . Subjects responded to patient satisfaction and preference question naires about the conventional denture and each attachment . Subjects were satisfied with both attachment overdentures but showed a strong preference for the O-ring . Both attachments result ed in a significant increase in patient satisfaction when compared with the conventional denture |
10,353 | 19,344,379 | Although conclusive evidence is limited , the current data are indicative that a diet low in fat , high in vegetables and fruits , and avoiding high energy intake , excessive meat , excessive dairy products and calcium intake , is possibly effective in preventing PC .
The dietary recommendations for patients diagnosed with PC are similar to those aim ing to reduce their risk of PC | Dietary therapy has been proposed as a cost effective and noninvasive means of reducing the risk of prostate cancer ( PC ) and its progression .
There is a large volume of published studies describing the role of diet in the prevention and treatment of PC .
This article systematic ally review s the data for dietary-based therapy in the prevention of PC , as well as in the management of patients with PC , aim ing to provide clarity surrounding the role of diet in preventing and treating PC . | PURPOSE To determine whether a diet low in fat and high in fruits , vegetables , and fiber may be protective against prostate cancer by having an impact on serial levels of serum prostate-specific antigen ( PSA ) . METHODS Six hundred eighty-nine men were r and omized to the intervention arm and 661 to the control arm . The intervention group received intensive counseling to consume a diet low in fat and high in fiber , fruits , and vegetables . The control group received a st and ard brochure on a healthy diet . PSA in serum was measured at baseline and annually thereafter for 4 years , and newly diagnosed prostate cancers were recorded . RESULTS The individual PSA slope for each participant was calculated , and the distributions of slopes were compared between the two groups . There was no significant difference in distributions of the slopes ( P = .99 ) . The two groups were identical in the proportions of participants with elevated PSA at each time point . There was no difference in the PSA slopes between the two groups ( P = .34 ) and in the frequencies of elevated PSA values for those with elevated PSA at baseline . Incidence of prostate cancer during the 4 years was similar in the two groups ( 19 and 22 in the control and intervention arms , respectively ) . CONCLUSION Dietary intervention over a 4-year period with reduced fat and increased consumption of fruits , vegetables , and fiber has no impact on serum PSA levels in men . The study also offers no evidence that this dietary intervention over a 4-year period affects the incidence of prostate cancer during the 4 years The relationship between risk of prostate cancer and dietary intake of energy , fat , vitamin A , and other nutrients was investigated in a case-control study conducted in Ontario , Canada . Cases were men with a recent , histologically confirmed diagnosis of adenocarcinoma of the prostate notified to the Ontario Cancer Registry between April 1990 and April 1992 . Controls were selected r and omly from assessment lists maintained by the Ontario Ministry of Revenue , and were frequency-matched to the cases on age . The study included 207 cases ( 51.4 percent of those eligible ) and 207 controls ( 39.4 percent of those eligible ) , and information on dietary intake was collected from them by means of a quantitative diet history . There was a positive association between energy intake and risk of prostate cancer , such that men at the uppermost quartile level of energy intake had a 75 percent increase in risk . In contrast , there was no clear association between the non-energy effects of total fat and monounsaturated fat intake and prostate cancer risk . There was some evidence for an inverse association with saturated fat intake , although the dose-response pattern was irregular . There was a weak ( statistically nonsignificant ) positive association between polyunsaturated fat intake and risk of prostate cancer . Relatively high levels of retinol intake were associated with reduced risk , but there was essentially no association between dietary β-carotene intake and risk . There was no alteration in risk in association with dietary fiber , cholesterol , and vitamins C and E. Although these patterns were evident both overall and within age-strata , and persisted after adjustment for a number of potential confounding factors , they could reflect ( in particular ) the effect of nonrespondent bias A rising level of prostate-specific antigen ( PSA ) , after primary surgery or radiation therapy , is the hallmark of recurrent prostate cancer and is often the earliest sign of extraprostatic spread in patients who are otherwise asymptomatic . While hormonal therapy may slightly extend survival in a minority of patients , it is not curative and produces side effects including hot flashes , decreased libido , and loss of bone mass . Alternatively , dietary modification may offer an important tool for clinical management . Epidemiologic studies have associated the Western diet not only with prostate cancer incidence but also with a greater risk of disease progression after treatment . Conversely , many elements of plant-based diets have been associated with reduced risk of progression . However , dietary modification can be stressful and difficult to implement . We therefore conducted a 6-month pilot clinical trial to investigate whether adoption of a plant-based diet , reinforced by stress management training , could attenuate the rate of further PSA rise . Urologists at the University of California , San Diego , and San Diego Veterans Affairs Medical Centers recruited 14 patients with recurrent prostate cancer . A pre-post design was employed in which each patient served as his own control . Rates of PSA rise were ascertained for each patient for the following periods : from the time of posttreatment recurrence up to the start of the study ( pre study ) and from the time immediately preceding the intervention ( baseline ) to the end of the intervention ( 0 - 6 months ) . There was a significant decrease in the rate of PSA rise from pre study to 0 to 6 months ( P < .01 ) . Four of 10 evaluable patients experienced an absolute reduction in their PSA levels over the entire 6-month study . Nine of 10 had a reduction in their rates of PSA rise and an improvement of their PSA doubling times . Median PSA doubling time increased from 11.9 months ( pre study ) to 112.3 months ( intervention ) . These results provide preliminary evidence that adoption of a plant-based diet , in combination with stress reduction , may attenuate disease progression and have therapeutic potential for clinical management of recurrent prostate cancer Epidemiological studies have shown an inverse association between dietary intake of lycopene and prostate cancer risk . We conducted a clinical trial to investigate the biological and clinical effects of lycopene supplementation in patients with localized prostate cancer . Twenty-six men with newly diagnosed prostate cancer were r and omly assigned to receive a tomato oleoresin extract containing 30 mg of lycopene ( n = 15 ) or no supplementation ( n = 11 ) for 3 weeks before radical prostatectomy . Biomarkers of cell proliferation and apoptosis were assessed by Western blot analysis in benign and cancerous prostate tissues . Oxidative stress was assessed by measuring the Peripheral blood lymphocyte ONA oxidation product 5-hydroxymethyl-deoxyuridine ( 5-OH-mdU ) . Usual dietary Intake of nutrients was assessed by a food frequency question naire at baseline . Prostatectomy specimens were evaluated for pathologic stage , Gleason score , volume of cancer , and extent of high- grade prostatic intraepithelial neoplasia . Plasma levels of lycopene , insulin-like growth factor-1 , insulin-like growth factor binding protein-3 , and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation . After intervention , subjects in the intervention group had smaller tumors ( 80 % vs 45 % , less than 4 ml ) , less involvement of surgical margins and /or extra-prostatic tissues with cancer ( 73 % vs 18 % , organ-confined disease ) , and less diffuse involvement of the prostate by high- grade prostatic intraepithelial neoplasia ( 33 % vs 0 % , focal involvement ) compared with subjects in the control group . Mean plasma prostate-specific antigen levels were lower in the intervention group compared with the control group . This pilot study suggests that lycopene may have beneficial effects in prostate cancer . Larger clinical trials are Warranted to investigate the potential preventive and /or therapeutic role of lycopene in prostate cancer BACKGROUND Multivitamin supplements are used by millions of Americans because of their potential health benefits , but the relationship between multivitamin use and prostate cancer is unclear . METHODS We prospect ively investigated the association between multivitamin use and risk of prostate cancer ( localized , advanced , and fatal ) in 295,344 men enrolled in the National Institutes of Health (NIH)-AARP Diet and Health Study who were cancer free at enrollment in 1995 and 1996 . During 5 years of follow-up , 10,241 participants were diagnosed with incident prostate cancer , including 8765 localized and 1476 advanced cancers . In a separate mortality analysis with 6 years of follow-up , 179 cases of fatal prostate cancer were ascertained . Multivitamin use was assessed at baseline as part of a self-administered , mailed food-frequency question naire . Relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were calculated by use of Cox proportional hazards regression , adjusted for established or suspected prostate cancer risk factors . RESULTS No association was observed between multivitamin use and risk of localized prostate cancer . However , we found an increased risk of advanced and fatal prostate cancers ( RR = 1.32 , 95 % CI = 1.04 to 1.67 and RR = 1.98 , 95 % CI = 1.07 to 3.66 , respectively ) among men reporting excessive use of multivitamins ( more than seven times per week ) when compared with never users . The incidence rates per 100,000 person-years for advanced and fatal prostate cancers for those who took a multivitamin more than seven times per week were 143.8 and 18.9 , respectively , compared with 113.4 and 11.4 in never users . The positive associations with excessive multivitamin use were strongest in men with a family history of prostate cancer or who took individual micronutrient supplements , including selenium , beta-carotene , or zinc . CONCLUSION These results suggest that regular multivitamin use is not associated with the risk of early or localized prostate cancer . The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation PURPOSE The effects of a low-fat diet or a low-fat diet with the addition of a soy supplement were investigated in a pilot Phase II study for asymptomatic , hormonally naive prostate cancer patients with rising prostate-specific antigen ( PSA ) levels . EXPERIMENTAL DESIGN A two-step intervention was implemented . During step 1 patients were begun on a low-fat diet with a goal to reduce fat intake to 15 % of total daily calories . On PSA progression , a soy protein supplement was added to the diet ( step 2 ) . The primary end point was PSA reduction by 50 % . Secondary end points were PSA doubling time and time to progression ( TTP ) . Serum was analyzed for changes in the sex hormone and insulin-like growth factor ( IGF-I ) axes . RESULTS Among 18 evaluable patients , ( median follow-up on study 10.5 months ) , no patient on either step had a PSA reduction by 50 % at any time . There was a trend toward a longer PSA doubling time ( P = 0.06 ) and a prolongation in estimated median TTP of approximately 3 months ( P = 0.018 ) during step 2 compared with step 1 of the study . During step 1 , free testosterone levels decreased by 5 % ( P < 0.01 ) , and during step 2 , IGF-I levels increased by 22 % ( P = 0.02 ) . CONCLUSIONS A low-fat diet with the subsequent addition of a soy supplement did not result in a significant decline in PSA levels . The addition of soy protein had a modest effect on TTP . A potentially undesirable effect associated with the administration of soy was an increase in IGF-I serum levels The purpose of this study was to determine the effects of soy protein isolate consumption on circulating hormone profiles and hormone receptor expression patterns in men at high risk for developing advanced prostate cancer . Fifty-eight men were r and omly assigned to consume 1 of 3 protein isolates containing 40 g/d protein : 1 ) soy protein isolate ( SPI+ ) ( 107 mg/d isoflavones ) ; 2 ) alcohol-washed soy protein isolate ( SPI- ) ( < 6 mg/d isoflavones ) ; or 3 ) milk protein isolate ( 0 mg/d isoflavones ) . For 6 mo , the men consumed the protein isolates in divided doses twice daily as a partial meal replacement . Serum sample s collected at 0 , 3 , and 6 mo were analyzed for circulating estradiol , estrone , sex hormone-binding globulin , and rostenedione , and rostanediol glucuronide , dehydroepi and rosterone sulfate , dihydrotestosterone , testosterone , and free testosterone concentrations by RIA . Prostate biopsy sample s obtained pre- and postintervention were analyzed for and rogen receptor ( AR ) and estrogen receptor-beta expression by immunohistochemistry . At 6 mo , consumption of SPI+ significantly suppressed AR expression but did not alter estrogen receptor-beta expression or circulating hormones . Consumption of SPI- significantly increased estradiol and and rostenedione concentrations , and tended to suppress AR expression ( P = 0.09 ) . Although the effects of SPI- consumption on estradiol and and rostenedione are difficult to interpret and the clinical relevance is uncertain , these data show that AR expression in the prostate is suppressed by soy protein isolate consumption , which may be beneficial in preventing prostate cancer OBJECTIVES Epidemiological studies have shown significant relationships between the use of dietary components and prostate cancer incidence and mortality . Large studies of primary prevention , which confirm these findings , are desirable but costly and difficult to design . The present tertiary prevention study reports on the effect of a dietary supplement in comparison with placebo on the rate of increase of prostate-specific antigen ( PSA ) . METHODS 49 patients with a history of prostate cancer and rising PSA levels after radical prostatectomy ( n = 34 ) or radiotherapy ( n = 15 ) participated in a r and omised , double-blind , placebo-controlled crossover study of a dietary supplement . Ethical approval of the protocol was obtained . Treatment periods of 10 weeks were separated by a 4-week washout period . The supplement consisted of soy , isoflavones , lycopene , silymarin and antioxidants as main ingredients . Changes in the rate of increase of PSA ( PSA slope and doubling time ) were the primary parameters of efficacy . Analyses according to intention to treat ( ITT ) and per protocol ( PP ) were carried out . RESULTS Baseline parameters did not differ between r and omised groups . Five participants were lost to follow-up , however 46 could be evaluated in an ITT analysis . PP analysis could be performed in 42 men with at least 5 PSA measurements . Per protocol analysis showed a significant decrease in PSA slope ( p = 0.030 ) and (2)log PSA slope ( p = 0.041 ) . This translates into a 2.6 fold increase in the PSA doubling time from 445 to 1150 days for the supplement and placebo periods . No treatment-based changes in safety parameters were observed during the study . CONCLUSIONS The soy-based dietary supplement utilised in this study was shown to delay PSA progression after potentially curative treatment in a significant fashion . More extensive studies of the supplement may be indicated BACKGROUND The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the effect of daily beta-carotene ( 30 mg ) and retinyl palmitate ( 25,000 IU ) on the incidence of lung cancer , other cancers , and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure . CARET was stopped ahead of schedule in January 1996 because participants who were r and omly assigned to receive the active intervention were found to have a 28 % increase in incidence of lung cancer , a 17 % increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group . METHODS After the intervention ended , CARET participants returned the study vitamins to their study center and provided a final blood sample . They continue to be followed annually by telephone and mail self-report . Self-reported cancer endpoints were confirmed by review of pathology reports , and death endpoints were confirmed by review of death certificates . All statistical tests were two-sided . RESULTS With follow-up through December 31 , 2001 , the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 ( 95 % confidence interval [ CI ] = 0.97 to 1.31 ) and 1.08 ( 95 % CI = 0.99 to 1.17 ) , respectively . Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up . By contrast , the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped . During the post-intervention phase , females had larger relative risks of lung cancer mortality ( 1.33 versus 1.14 ; P = .36 ) , cardiovascular disease mortality ( 1.44 versus 0.93 ; P = .03 ) , and all-cause mortality ( 1.37 versus 0.98 ; P = .001 ) than males . CONCLUSIONS The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant . Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females , and cardiovascular disease mortality primarily to females and to former smokers OBJECTIVES To determine whether supplemental amounts of soy isoflavone ( genistein-rich extract ) would lower prostate-specific antigen ( PSA ) levels more than 50 % in patients with prostate cancer ( CaP ) . METHODS A total of 62 men ( mean age 73.6 years , range 61.4 to 89.3 ) with histologically proven CaP who had two consecutive elevated PSA readings were accrued during a 13-month period . An open-label pilot study was conducted for 6 months in which the patients took capsules containing the genistein-rich extract three times daily by mouth . The subjects were in one of five groups : after radical retropubic prostatectomy ( n = 9 ) , after radiotherapy ( n = 17 ) , after both radical retropubic prostatectomy and radiotherapy ( n = 6 ) , off-cycle during hormonal therapy ( intermittent hormones ; n = 14 ) , or active surveillance ( n = 16 ) . The primary endpoint for the trial was a 50 % reduction in the PSA level at 6 months compared with before treatment . RESULTS Of the 62 men enrolled , 52 were available for evaluation at 6 months . Three patients discontinued because of adverse events ( diarrhea ) and seven because of personal choice . One of 52 patients had a more than 50 % reduction in the PSA level ( 1.9 % response , 95 % confidence interval 0.1 % to 10.3 % ) . An additional 7 patients had PSA reductions that were less than 50 % . All 8 patients with lower PSA levels at 6 months were in the active surveillance ( watchful waiting ) treatment subgroup . Repeated measure regression models allowing for correlation between initial levels and change also indicated a decline in PSA in this group compared with other groups : 0 of 52 had a complete response , 9 ( 17 % ) had a partial response , 8 ( 15 % ) had stable disease , and 35 ( 67 % ) had disease progression . In the 9 patients with a partial response , 6 had pathologic findings that were moderately differentiated , 2 had well-differentiated findings , and 1 had poorly differentiated findings . Therefore , the response in this group of patients did not appear to be driven by the Gleason score . The total testosterone level was lowered in one of the patients responding , but it was higher in five others . CONCLUSIONS A genistein-rich extract as the sole treatment for CaP did not reduce PSA levels by 50 % or more in 51 of 52 subjects . Thus , it does not appear to be an effective treatment for CaP when given alone . However , 8 of 13 evaluated patients in the active surveillance group had either no rise or a decline in PSA levels of less than 50 % . More study is warranted for those choosing active surveillance PURPOSE Men with prostate cancer are often advised to make changes in diet and lifestyle , although the impact of these changes has not been well documented . Therefore , we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen ( PSA ) , treatment trends and serum stimulated LNCaP cell growth in men with early , biopsy proven prostate cancer after 1 year . MATERIAL S AND METHODS Patient recruitment was limited to men who had chosen not to undergo any conventional treatment , which provided an unusual opportunity to have a nonintervention r and omized control group to avoid the confounding effects of interventions such as radiation , surgery or and rogen deprivation therapy . A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were r and omly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group . RESULTS None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and /or progression of disease on magnetic resonance imaging . PSA decreased 4 % in the experimental group but increased 6 % in the control group ( p = 0.016 ) . The growth of LNCaP prostate cancer cells ( American Type Culture Collection , Manassas , Virginia ) was inhibited almost 8 times more by serum from the experimental than from the control group ( 70 % vs 9 % , p < 0.001 ) . Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle . CONCLUSIONS Intensive lifestyle changes may affect the progression of early , low grade prostate cancer in men . Further studies and longer term followup are warranted The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( n = 29,133 ) . During up to 9 years of follow-up , 317 men developed incident prostate cancer . Multivariate Cox proportional hazards models that adjusted for intervention group , benign prostatic hyperplasia , age , smoking , and urban residence were used to evaluate associations between prostate cancer and exposures of interest . There were no significant associations between baseline serum alpha-tocopherol , dietary vitamin E , or selenium and prostate cancer overall . The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status , with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention ( relative risk was 1.00 , 0.68 , 0.80 , and 0.52 for increasing quartiles ; P = 0.07 ) OBJECTIVES Dietary fat and fiber affect hormonal levels and may influence cancer progression . Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer . The potential effects of flaxseed may be enhanced with concomitant fat restriction . We undertook a pilot study to explore whether a flaxseed-supplemented , fat-restricted diet could affect the biomarkers of prostatic neoplasia . METHODS Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat ( 20 % of kilocalories or less ) , flaxseed-supplemented ( 30 g/day ) diet . The baseline and follow-up levels of prostate-specific antigen , testosterone , free and rogen index , and total serum cholesterol were determined . The tumors of diet-treated patients were compared with those of historic cases ( matched by age , race , prostate-specific antigen level at diagnosis , and biopsy Gleason sum ) with respect to apoptosis ( terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [ TUNEL ] ) and proliferation ( MIB-1 ) . RESULTS The average duration on the diet was 34 days ( range 21 to 77 ) , during which time significant decreases were observed in total serum cholesterol ( 201 + /- 39 mg/dL to 174 + /- 42 mg/dL ) , total testosterone ( 422 + /- 122 ng/dL to 360 + /- 128 ng/dL ) , and free and rogen index ( 36.3 % + /- 18.9 % to 29.3 % + /- 16.8 % ) ( all P < 0.05 ) . The baseline and follow-up levels of prostate-specific antigen were 8.1 + /- 5.2 ng/mL and 8.5 + /- 7.7 ng/mL , respectively , for the entire sample ( P = 0.58 ) ; however , among men with Gleason sums of 6 or less ( n = 19 ) , the PSA values were 7.1 + /- 3.9 ng/mL and 6.4 + /- 4.1 ng/mL ( P = 0.10 ) . The mean proliferation index was 7.4 + /- 7.8 for the historic controls versus 5.0 + /- 4.9 for the diet-treated patients ( P = 0.05 ) . The distribution of the apoptotic indexes differed significantly ( P = 0.01 ) between groups , with most historic controls exhibiting TUNEL categorical scores of 0 ; diet-treated patients largely exhibited scores of 1 . Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet ( P = 0.049 and P = 0.017 , respectively ) . CONCLUSIONS These pilot data suggest that a flaxseed-supplemented , fat-restricted diet may affect prostate cancer biology and associated biomarkers . Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy BACKGROUND Epidemiologic studies have suggested that vitamin E and beta-carotene may each influence the development of prostate cancer . In the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study , a controlled trial , we studied the effect of alpha-tocopherol ( a form of vitamin E ) and beta-carotene supplementation , separately or together , on prostate cancer in male smokers . METHODS A total of 29133 male smokers aged 50 - 69 years from southwestern Finl and were r and omly assigned to receive alpha-tocopherol ( 50 mg ) , beta-carotene ( 20 mg ) , both agents , or placebo daily for 5 - 8 years ( median , 6.1 years ) . The supplementation effects were estimated by a proportional hazards model , and two-sided P values were calculated . RESULTS We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period . A 32 % decrease ( 95 % confidence interval [ CI ] = -47 % to -12 % ) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol ( n = 14564 ) compared with those not receiving it ( n = 14569 ) . The reduction was evident in clinical prostate cancer but not in latent cancer . Mortality from prostate cancer was 41 % lower ( 95 % CI = -65 % to -1 % ) among men receiving alpha-tocopherol . Among subjects receiving beta-carotene ( n = 14560 ) , prostate cancer incidence was 23 % higher ( 95 % CI = -4%-59 % ) and mortality was 15 % higher ( 95 % CI = -30%-89 % ) compared with those not receiving it ( n = 14573 ) . Neither agent had any effect on the time interval between diagnosis and death . CONCLUSIONS Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers . Other controlled trials are required to confirm the findings A clinical trial of vitamin E and beta-carotene supplementation for lung cancer prevention among male smokers in Finl and recently reported an unexpected , strong protective effect of vitamin E against prostate cancer incidence and mortality . Our objective was to prospect ively examine supplemental vitamin E intake and prostate cancer risk in a distinct U.S. population . In 1986 , we identified 47,780 U.S. male health professionals , free from diagnosed cancer , who completed a dietary and lifestyle question naire ; supplemental vitamin E and prostate cancer incidence were up date d biennially through 1996 . We estimated relative risks ( RRs ) from multivariate pooled logistic regression models . There were 1896 total ( non-stage A1 ) , 522 extraprostatic , and 232 metastatic or fatal incident prostate cancer cases diagnosed between 1986 - 1996 . Men consuming at least 100 IU of supplemental vitamin E daily had multivariate RRs of 1.07 ( 95 % confidence interval [ CI ] , 0.95 - 1.20 ) for total and 1.14 ( 95 % CI , 0.82 - 1.59 ) for metastatic or fatal prostate cancer compared with those consuming none . Current use , dosage , and total duration of use of specific vitamin E supplements or multivitamins were not associated with risk . However , among current smokers and recent quitters , those who consumed at least 100 IU of supplemental vitamin E per day had a RR of 0.44 ( 95 % CI , 0.18 - 1.07 ) for metastatic or fatal prostate cancer compared with nonusers . Thus , supplemental vitamin E was not associated with prostate cancer risk generally , but a suggestive inverse association between supplemental vitamin E and risk of metastatic or fatal prostate cancer among current smokers and recent quitters was consistent with the Finnish trial among smokers and warrants further investigation The Physicians ' Health Study was a r and omized , double‐blind , placebo‐controlled trial using a 2 × 2 factorial design including supplementation with β‐carotene ( 50 mg every other day ) in the primary prevention of cancer among 22,071 U.S. male physicians ages 40–84 years at r and omization . Before r and omization , the authors collected baseline blood specimens to determine whether any benefit was greater among or confined to those with low baseline levels of β‐carotene High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk , but available prospect i ve data regarding these associations are inconsistent . We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol , Beta-Carotene ( ATBC ) Cancer Prevention Study , a cohort of 29,133 male smokers aged 50 - 69 years at study entry . Dietary intake was assessed at baseline using a vali date d 276-item food use question naire . Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer . During 17 years of follow-up , we ascertained 1,267 incident cases of prostate cancer . High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk . The multivariate relative risk ( RR ) of prostate cancer for > or = 2,000 mg/day compared to < 1,000 mg/day of calcium intake was 1.63 ( 95 % confidence interval ( CI ) , 1.27 - 2.10 ; p trend < 0.0001 ) . Total dairy intake was also positively associated with risk of prostate cancer . The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 ( 95 % CI , 1.04 - 1.51 ; p trend = 0.03 ) . However , no association with total dairy intake remained after we adjusted for calcium ( p trend = 0.17 ) . Findings were similar by stage and grade of prostate cancer . The results from this large prospect i ve study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk Background : In some studies , high calcium intake has been associated with an increased risk of prostate cancer , but no r and omized studies have investigated this issue . Methods : We r and omly assigned 672 men to receive either 3 g of calcium carbonate ( 1,200 mg of calcium ) , or placebo , daily for 4 years in a colorectal adenoma chemoprevention trial . Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses . Subject reports were verified by medical record review . Serum sample s , collected at r and omization and after 4 years , were analyzed for 1,25-(OH)2 vitamin D , 25-(OH ) vitamin D , and prostate-specific antigen ( PSA ) . We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels . Results : After a mean follow-up of 10.3 years , there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [ unadjusted rate ratio , 0.83 ; 95 % confidence interval ( 95 % CI ) , 0.52 - 1.32 ] . Most cases were not advanced ; the mean Gleason 's score was 6.2 . During the first 6 years ( until 2 years post-treatment ) , there were significantly fewer cases in the calcium group ( unadjusted rate ratio , 0.52 ; 95 % CI , 0.28 - 0.98 ) . The calcium risk ratio for conversion to PSA > 4.0 ng/mL was 0.63 ( 95 % CI , 0.33 - 1.21 ) . Baseline dietary calcium intake , plasma 1,25-(OH)2 vitamin D and 25-(OH ) vitamin D levels were not material ly associated with risk . Conclusion : In this r and omized controlled clinical trial , there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect Background : Reports from several studies have suggested that carotenoids , and in particular lycopene , could be prostate cancer – preventive agents . This has stimulated extensive laboratory and clinical research , as well as much commercial and public enthusiasm . However , the epidemiologic evidence remains inconclusive . Material s and Methods : We investigated the association between prediagnostic serum carotenoids ( lycopene , α-carotene , β-carotene , β-cryptoxanthin , lutein , and zeaxanthin ) and risk of prostate cancer in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial , a multicenter study design ed to examine methods of early detection and risk factors for cancer . The study included 692 incident prostate cancer cases , diagnosed 1 to 8 years after study entry , including 270 aggressive cases , with regional or distant stage ( n = 90 ) or Gleason score ≥7 ( n = 235 ) , and 844 r and omly selected , matched controls . As study participants were selected from those who were assigned to annual st and ardized screening for prostate cancer , results are unlikely to be biased by differential screening , a circumstance that is difficult to attain under non – trial conditions . Results : No association was observed between serum lycopene and total prostate cancer [ odds ratios ( OR ) , 1.14 ; 95 % confidence intervals ( 95 % CI ) , 0.82 - 1.58 for highest versus lowest quintile ; P for trend , 0.28 ] or aggressive prostate cancer ( OR , 0.99 ; 95 % CI , 0.62 - 1.57 for highest versus lowest quintile ; P for trend , 0.433 ) . β-Carotene was associated with an increased risk of aggressive prostate cancer ( OR , 1.67 ; 95 % CI , 1.03 - 2.72 for highest versus lowest quintile ; P for trend , 0.13 ) ; in particular , regional or distant stage disease ( OR , 3.16 ; 95 % CI , 1.37 - 7.31 for highest versus lowest quintile ; P for trend , 0.02 ) ; other carotenoids were not associated with risk . Conclusion : In this large prospect i ve study , high serum β-carotene concentrations were associated with increased risk for aggressive , clinical ly relevant prostate cancer . Lycopene and other carotenoids were unrelated to prostate cancer . Consistent with other recent publications , these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention . ( Cancer Epidemiol Biomarkers Prev 2007;16(5):962–8 The incidence of prostate cancer is much lower in Asian than Western population s. Given that environmental factors such as dietary habits may play a major role in the causation of prostate cancer and the high consumption of green tea in Asian population s , this low incidence may be partly due to the effects of green tea . The JPHC Study ( Japan Public Health Center-based Prospect i ve Study ) was established in 1990 for cohort I and in 1993 for cohort II . The subjects were 49,920 men aged 40 - 69 years who completed a question naire that included their green tea consumption habit at baseline and were followed until the end of 2004 . During this time , 404 men were newly diagnosed with prostate cancer , of whom 114 had advanced cases , 271 were localized , and 19 were of an undetermined stage . Green tea was not associated with localized prostate cancer . However , consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer . The multivariate relative risk was 0.52 ( 95 % confidence interval : 0.28 , 0.96 ) for men drinking 5 or more cups/day compared with less than 1 cup/day ( p(trend ) = 0.01 ) . Green tea may be associated with a decreased risk of advanced prostate cancer Supplemental vitamin E ( α-tocopherol ) has been linked to lower prostate cancer incidence in one r and omized trial and several , although not all , observational studies . The evidence regarding dietary intake of individual vitamin E isoforms and prostate cancer is limited and inconclusive , however . We prospect ively examined the relations of supplemental vitamin E and dietary intakes of α- , β- , γ- , and δ- tocopherols to prostate cancer risk among 295,344 men , ages 50 to 71 years and cancer-free at enrollment in 1995 to 1996 , in the NIH-AARP Diet and Health Study . At baseline , participants completed a question naire that captured information on diet , supplement use , and other factors . Proportional hazards models were used to estimate relative risks ( RR ) and 95 % confidence intervals ( 95 % CI ) of prostate cancer . During 5 years of follow-up , 10,241 incident prostate cancers were identified . Supplemental vitamin E intake was not related to prostate cancer risk ( for > 0 - 99 , 100 - 199 , 200 - 399 , 400 - 799 , and ≥800 IU/d versus never use : RR , 0.97 , 0.89 , 1.03 , 0.99 , and 0.97 ( 95 % CI , 0.87 - 1.07 ) respectively ; Ptrend = 0.90 ) . However , dietary γ-tocopherol , the most commonly consumed form of vitamin E in the United States , was significantly inversely related to the risk of advanced prostate cancer ( for highest versus lowest quintile : RR , 0.68 ; 95 % CI , 0.56 - 0.84 ; Ptrend = 0.001 ) . These results suggest that supplemental vitamin E does not protect against prostate cancer , but that increased consumption of γ-tocopherol from foods is associated with a reduced risk of clinical ly relevant disease . The potential benefit of γ-tocopherol for prostate cancer prevention deserves further attention . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1128–35 High-temperature cooked meat contains heterocyclic amines , including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP ) , and polycyclic aromatic hydrocarbons , such as benzo(a)pyrene ( BaP ) . In rodents , a high intake of PhIP induces prostate tumors . We prospect ively investigated the association between meat and meat mutagens , specifically PhIP , and prostate cancer risk in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . Diet was assessed using a 137-item food frequency question naire and a detailed meat-cooking question naire linked to a data base for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline ( MeIQx ) , 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline ( DiMeIQx ) , and PhIP . During follow-up , we ascertained a total of 1,338 prostate cancer cases among 29,361 men ; of these , 868 were incident cases ( diagnosed after the first year of follow-up ) and 520 were advanced cases ( stage III or IV or a Gleason score of > or = 7 ) . Total , red , or white meat intake was not associated with prostate cancer risk . More than 10 g/d of very well done meat , compared with no consumption , was associated with a 1.4-fold increased risk of prostate cancer [ 95 % confidence interval ( 95 % CI ) , 1.05 - 1.92 ] and a 1.7-fold increased risk ( 95 % CI , 1.19 - 2.40 ) of incident disease . Although there was no association with MeIQx and DiMeIQx , the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer ( 95 % CI , 1.01 - 1.48 ) and a 1.3-fold increased risk of incident disease ( 95 % CI , 1.01 - 1.61 ) . In conclusion , very well done meat was positively associated with prostate cancer risk . In addition , this study lends epidemiologic support to the animal studies , which have implicated PhIP as a prostate carcinogen BACKGROUND Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease , and earlier basic research suggested plausible mechanisms . Because large r and omized trials of long duration were necessary to test this hypothesis directly , we conducted a trial of beta carotene supplementation . METHODS In a r and omized , double-blind , placebo-controlled trial of beta carotene ( 50 mg on alternate days ) , we enrolled 22,071 male physicians , 40 to 84 years of age , in the United States ; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982 . By December 31 , 1995 , the scheduled end of the study , fewer than 1 percent had been lost to follow-up , and compliance was 78 percent in the group that received beta carotene . RESULTS Among 11,036 physicians r and omly assigned to receive beta carotene and 11,035 assigned to receive placebo , there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease , or in overall mortality . In the beta carotene group , 1273 men had any malignant neoplasm ( except nonmelanoma skin cancer ) , as compared with 1293 in the placebo group ( relative risk , 0.98 ; 95 percent confidence interval , 0.91 to 1.06 ) . There were also no significant differences in the number of cases of lung cancer ( 82 in the beta carotene group vs. 88 in the placebo group ) ; the number of deaths from cancer ( 386 vs. 380 ) , deaths from any cause ( 979 vs. 968 ) , or deaths from cardiovascular disease ( 338 vs. 313 ) ; the number of men with myocardial infa rct ion ( 468 vs. 489 ) ; the number with stroke ( 367 vs. 382 ) ; or the number with any one of the previous three end points ( 967 vs. 972 ) . Among current and former smokers , there were also no significant early or late differences in any of these end points . CONCLUSIONS In this trial among healthy men , 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms , cardiovascular disease , or death from all causes Epidemiological data on most cancer sites suggest that consumption of plant foods , which contain high levels of antioxidants , might slow or prevent the appearance of cancer . We used data from three case-control studies to test this hypothesis . The total study population consisted of 617 incident cases of prostate cancer and 636 population controls from Ontario , Quebec , and British Columbia . Dietary information was collected by an in-person interview with a detailed quantitative dietary history . Unconditional logistic regression analyses were performed to estimate odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . A decreasing , statistically significant association was found with increasing intakes of green vegetables ( OR = 0.54 , 95 % CI = 0.40 - 0.71 for 4th quartile ) , tomatoes ( OR = 0.64 , 95 % CI = 0.45 - 0.91 ) , beans/lentils/nuts ( OR = 0.69 , 95 % CI = 0.53 - 0.91 ) , and cruciferous vegetables ( OR = 0.69 , 95 % CI = 0.52 - 0.91 for 3rd quartile ) . Higher intakes of fruit were associated with higher ORs ( OR = 1.51 , 95 % CI = 1.14 - 2.01 for 4th quartile ) , an effect that was seen for total fruit and citrus fruit , as well as for all other noncitrus fruits . Among the grains , refined-grain bread intake was associated with a decrease in risk ( OR = 0.65 for 4th quartile ) , whereas whole-grain breakfast cereals were associated with a higher risk for prostate cancer . Of all the antioxidant nutrients studied , the ORs were higher with higher intakes of cryptoxanthin ( OR = 1.44 , 95 % CI = 1.09 - 1.89 for 4th quartile ) . Exposure to certain dietary components of plant origin , which are potentially modifiable , indicates the theoretical scope for reducing the risk from prostate cancer . Future experimental studies or trials are warranted for further underst and ing Objective To evaluate the association of meat and dairy food consumption with subsequent risk of prostate cancer . Methods In 1989 , 3,892 men 35 + years old , who participated in the CLUE II study of Washington County , MD , completed an abbreviated Block food frequency question naire . Intake of meat and dairy foods was calculated using consumption frequency and portion size . Incident prostate cancer cases ( n = 199 ) were ascertained through October 2004 . Cox proportional hazards regression was used to calculate hazard ratios ( HR ) of total and advanced ( SEER stages three and four ; n = 54 ) prostate cancer and 95 % confidence intervals ( CI ) adjusted for age , BMI at age 21 , and intake of energy , saturated fat , and tomato products . Results Intakes of total meat ( HR = 0.90 , 95 % CI 0.60–1.33 , comparing highest to lowest tertile ) and red meat ( HR = 0.87 , 95 % CI 0.59–1.32 ) were not statistically significantly associated with prostate cancer . However , processed meat consumption was associated with a non-statistically significant higher risk of total ( 5 + vs. ≤1 servings/week : HR = 1.53 , 95 % CI 0.98–2.39 ) and advanced ( HR = 2.24 ; 95 % CI 0.90–5.59 ) prostate cancer . There was no association across tertiles of dairy or calcium with total prostate cancer , although compared to ≤1 serving/week consumption of 5 + servings/week of dairy foods was associated with an increased risk of prostate cancer ( HR = 1.65 , 95 % CI 1.02–2.66 ) . Conclusion Overall , consumption of processed meat , but not total meat or red meat , was associated with a possible increased risk of total prostate cancer in this prospect i ve study . Higher intake of dairy foods but not calcium was positively associated with prostate cancer . Further investigation into the mechanisms by which processed meat and dairy consumption might increase the risk of prostate cancer is suggested To present the results ( to January 1996 , the end of blinded treatment ) of the Nutritional Prevention of Cancer ( NPC ) Trial , a r and omized trial of selenium ( 200 µg daily ) design ed to test the hypothesis that selenium supplementation ( SS ) could reduce the risk of recurrent nonmelanoma skin cancer among 1312 residents of the Eastern USA OBJECTIVE To assess the effect of a nutritional supplement containing vitamin E , selenium , vitamin C and coenzyme Q10 on changes in serum levels of PSA in patients with hormonally untreated carcinoma of the prostate and rising serum PSA levels . METHODS Eighty patients were r and omised to receive a daily supplement with either vitamin E , selenium , vitamin C , coenzyme Q10 ( intervention group ) or placebo over 21 weeks . Serum levels of PSA were assessed at baseline ( -2 , -1 , 0 weeks ) and after 6 , 13 , 19 , 20 and 21 weeks . Mean changes in log serum level of PSA , testosterone , dihydrotestosterone , luteinizing hormone and sex hormone binding globulin over 21 weeks between the verum and the placebo group were compared by analysis of covariance . RESULTS Seventy patients completed the study ( 36 verum ; 34 placebo ) . Compliance was > 90 % in all patients . In the intervention group , plasma levels of vitamin E , selenium and coenzyme Q10 increased significantly over the 21 weeks study period . No significant differences in serum levels of PSA , testosterone , dihydrotestosterone , luteinizing hormone or sex hormone binding globulin ( p>0.2 ) were observed between the intervention and control group . CONCLUSION Our results indicate that supplementation of a combination of vitamin E , selenium , vitamin C and coenzyme-Q10 does not affect serum level of PSA or hormone levels in patients with hormonally untreated carcinoma of the prostate Objective Vitamin E and selenium are promising nutrients for the prevention of prostate cancer , and both are currently being tested in a large r and omized trial for prostate cancer . However , results are not expected for at least 6 years . We aim ed to investigate the association of vitamin E and selenium supplementation with prostate cancer in the VITamins And Lifestyle ( VITAL ) study , a cohort study specifically design ed to examine supplement use and future cancer risk . Methods In a prospect i ve design , 35,242 men recruited between 2000 and 2002 from western Washington State completed a question naire , including detailed questions about vitamin E and selenium supplement intake during the past 10 years from br and -specific multivitamins and single supplements . Using linkage to the western Washington SEER cancer registry , we documented 830 new cases of prostate cancer from baseline through December 2004 . Results A 10-year average intake of supplemental vitamin E was not associated with a reduced prostate cancer risk overall [ hazard ratio ( HR ) 0.86 , 95 % confidence interval ( CI ) 0.65–1.1 for ≥400 IU/day vs. non-use , p for trend 0.36 ] ; however , risk for advanced prostate cancer ( regionally invasive or distant metastatic , n = 123 ) decreased significantly with greater intake of supplemental vitamin E ( HR 0.43 , 95 % CI 0.19–1.0 for 10-year average intake ≥400 IU/day vs. non-use , p for trend 0.03 ) . There was no association between selenium supplementation and prostate cancer risk ( HR 0.90 , 95 % CI 0.62–1.3 for 10-year average intake > 50 μg/day vs. non-use , p for trend 0.97 ) . Conclusions In this prospect i ve cohort , long-term supplemental intake of vitamin E and selenium were not associated with prostate cancer risk overall ; however , risk of clinical ly relevant advanced disease was reduced with greater long-term vitamin E supplementation OBJECTIVES To determine the effects of diets rich in soy and linseed compared with a control diet on biochemical markers of prostate cancer in men diagnosed with prostate cancer . METHODS Twenty-nine men diagnosed with prostate cancer and scheduled to undergo a radical prostatectomy were r and omized to one of three groups : soy ( high phytoestrogen ) , soy and linseed ( high phytoestrogen ) , or wheat ( low phytoestrogen ) . A bread was specially manufactured to incorporate 50 g of heat-treated ( HT ) soy grits or 50 g of HT soy grits and 20 g of linseed as part of the study participant 's daily diet . Baseline and preoperative levels of prostate-specific antigen ( PSA ) , free PSA , testosterone , sex hormone-binding globulin , free and rogen index , and dihydrotestosterone were measured . RESULTS Statistically significant differences were detected between the HT soy grits group and the control wheat group for the percentage of change in total PSA ( -12.7 % versus 40 % , P = 0.02 ) and the percentage of change in free/total PSA ratio ( 27.4 % versus -15.6 % , P = 0.01 ) ; and between the HT soy grits group and the HT soy grits and linseed group for the percentage of change in free and rogen index ( 16.4 % versus -15.5 % , P = 0.04 ) and the percentage of change in free/total PSA ratio ( 27.4 % versus -10 % , P = 0.007 ) . CONCLUSIONS The data from this study indicate that a daily diet containing four slices of a bread rich in HT soy grits favorably influences the PSA level and the free/total PSA ratio in patients with prostate cancer . This work provides some evidence to support epidemiologic studies cl aim ing that male population s who consume high phytoestrogen diets have a reduced risk of prostate cancer development and progression OBJECTIVES Dietary factors may influence the prostate and have an impact on prostatic growth and disease . A small number of studies have suggested that flaxseed-supplemented , fat-restricted diets may thwart prostate cancer growth in both animals and humans . Unknown , however , is the potential effect of such a diet on benign prostatic epithelium . METHODS We undertook a pilot study to explore whether a flaxseed-supplemented , fat-restricted diet affects the proliferation rates in benign epithelium . We also explored the effects on circulating levels of prostate-specific antigen ( PSA ) , total testosterone , and cholesterol . Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat ( less than 20 % kcal ) , flaxseed-supplemented ( 30 g/day ) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period . The PSA , total testosterone , and cholesterol levels were determined at baseline and at 6 months of follow-up . Reports from the original and repeat biopsies were compared , and proliferation ( MIB-1 ) rates were quantified in the benign prostatic epithelium . RESULTS Statistically significant decreases in PSA ( 8.47 + /- 3.82 to 5.72 + /- 3.16 ng/mL ; P = 0.0002 ) and cholesterol ( 241.1 + /- 30.8 to 213.3 + /- 51.2 mg/dL ; P = 0.012 ) were observed . No statistically significant change was seen in total testosterone ( 434.5 + /- 143.6 to 428.3 + /- 92.5 ng/dL ) . Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization , of the 13 men who underwent repeat biopsy , the proliferation rates in the benign epithelium decreased significantly from 0.022 + /- 0.027 at baseline to 0.007 + /- 0.014 at 6 months of follow-up ( P = 0.0168 ) . CONCLUSIONS These pilot data suggest that a flaxseed-supplemented , fat-restricted diet may affect the biology of the prostate and associated biomarkers . A r and omized controlled trial is needed to determine whether flaxseed supplementation , a low-fat diet , or a combination of the two regimens may be of use in controlling overall prostatic growth OBJECTIVE To test if supplemental dietary selenium is associated with changes in the incidence of prostate cancer . PATIENTS AND METHOD A total of 974 men with a history of either a basal cell or squamous cell carcinoma were r and omized to either a daily supplement of 200 microg of selenium or a placebo . Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years . RESULTS Selenium treatment was associated with a significant ( 63 % ) reduction in the secondary endpoint of prostate cancer incidence during 1983 - 93 . There were 13 prostate cancer cases in the selenium-treated group and 35 cases in the placebo group ( relative risk , RR=0.37 , P=0.002 ) . Restricting the analysis to the 843 patients with initially normal levels of prostate-specific antigen ( < or = 4 ng/mL ) , only four cases were diagnosed in the selenium-treated group and 16 cases were diagnosed in the placebo group after a 2 year treatment lag , ( RR=0.26 P=0.009 ) . There were significant health benefits also for the other secondary endpoints of total cancer mortality , and the incidence of total , lung and colorectal cancer . There was no significant change in incidence for the primary endpoints of basal and squamous cell carcinoma of the skin . In light of these results , the ' blinded ' phase of this trial was stopped early . CONCLUSIONS Although selenium shows no protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin , the selenium-treated group had substantial reductions in the incidence of prostate cancer , and total cancer incidence and mortality that dem and further evaluation in well-controlled prevention trials PURPOSE Epidemiological and laboratory evidence indicates that a Western diet is associated with an increased incidence of prostate cancer . Specific components of the diet , such as high saturated fat , low fiber and high meat content , may have greatest clinical significance in the later stages of tumor promotion and progression . However , departure from the conventional diet is difficult to initiate and maintain . Therefore , we combined the well-known Mindfulness-Based Stress Reduction ( MBSR ) program with a low saturated fat , high-fiber , plant-based diet to determine the effect on the rate of change in prostate specific antigen ( PSA ) in patients with biochemical recurrence after prostatectomy . MATERIAL S AND METHODS We enrolled 10 men and their partners in a 4-month group-based diet and MBSR intervention . A pre- study post- study design in which each subject served as his own control was used to compare the rate of increase in and doubling time of PSA before and after intervention . RESULTS The rate of PSA increase decreased in 8 of 10 men , while 3 had a decrease in absolute PSA . Results of the signed rank test indicated a significant decrease in the rate of increase in the intervention period ( p = 0.01 ) . Estimated median doubling time increased from 6.5 months ( 95 % confidence interval 3.7 to 10.1 ) before to 17.7 months ( 95 % confidence interval 7.8 to infinity ) after the intervention . CONCLUSIONS Our small study provides evidence that a plant-based diet delivered in the context of MBSR decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer . Larger-scale r and omized studies are warranted to explore further the preventive and therapeutic potential of diet and lifestyle modification in men with prostate cancer OBJECTIVES Tomatoes are rich in lycopene . This study explored the efficacy of a lycopene-rich tomato product in and rogen-independent prostate cancer and the reasons patients participated in an " alternative medicine " study . METHODS This Phase II study evaluated 46 patients with and rogen-independent prostate cancer . All were asymptomatic and had serum prostate-specific antigen elevation despite hormonal manipulation . All patients completed a question naire on their motivations for enrolling in an " alternative medicine " study . Patients were prescribed a lycopene-rich tomato supplement at a lycopene dose of 15 mg twice daily . RESULTS One patient manifested a tumor response with a 50 % or greater confirmed decline in serum prostate-specific antigen level , yielding a response rate of 2 % . Lycopene was well tolerated , but 1 patient died of a cancer-related hemorrhage , and 1 had grade 4 diarrhea . Grade 1 or 2 events included diarrhea in 18 , nausea in 12 , abdominal distension in 8 , flatulence in 2 , vomiting in 2 , anorexia in 1 , and dyspepsia in 1 . The reasons for entering the trial are discussed and were overall positive . CONCLUSIONS Lycopene , as prescribed in our study , did not appear effective for and rogen-independent prostate cancer . The patients ' reasons for enrolling in this trial were positive and realistic Objectives : Recent experimental studies have suggested that isoflavones ( such as genistein and daidzein ) found in some soy products may reduce the risk of cancer . The purpose of this study was to evaluate the relationship between soy milk , a beverage containing isoflavones , and prostate cancer incidence . Methods : A prospect i ve study with 225 incident cases of prostate cancer in 12,395 California Seventh-Day Adventist men who in 1976 stated how often they drank soy milk . Results : Frequent consumption ( more than once a day ) of soy milk was associated with 70 per cent reduction of the risk of prostate cancer ( relative risk=0.3 , 95 percent confidence interval 0.1 - 1.0 , p-value for linear trend=0.03 ) . The association was upheld when extensive adjustments were performed . Conclusions : Our study suggests that men with high consumption of soy milk are at reduced risk of prostate cancer . Possible associations between soy bean products , isoflavones and prostate cancer risk should be further investigated The objective of this study was to show or to exclude an effect of dietary supplement on rising prostate‐specific antigen ( PSA ) levels . We have studied the effect of a dietary supplement ( verum , administered for 6 weeks ) containing plant estrogens , antioxidants , including carotenoids , selenium and other putative prostate cancer inhibiting substances in a r and omized placebo‐controlled double‐blind crossover study in 37 hormonally untreated men with prostate cancer and increasing PSA levels . Outcome measures were changes in the rates of change of serum concentrations of total and free PSA and changes in male sex hormone levels . Male sex hormone levels were significantly lower during the verum phase ( DHT : −0.11 nmol/L , p = 0.005 ; testosterone : −1 nmol/L , p = 0.02 ) . Total PSA doubling time was unaffected . Free PSA , which increased during the placebo phase ( average doubling time of 68 weeks ) , decreased during the verum period ( average half‐life of 13 weeks ; p = 0.02 ) . In those men in whom the free and rogen index decreased ( 21 out of 32 ) , a significant decrease in the slopes of both total and free PSA was observed ( p = 0.04 ) . Overall total PSA doubling times did not increase significantly during verum . However , the study demonstrates that this dietary intervention reduces DHT and testosterone levels and increases free PSA doubling time ( and total PSA doubling time in a relevant subgroup ) . If future studies confirm that these observations translate into a slowing of disease progression , a dietary intervention may become an attractive option for prostate cancer treatment and prevention . © 2004 Wiley‐Liss , The Western diet has been associated with prostate cancer incidence as well as risk of disease progression after treatment . Conversely , plant-based diets have been associated with decreased risks . A pilot clinical trial of a 6-month dietary change and stress reduction intervention for asymptomatic , hormonally untreated patients experiencing a consistently rising PSA level , the first sign of recurrence of prostate cancer after surgery or radiation therapy , was conducted to investigate the level of intake of plant-based foods and the relationship between intake and the change in the rate of PSA rise . A pre-post design was employed in which each patient served as his own control . In this multifaceted intervention , patients and their spouses were encouraged to adopt and maintain a plant-based diet . The pre study rate of PSA rise ( from the time of posttreatment recurrence to the start of the study ) was ascertained by review of patients ’ medical records . Dietary assessment s were performed and prostate-specific antigen ( PSA ) levels ascertained at baseline , prior to the start of intervention , and at 3 and 6 months . Changes in numbers of servings of plant-based food groups were calculated and compared with rates of PSA rise over the corresponding time intervals . Median intake of whole grains increased from 1.7 servings/d at baseline to 6.9 and 5.0 servings/d at 3 and 6 months , respectively . Median intake of vegetables increased from 2.8 servings/d at baseline to 5.0 and 4.8 servings/d at 3 and 6 months , respectively . The rate of PSA rise decreased when comparing the pre study period ( 0.059 ) to the period from 0 to 3 months ( -0.002 , P < .01 ) and increased slightly , though not significantly , when comparing the period from 0 to 3 months to the period from 3 to 6 months ( 0.029 , P = .4316 ) . These results provide preliminary evidence that adoption of a plant-based diet is possible to achieve as well as to maintain for several months in patients with recurrent prostate cancer . Changes in the rate of rise in PSA , an indicator of disease progression , were in the opposite direction as changes in the intake of plant-based food groups , raising the provocative possibility that PSA may have inversely tracked intake of these foods and suggesting that adoption of a plant-based diet may have therapeutic potential in the management of this condition OBJECTIVES To investigate , through a prospect i ve follow-up study , the effects of a dietary supplementation challenge in men with isolated high- grade prostatic intraepithelial neoplasia ( HGPIN ) . METHODS The effects of a 6-month supplementation challenge with selenium , vitamin E , and soy isoflavonoids in men diagnosed with isolated HGPIN on biopsy were evaluated . A total of 100 patients entered the study . Of the 100 men , 29 were excluded because they refused additional biopsies or were noncompliant with the protocol , 71 underwent repeat biopsies at 3 months , and 58 underwent a third set at 6 months . The prostate-specific antigen ( PSA ) level was recorded at inclusion and before each set of biopsies . The study endpoint was defined as the diagnosis of PCa at 3 months or the histopathologic status at 6 months . RESULTS At the study endpoint , PCa had been found in 24 men ( 33.8 % ) , HGPIN in 34 ( 47.9 % ) , and no HGPIN or carcinoma in 13 ( 18.3 % ) . The PCa risk throughout the study period was 25.0 % in the group with a stable or decreasing PSA level ( n = 48 , 67.6 % ) and 52.2 % in the group with an increasing PSA level ( n = 23 , 32.4 % ) . This difference was statistically significant ( P = 0.0458 ) . Isolated HGPIN remaining at the first repeat biopsy and the percentage of initial cores with HGPIN were significant predictors of PCa at additional biopsies . CONCLUSIONS The results of our study have shown that a decrease in the PSA level while taking a selenium , vitamin E , and soy isoflavonoids supplement predicts for a significantly lower risk of PCa in future biopsies . The percentage of initial biopsy cores with HGPIN and isolated HGPIN remaining at the first repeat biopsy are significant predictors of PCa in future biopsies α-Tocopherol supplementation ( 50 mg daily for 5 - 8 years ) reduced prostate cancer incidence by 32 % in the α-Tocopherol , β-Carotene Cancer Prevention Study . We investigated whether serum α-tocopherol or intake of vitamin E ( eight tocopherols and tocotrienols ) was associated with prostate cancer risk with up to 19 years of follow-up in the α-Tocopherol , β-Carotene Cancer Prevention Study cohort . Of the 29,133 Finnish male smokers , ages 50 to 69 years recruited into the study , 1,732 were diagnosed with incident prostate cancer between 1985 and 2004 . Baseline serum α-tocopherol was measured by high-performance liquid chromatography and the components of vitamin E intake were estimated based on a 276-item food frequency question naire and food chemistry analyses . Proportional hazard models were used to determine multivariate-adjusted relative risks ( RR ) and 95 % confidence intervals ( 95 % CI ) . Higher serum α-tocopherol was associated with reduced risk of prostate cancer ( RR , 0.80 ; 95 % CI , 0.66 - 0.96 for highest versus lowest quintile ; Ptrend = 0.03 ) and was strongly and inversely related to the risk of developing advanced disease ( RR , 0.56 ; 95 % CI , 0.36 - 0.85 ; Ptrend = 0.002 ) . The inverse serum α-tocopherol-prostate cancer association was greater among those who were supplemented with either α-tocopherol or β-carotene during the trial . There were no associations between prostate cancer and the individual dietary tocopherols and tocotrienols . In summary , higher prediagnostic serum concentrations of α-tocopherol , but not dietary vitamin E , was associated with lower risk of developing prostate cancer , particularly advanced prostate cancer . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1253–9 OBJECTIVES The results of epidemiologic and animal studies support the role of a low-fat diet supplemented with omega-3 fatty acids contained in fish oil in preventing the development and progression of prostate cancer . As a first step in study ing the role of a low-fat , fish oil-supplemented ( LF/FOS ) diet in a clinical setting , we conducted a prospect i ve study in men with untreated prostate cancer to evaluate whether a 3-month dietary intervention affects the ratio of omega-3 to omega-6 fatty acids in plasma and gluteal fat . In addition , we evaluated the feasibility of study ing cyclooxygenase-2 ( COX-2 ) expression in serial prostate needle biopsy specimens before and after the diet . METHODS Nine men with untreated prostate cancer consumed an LF/FOS diet for 3 months . Plasma , gluteal adipose tissue , and prostate needle biopsy specimens were obtained from each patient before and after the intervention . The fatty acid compositions of the plasma and gluteal adipose tissue were determined by gas-liquid chromatography , and the COX-2 expression in the prostatic tissue specimens was determined by semiquantitative reverse transcriptase-polymerase chain reaction ( RT-PCR ) . RESULTS Short-term intervention with an LF/FOS diet caused a significant increase in the omega-3/omega-6 fatty acid ratio in plasma ( P = 0.002 ) and gluteal adipose tissue ( P = 0.002 ) in men with prostate cancer . The COX-2 expression in prostatic tissue was quantitated by RT-PCR in 7 of 9 patients , and COX-2 expression decreased in 4 of these 7 patients . CONCLUSIONS A short-term dietary intervention in men with prostate cancer leads to a significant increase in the omega-3/omega-6 fatty acid ratios in plasma and adipose tissue . The potential for this diet to prevent the development and progression of prostate cancer by way of altered COX-2 expression and prostagl and in production in prostatic tissue requires further study PURPOSE We performed a r and omized double-blind crossover pilot study in elderly men with elevated prostate specific antigen ( PSA ) on the effects of the daily consumption of 2 soy beverages , each containing 20 gm . of isolated soy protein , on the isoflavone concentration in blood and urine , and on the 3 serum biomarkers cholesterol , PSA and the soluble p105 component of the p185erbB-2 proto-oncogene . MATERIAL S AND METHODS A total of 34 men supplemented their diet by consuming 1 of 2 soy protein beverages assigned r and omly twice daily for a 6-week period . In a second 6-week period they consumed the other soy protein beverage . The beverage ISP+ provided 42 mg . of genistein and 27 mg . of daidzein daily , whereas the other beverage , ISP- , provided only 2.1 and 1.3 mg . of these isoflavones daily , respectively . Blood and 24-hour urine sample s were obtained before the study , at 2-week intervals during the study and 2 weeks after study completion . RESULTS ISP+ and to a lesser extent ISP- substantially increased the serum concentration and urinary output of the isoflavones and their metabolites . Serum cholesterol was significantly decreased by ISP+ irrespective of the order in which the 2 soy beverages were administered and in apparent correlation with the total isoflavone concentration . There was no significant effect of the soy beverages on serum PSA and p105erbB-2 values . CONCLUSIONS This study reveals that short-term exposure of elderly men with elevated serum PSA values to soy protein containing isoflavones decreases serum cholesterol but not the serum biomarkers PSA and p105erbB-2 |
10,354 | 11,601,957 | The systematic review ( 22 ) found that interventions aim ed at hospitalized patients may have the greatest effect on increasing influenza vaccinations .
The Advisory Committee on Immunization Practice s recommendation , which is based on an informal review of the literature , identifies st and ing orders as the most effective method to increase pneumococcal vaccination rates .
Quality Indicator 5 Influenza Vaccination of Health Care Workers IF a health care organization cares for vulnerable elders , THEN it should have a formal plan to offer and encourage influenza vaccination among its employees BECAUSE vaccination of health care workers is associated with reductions in total patient mortality and in the incidence of influenza-like illness .
Results of this study support recommendations for influenza vaccination of health care workers employed in long-term geriatric care .
Quality Indicator 6 Smoking Cessation IF a vulnerable elder smoker develops pneumonia , THEN the smoker should be advised to quit smoking BECAUSE interventions tailored for such acutely ill patients may increase the rate of long-term cessation of smoking .
This , in turn , may ultimately reduce the risk for developing recurrent pneumonia or other long-term complications of cigarette smoking .
A meta- analysis ( 36 ) and a large observational study , the Pneumonia Patient Outcomes Research Team ( PORT ) cohort study ( 37 ) , support the finding that interventions to advise smokers with pneumonia to quit smoking may increase the rate of long-term cessation of smoking . | Pneumonia is the most common cause of death from infection in persons 60 years of age and older and is the fourth most common cause of death overall for persons 80 years of age and older ( 1 ) .
Furthermore , the annual cost of treating patients with pneumonia in the United States is approximately $ 9.7 billion ( 2 ) , and most of this cost is incurred when patients ( the majority of whom are older ) are hospitalized .
It has been estimated that 962 patients per 100 000 persons 65 years and older will require hospitalization for pneumonia annually ; this figure is nearly four times the rate in the general population ( 3 ) .
The vulnerable older patient is at even greater risk for death and morbidity from pneumonia , and improving quality of care for this high-risk population may lead to substantial reductions in morbidity and mortality .
A meta- analysis of r and omized clinical trials demonstrates that the pneumococcal vaccine reduces the overall incidence of bacteremic pneumococcal pneumonia but is not effective in high-risk patients ( 5 ) .
The authors comment that if immunocompromised patients ( including those who have received a renal transplant or have renal failure , hematologic or metastatic cancer , the nephrotic syndrome , systemic lupus erythematosus , or sickle-cell anemia ) are removed from the analysis , the vaccine may show a benefit for the elderly because vaccination has been shown to increase antibody levels in elderly patients ( 6 , 7 ) .
Quality Indicator 2 Influenza Vaccine IF a vulnerable elder has no history of anaphylactic hypersensitivity to eggs or to other components of the influenza vaccine , THEN the patient should be offered an annual influenza vaccination BECAUSE the influenza vaccine is effective in limiting severe disease caused by influenza virus and is effective in elderly patients at all levels of risk .
A meta- analysis of 20 cohort studies , three casecontrol studies , two cost-effectiveness studies , and one r and omized , double-blind , placebo-controlled trial demonstrate that the influenza vaccine prevents pneumonia , hospitalization , and death in elderly persons and that it is cost-effective ( 18 ) .
The objectives of the Public Health Service for the year 2010 call for vaccinating at least 60 % of persons at risk for pneumococcal and influenza disease and 90 % of the institutionalized elderly ( 29 ) .
In 1997 , only 45 % of persons older than 65 years of age had ever received the pneumococcal vaccine , and the annual influenza rate for the elderly was 66 % ( 30 ) . | A prospect i ve analysis of patients hospitalized with pneumococcal infection at two Rochester ( NY ) hospitals was performed during an 18-month period to assess the feasibility of a pneumococcal vaccination program directed at in patients . Of the 113 patients hospitalized with pneumococcal infection , only nine patients ( 8 % ) had previously received pneumococcal vaccine and 76 patients ( 67 % ) had been hospitalized at least once in the previous three years . Of the 104 patients who had a source of regular medical care , 100 % had made at least one outpatient visit in the previous three years . The association between the acquisition of a serious pneumococcal infection and hospitalization within the previous three years suggests that a vaccination strategy directed at hospitalized high-risk patients would be potentially effective . Also , vaccination of high-risk ambulatory patients remains a viable strategy to prevent serious pneumococcal infection Pneumococcal vaccine effectiveness was assessed in a r and omized trial among 1,686 old people ( mean age : 74 , st and ard deviation : 4 years ) living in 24 geriatric hospitals and 26 homes for the aged in our district ; 937 were vaccinated with Merck-Sharp and Dohme pneumococcal vaccine ( 14 serotypes ) . The 749 others composed the reference group . This study was performed during 2 years , since December 1980 . Both groups were r and omized after a two- criteria stratification : by clinical risk assessed before the study , and by type of homes for the aged . Forty pneumonias were diagnosed , with 13 proved pneumococcal etiology . The incidence of pneumonia was significantly reduced in the vaccinated group ( p less than 10(-4 ) but the mortality rate was not modified . We concluded in favor of the effectiveness of pneumococcal vaccine : etiological fraction 77.1 % ( 51.2%-89.3 % confidence limits , 95 % risk ) in the population we studied . The incidence of pneumococcal-proved pneumonia was not significantly reduced CONTEXT Many groups have developed guidelines to shorten hospital length of stay in pneumonia in order to decrease costs , but the length of time until a patient hospitalized with pneumonia becomes clinical ly stable has not been established . OBJECTIVE To describe the time to resolution of abnormalities in vital signs , ability to eat , and mental status in patients with community-acquired pneumonia and assess clinical outcomes after achieving stability . DESIGN Prospect i ve , multicenter , observational cohort study . SETTING Three university and 1 community teaching hospital in Boston , Mass , Pittsburgh , Pa , and Halifax , Nova Scotia . PATIENTS Six hundred eighty-six adults hospitalized with community-acquired pneumonia . MAIN OUTCOME MEASURES Time to resolution of vital signs , ability to eat , mental status , hospital length of stay , and admission to an intensive care , coronary care , or telemetry unit . RESULTS The median time to stability was 2 days for heart rate ( < or = 100 beats/min ) and systolic blood pressure ( > or = 90 mm Hg ) , and 3 days for respiratory rate ( < or = 24 breaths/min ) , oxygen saturation ( > or = 90 % ) , and temperature ( < or = 37.2 degrees C [ 99 degrees F ] ) . The median time to overall clinical stability was 3 days for the most lenient definition of stability and 7 days for the most conservative definition . Patients with more severe cases of pneumonia at presentation took longer to reach stability . Once stability was achieved , clinical deterioration requiring intensive care , coronary care , or telemetry monitoring occurred in 1 % of cases or fewer . Between 65 % to 86 % of patients stayed in the hospital more than 1 day after reaching stability , and fewer than 29 % to 46 % were converted to oral antibiotics within 1 day of stability , depending on the definition of stability . CONCLUSIONS Our estimates of time to stability in pneumonia and explicit criteria for defining stability can provide an evidence -based estimate of optimal length of stay , and outline a clinical ly sensible approach to improving the efficiency of inpatient management OBJECTIVE To study the effect of a length of stay practice guideline on patient outcomes . DESIGN A prospect i ve , nonr and omized , interventional trial . SETTING Six geographically distributed hospitals . PATIENTS Two hundred forty-two consecutively hospitalized " low-risk " patients with pneumonia . MEASUREMENTS AND RESULTS One hundred fifty-two patients ( 63 % ) completed the mailed postdischarge survey and were included in the analysis . Data were prospect ively collected for 85 patients from the baseline observation period ( B ) and 67 patients from the intervention period ( I ) . During the I , case managers provided physicians with patient risk information based on guideline recommendations . There was no significant change in guideline compliance ( B vs I : 76.5 % vs 83.6 % ; p=0.32 ) or length of stay ( B vs I : 3.5 days [ 95 % confidence interval , 3.2 to 3.8 ] vs 3.6 days [ 95 % confidence interval , 3.3 to 4.0 ] ) . Also , there were no statistically significant effects of the intervention on patient outcomes , care following hospital discharge , and patient satisfaction scores . CONCLUSION Patients in this study often had shorter lengths of stay than recommended by the practice guideline . This suggests that the external environment may have had a greater effect on physician behavior and length of stay than the practice guideline itself . Moreover , it demonstrates the importance of continuous assessment of physician practice s immediately prior to , during , and after application of the clinical practice guideline This study compared three interventions design ed to increase acceptance of influenza and pneumococcal vaccines among elderly hospitalized patients . All individuals 65 and older able to give informed consent ( 73 patients ) who were admitted to one medical floor of an acute care hospital were r and omized to one of three groups . All groups received informational pamphlets explaining influenza and pneumococcal disease , their respective vaccines , and indications for their use . The first group received pamphlets only , the second received nursing follow-up , and the third received trained volunteer follow-up . Patients on another medical floor served as controls . The results showed a significant improvement in vaccine acceptance in all three study groups compared to controls for both influenza ( 78 % vs 0 % ) and pneumococcal ( 75 % vs 0 % ) vaccines . The differences among the three groups were not significant . No significant differences were found among patients accepting or refusing vaccination with regard to diagnosis , age , length of stay , sex , or having a private physician . We conclude that a simple educational program followed by offering vaccination before hospital discharge can be easily implemented , and dramatically increase immunization rates in this high risk group CONTEXT Large variations exist among hospitals in the use of treatment re sources for community-acquired pneumonia ( CAP ) . Lack of a common approach to the diagnosis and treatment of CAP has been cited as an explanation for these variations . OBJECTIVE To determine if use of a critical pathway improves the efficiency of treatment for CAP without compromising the well-being of patients . DESIGN Multicenter controlled clinical trial with cluster r and omization and up to 6 weeks of follow-up . SETTING Nineteen teaching and community hospitals in Canada . PATIENTS A total of 1743 patients with CAP presenting to the emergency department at 1 of the participating institutions between January 1 and July 31 , 1998 . INTERVENTION Hospitals were assigned to continue conventional management ( n = 10 ) or implement the critical pathway ( n = 9 ) , which consisted of a clinical prediction rule to guide the admission decision , levofloxacin therapy , and practice guidelines . MAIN OUTCOME MEASURES Effectiveness of the critical pathway , as measured by health-related quality of life on the Short-Form 36 Physical Component Summary ( SF-36 PCS ) scale at 6 weeks ; and re source utilization , as measured by the number of bed days per patient managed ( BDPM ) . RESULTS Quality of life and the occurrence of complications , readmission , and mortality were not different for the 2 strategies ; the 1-sided 95 % confidence limit of the between-group difference in the SF-36 PCS change score was 2.4 points , which was within a predefined 3-point boundary for equivalence . Pathway use was associated with a 1.7-day reduction in BDPM ( 4.4 vs 6.1 days ; P = .04 ) and an 18 % decrease in the admission of low-risk patients ( 31 % vs 49 % ; P = .01 ) . Although in patients at critical pathway hospitals had more severe disease , they required 1.7 fewer days of intravenous therapy ( 4.6 vs 6.3 days ; P = .01 ) and were more likely to receive treatment with a single class of antibiotic ( 64 % vs 27 % ; P<.001 ) . CONCLUSION In this study , implementation of a critical pathway reduced the use of institutional re sources without causing adverse effects on the well-being of patients BACKGROUND Vaccination rates for healthy senior citizens are lower than those for senior citizens with underlying medical conditions such as chronic heart or lung disease . Uncertainty about the benefits of influenza vaccination for healthy senior citizens may contribute to lower rates of utilization in this group . OBJECTIVE To clarify the benefits of influenza vaccination among low-risk senior citizens while concurrently assessing the benefits for intermediate- and high-risk senior citizens . METHODS All elderly members of a large health maintenance organization were included in each of 6 consecutive study cohorts . Subjects were grouped according to risk status : high risk ( having heart or lung disease ) , intermediate risk ( having diabetes , renal disease , stroke and /or dementia , or rheumatologic disease ) , and low risk . Outcomes were compared between vaccinated and unvaccinated subjects after controlling for baseline demographic and health characteristics . RESULTS There were more than 20000 subjects in each of the 6 cohorts who provided 147551 person-periods of observation . The pooled vaccination rate was 60 % . There were 101 619 person-periods of observation for low-risk subjects , 15 482 for intermediate-risk , and 30 450 for high-risk subjects . Vaccination over the 6 seasons was associated with an overall reduction of 39 % for pneumonia hospitalizations ( P<.001 ) , a 32 % decrease in hospitalizations for all respiratory conditions ( P<.001 ) , and a 27 % decrease in hospitalizations for congestive heart failure ( P<.001 ) . Immunization was also associated with a 50 % reduction in all-cause mortality ( P<.001 ) . Within the risk subgroups , vaccine effectiveness was 29 % , 32 % , and 49 % for high- , intermediate- , and low-risk senior citizens for reducing hospitalizations for pneumonia and influenza ( for high and low risk , P < or = .002 ; for intermediate risk , P = .11 ) . Effectiveness was 19 % , 39 % , and 33 % ( for each , P < or = .008 ) , respectively , for reducing hospitalizations for all respiratory conditions and 49 % , 64 % , and 55 % for reducing deaths from all causes ( for each , P<.001 ) . Vaccination was also associated with direct medical care cost savings of $ 73 per individual vaccinated for all subjects combined ( P = .002 ) . Estimates of cost savings within each risk group suggest that vaccination would be cost saving for each subgroup ( range of cost savings of $ 171 per individual vaccinated for high risk to $ 7 for low risk ) , although within the subgroups these findings did not reach statistical significance ( for each , P > or = .05 ) . CONCLUSIONS This study confirms that healthy senior citizens as well as senior citizens with underlying medical conditions are at risk for the serious complications of influenza and benefit from vaccination . All individuals 65 years or older should be immunized with this vaccine Since the introduction of the prospect i ve payment system ( PPS ) , anecdotal evidence has accumulated that patients are leaving the hospital " quicker and sicker . " We developed valid measures of discharge impairment and measured these levels in a nationally representative sample of patients with one of five conditions prior to and following the PPS implementation . Instability at discharge ( important clinical problems usually first occurring prior to discharge ) predicted the likelihood of postdischarge deaths . At 90 days postdischarge , 16 % of patients discharged unstable were dead vs 10 % of patients discharged stable . After the PPS introduction , instability increased primarily among patients discharged home . Prior to the PPS , 10 % of patients discharged home were unstable ; after the PPS was implemented , 15 % were discharged unstable , a 43 % relative change . Efforts to monitor the effect of this increase in discharge instability on health should be implemented OBJECTIVE To compare three approaches for improving compliance with influenza and pneumococcal vaccination of elderly patients . DESIGN R and omized controlled trial using three parallel group practice s at a public urban teaching hospital . SETTING Public teaching hospital . SUBJECTS All patients 65 years of age and older ( n = 1202 ) seen by resident physicians ( n = 66 ) attending three ambulatory medical practice s from October 1 , 1989 to March 31 , 1990 . INTERVENTIONS All three provider groups received intensive education in immunization st and ards . The control group received no further intervention . Staff in the second group offered education to patients at their visits . In the third group , the prevention team , a flowsheet was used , patient education offered , and staff had their tasks redefined to facilitate compliance ; for vaccinations , eg , nurses could vaccinate independent of MD initiative . MEASUREMENTS AND MAIN RESULTS Medical records were review ed for the 1202 patients seen , including 756 patients seen during both the 1988 - 89 and 1989 - 90 influenza seasons , to determine documented offering and receipt of vaccinations . During the intervention period ( 1989 - 90 ) , influenza vaccinations were offered significantly more frequently to prevention team patients ( 68.3 % ) than to patients in either the patient education ( 50.4 % ) or control ( 47.6 % ) groups ( P = 0.006 ) , even after adjusting for the patients ' prior vaccination status , age , gender , race , and high-risk co-morbidity and for physicians ' level of training . Likewise , pneumococcal vaccinations were offered more frequently to previously unvaccinated prevention team patients ( 28.3 % ) than to patient education ( 6.5 % ) or control ( 5.4 % ) group patients ( P = 0.001 ) , even after adjusting for the factors using multivariate analysis . Compliance rates did not differ between patient education and control subjects for either vaccine . Pre-intervention physician surveys documented higher perceived than actual compliance for both vaccines , with 89.0 % and 52.8 % of physicians believing that they complied with influenza and pneumococcal vaccination guidelines , respectively . CONCLUSIONS The results of this trial provide strong support for organizational changes that involve non-physician personnel to enhance vaccination rates among older adults There are few available data to define the medically necessary duration of stay for patients hospitalized with pneumonia . Therefore , we investigated the safety and effectiveness of a practice guideline that provided information about switching patients from parenteral to oral antimicrobials and early hospital discharge . The study was a prospect i ve controlled study with an alternate month design . The practice guideline was studied in 146 " low-risk " pneumonia patients hospitalized during a 22-month period . Medical care consistent with the practice guideline occurred in 64 % and 76 % of patients during control and intervention periods , respectively ( p=0.15 ) . There were no differences in patient outcomes in the control and intervention groups when measured 1 mo after hospital discharge , including hospital readmission rates , health-related quality of life , and patient satisfaction . Explicit and implicit review revealed that 98.6 % ( 95 % confidence interval [ CI ] : 95.1 % , 99.8 % ) of low-risk patients would not have benefited from continued hospitalization after the fourth hospital day . The 30-d survival rate of the low-risk pneumonia patients was 99.3 % ( 95 % CI : 96.2 % , 100 % ) and patient outcomes appeared to be favorable compared with previously published values . We conclude that duration of hospital stay was frequently consistent with the practice guideline in both study groups , and patient outcomes remained unchanged . The guideline will require additional testing before it can be recommended for use PURPOSE Few available data exist to define either the medically necessary duration of parenteral antimicrobial therapy or length of stay for hospitalized patients with pneumonia . Therefore , we investigated the potential safety and effectiveness of a practice guideline recommending early conversion of low-risk patients with pneumonia from parenteral to oral antimicrobial therapy and early hospital discharge . PATIENTS AND METHODS The practice guideline was studied retrospectively in 503 hospitalized patients with pneumonia at a teaching community hospital . RESULTS Thirty-three percent of patients with pneumonia were classified as at low risk for complications and potentially suitable for early conversion to oral antimicrobial therapy according to the guideline . Were the guideline to have been used to guide patient discharge decisions , 619 additional bed-days would have been made available to accommo date incoming patients . A consensus among physician review ers led to the judgment that quality of care would not have worsened for 98.2 percent of low-risk patients had they been switched to oral antimicrobial therapy on the third hospital day , nor would quality of care have been worsened for 93.4 percent of low-risk patients had they been discharged on the fourth hospital day . CONCLUSION The practice guideline that we studied has the potential to safely reduce the duration of parenteral antimicrobial therapy and length of hospital stay for selected low-risk patients with pneumonia . The guideline should be studied in a prospect i ve clinical trial Quality of care can be measured by using either processes or outcomes . Each method has its strengths and limitations ( 1 ) . With the concurrence of the Assessing Care of Vulnerable Elders ( ACOVE ) Policy Advisory Committee [ 2 ] , we chose to assess the care of vulnerable elders by using processes rather than outcomes . We did so because 1 ) processes are a more efficient measure of quality ; 2 ) for most conditions there are insufficient information in the medical record and a paucity of vali date d models to adequately adjust outcomes for differences in case mix between providers ; and 3 ) ultimately , processes of care are amenable to direct action by providers . To be a valid measure of quality , a health care process must be strongly linked to an outcome that is important to patients . Ideally , high- quality published studies would link performance of all such processes to outcomes ; however , few health care processes are supported by high- quality evidence ( 3 ) . Even when a process is supported by strong evidence from r and omized clinical trials , the inclusion and exclusion criteria of the clinical trials leave the evidence directly applicable to only a narrow group of patients ( 4 , 5 ) . This is particularly true for vulnerable elders , who are typically excluded from clinical trials ( 6 ) . Therefore , as we developed the ACOVE quality indicators , we used expert opinion to interpret the available evidence for applicability to vulnerable elders . Our methods entailed a literature review and several levels of expert opinion ( Figure ) , which we explain in detail . Figure . Assessing Care of Vulnerable Elders ( ACOVE ) method for developing quality indicators for vulnerable elders . Methods Development of Draft Process Indicators For each ACOVE condition that we selected for quality improvement in vulnerable elders ( 2 ) , we identified a content expert , who worked as a team with another project member knowledgeable about systematic review s and quality indicator development . Together , the content expert and project member developed potential quality indicators from existing guidelines , review criteria , and expert opinion . Because practice guidelines and existing quality indicators are seldom referenced in the traditional scientific data bases , we used various search strategies to locate these material s. In addition to search ing MEDLINE , we search ed the following sources : CONQUEST 1.1 ( A Computerized Needs-Oriented Quality Measurement Evaluation System ) ( 7 ) ; DEMPAQ : A Project to Develop and Evaluate Methods to Promote Ambulatory Care Quality ( 8) ; Directory of Clinical Practice Guidelines ( 9 ) ; Guide to Clinical Preventive Services ( 10 ) ; HEDIS 3.0 : Health Plan Employer Data and Information Set ( 11 ) ; National Guideline Clearinghouse ( 12 ) ; National Library of Health Care Indicators ( 13 ) ; and The Medical Outcomes & Guidelines Source book ( 14 ) . We also h and search ed the tables of contents of all issues of The Journal of the American Medical Association and Medical Care published April through November 1998 for relevant practice guidelines and quality indicators . Furthermore , we requested practice guidelines and quality indicators from the following agencies and organizations : Administration on Aging ( AOA ) ; Agency for Health Care Policy and Research (AHCPR)now known as Agency for Healthcare Research and Quality ( AHRQ ) ; Centers for Disease Control and Prevention ( CDC ) ; Department of Health and Human Services ( DHHS ) ; Department of Veterans Affairs ; Foundation for Accountability ( FACCT ) ; Health Care Financing Administration ( HCFA ) ; HCFA/Connecticut Peer Review Organization ; Joint Commission on Accreditation of Healthcare Organizations ( JCAHO ) ; National Committee for Quality Assurance ( NCQA ) ; and National Institutes of Health ( NIH ) . By using the quality indicators identified through this process , as well as using expert opinion and existing guidelines , the content expert developed 20 to 30 preliminary quality indicators for further review . Potential indicators were constructed in an IFTHENBECAUSE format : IF refers to the clinical characteristics that describe persons eligible for the quality indicator ; THEN indicates the actual process that should or should not be performed ; and BECAUSE refers to the expected health impact if the indicator is performed . For example , IF a vulnerable elder has heart failure with an ejection fraction of 40 % or less , THEN an angiotensin-converting enzyme ( ACE ) inhibitor should be offered BECAUSE treatment with ACE inhibitors improves longevity . We circulated this initial set of potential quality indicators to other clinical experts for their review . On the basis of review ers ' comments , we narrowed down the initial set to the 10 to 25 most promising indicators for future development . Review of Scientific Literature Next , we assessed the published evidence supporting a link between the process specified in each quality indicator and patient outcomes . To do so , we performed a systematic review on each quality indicator by using the essence of the Cochrane Collaboration 's methods (15)except that we used a single review er to screen and assess studies . With the assistance of a reference librarian , we electronically search ed MEDLINE , EMBASE , The Cochrane Data base of Systematic Review s , HealthSTAR , Ageline , and other specialized data bases on a condition-specific basis by using keywords and free-text terms to identify potentially relevant studies . For most conditions , the search es were not restricted by language . The content expert review ed the retrieved citations by using a three-step process : First , the titles were review ed for possibly relevant studies ; the abstract s associated with the titles that passed the first round of screening were then review ed ; and , finally , the full articles of abstract s that passed the second round of screening were review ed . Abstract s and articles were not masked for review . To be accepted , titles and abstract s had to contain information indicating that the full article probably reported evidence on the potential relationship between the process in question and better outcomes in humans . We excluded animal studies , letters , review articles , and other articles that did not report original data . In review ing full articles , we gave priority to evidence from studies with the strongest design s that were relevant to the potential quality indicator being examined . In general , this meant that we chose r and omized clinical trials for questions about the efficacy or effectiveness of interventions and prospect i ve cohort studies to answer questions about risk or prognosis . We considered such evidence to be direct evidence , and we judged direct evidence in elderly persons to be the strongest level of evidence available . In the absence of direct evidence in elderly persons , we performed search es for direct evidence in other groups . Indirect evidence that from less rigorous design sin elderly or nonelderly persons was review ed if the available direct evidence was insufficient . When both direct evidence and indirect evidence were lacking , we included the statements of authoritative bodies ( for example , specialty societies , National Institutes of Health consensus development conferences , or Agency for Health Care Policy and Research practice guidelines ) . After review ing all of the relevant articles , the content expert prepared a monograph detailing each of the quality indicators and summaries of the evidence supporting them . This monograph was sent to one or more peer review ers , who were asked to assess the quality of the monograph according to the following guidelines : 1 ) Is the review complete in terms of both the proposed quality criteria and the evidence ? 2 ) Is the review fair ( that is , is the presentation of the evidence unbiased ) ? The authors subsequently revised the monographs on the basis of review ers ' comments in a manner analogous to the response to a critique of a journal article : Each comment was addressed in turn , and the author provided an appropriate revision or stated the reason why he or she believed that no revision was indicated . Expert Panels We convened two multidisciplinary groups , each composed of 12 clinical experts , to interpret the supporting evidence detailed in the monographs and to select quality indicators for further consideration . Each panel of experts considered a separate set of ACOVE conditions . Table 1 lists the members of the panels and the conditions they considered . Table 1 . ACOVE Expert Panels To assess the expert opinions of the panelists , we used a modified version of the R AND /UCLA Appropriateness Method ( 16 , 17 ) . In brief , the method entails two rounds of anonymous ratings on a riskbenefit scale ranging from 1 to 9 and a face-to-face group discussion between rounds . Each panelist has equal weight in determining the final ratings . The reproducibility of the R AND /UCLA Appropriateness Method is consistent with that of well-accepted diagnostic tests , such as the interpretation of coronary angiography and screening mammography ( 18 ) . It also has content , construct , and predictive validity ( 5 , 17 , 19 , 20 ) . In this application of the method , we sent each panelist the proposed quality indicators and the relevant condition-specific monographs . We asked the panelists to assess the validity of each proposed indicator on a scale of 1 to 9 , in which 1 was definitely not valid and 9 was definitely valid . We considered an indicator to be valid if 1 ) adequate scientific evidence or professional consensus supported a link between the process specified by the indicator and a health benefit to the patient ; 2 ) a physician or health plan with high rates of adherence to the indicator would be considered a higher- quality provider ; and 3 ) the physician or health plan influenced a majority of factors that determine adherence to the indicator ( such as smoking cessation ) . Each panelist was instructed to rate each potential quality indicator for validity and return the ratings to us before the face-to-face BACKGROUND Three r and omized controlled trials of the effectiveness of pneumococcal vaccine in elderly and chronically ill adults in the United States have failed to show significant protective efficacy during 44,213 person-years of follow-up . Case-control studies have greater statistical power to detect significant prevention of rare diseases such as pneumococcal bacteremia , but they also have a greater susceptibility to bias , necessitating consistent results from multiple studies . Three case-control studies at two different universities have shown prevention of systemic infection , but another study found no benefit . METHODS Patients with pneumococcal bacteremia who were at least 2 years old and had chronic illness indicating the need for pneumococcal vaccine , or who were at least 65 years old were compared with matched control subjects for frequency of prior vaccination . Matching variables included date of admission , age , sex , race , type and duration of chronic illness serving as the major vaccine indication , number of vaccine indications and number of medical hospitalizations since licensure of the pneumococcal vaccine in 1978 , and type of primary medical care . RESULTS Pneumococcal vaccination was documented in the records of six ( 7 % ) of 85 cases and 26 ( 17 % ) of 152 control subjects , suggesting 81 % efficacy in conditional logistical regression analysis ( 95 % confidence interval , 34 % to 94 % , P = .008 ) . CONCLUSIONS Four case-control studies at three universities have now demonstrated significant protective efficacy of pneumococcal vaccine for preventing pneumococcal bacteremia . The development of antibiotic-resistant Streptococcus pneumoniae indicates an urgent need for an increased rate of vaccination among high-risk patients and for the development of more immunogenic conjugate vaccines that may enhance efficacy among elderly and immunocompromised patients as well as infants UNLABELLED To determine the proportion of patients who can be treated with early switch to oral antibiotics and early discharge , to evaluate clinical outcome and patient satisfaction for patients treated with early switch and early discharge , and to define the factors that interfere with early discharge for some of the patients who underwent early switch to oral antibiotic therapy . DESIGN Prospect i ve study . PARTICIPANTS Two hundred consecutive hospitalized patients with community-acquired pneumonia . MAIN OUTCOME MEASURES Number of days needed to switch to oral therapy and length of hospital stay . Clinical outcome and satisfaction with care were evaluated for those patients treated with early switch and early discharge . RESULTS Early switch to oral antibiotics ( within the first 3 days of hospitalization ) was performed in 133 patients ( 67 % ) . Clinical failure was documented in 1 patient . Early switch and early discharge was performed in 88 patients ( 44 % ) . The mean length of hospital stay for this group was 3.4 days . The most common reason for prolonged hospitalization after the switch to oral antibiotics was the need for diagnostic workup . More than 95 % of patients were satisfied with the care they had received . CONCLUSIONS Using simple clinical and laboratory criteria , a significant proportion of hospitalized patients with community-acquired pneumonia ( 44 % ) can be treated with early switch and early discharge . This model did not affect patient outcome , decreased the length of hospitalization , and was associated with a high level of patient satisfaction BACKGROUND Although the protective efficacy of pneumococcal polysaccharide vaccine has been demonstrated in r and omized trials in young African gold miners , there has been controversy about its efficacy in older Americans at risk for serious pneumococcal infections . To assess the vaccine 's protective efficacy against invasive pneumococcal infections , we conducted a hospital-based case-control study of the efficacy of pneumococcal vaccine in adults with a condition recognized to be an indication for receiving the vaccine . METHODS From 1984 to 1990 , adults in whom Streptococcus pneumoniae was isolated from any normally sterile site were identified by prospect i ve surveillance in the microbiology laboratories of 11 large hospitals ; those with an indication for pneumococcal vaccine were enrolled as case patients . For each case patient , one control was matched according to age , underlying illness , and site of hospitalization . We contacted all providers of medical care to ascertain each subject 's history of immunization with pneumococcal vaccine . Isolates of S. pneumoniae were serotyped by an investigator unaware of the subject 's vaccination history . RESULTS Thirteen percent of the 1,054 case patients and 20 percent of the 1,054 matched controls had received pneumococcal vaccine ( P less than 0.001 ) . When vaccine was given in either its 14-valent or its 23-valent form , its aggregate protective efficacy ( calculated as a percentage : 1 minus the odds ratio of having been vaccinated times 100 ) against infections caused by the serotypes represented in the vaccine was 56 percent ( 95 percent confidence interval , 42 percent to 67 percent ; P less than 0.00001 ) for all 983 patients infected with a serotype represented in the vaccine , 61 percent for a subgroup of 808 immunocompetent patients ( 95 percent confidence interval , 47 percent to 72 percent ; P less than 0.00001 ) , and 21 percent for a subgroup of 175 immunocompromised patients ( 95 percent confidence interval , -55 percent to 60 percent ; P = 0.48 ) . The vaccine was not efficacious against infections caused by serotypes not represented in the vaccine ( protective efficacy , -73 percent ; 95 percent confidence interval , -263 percent to 18 percent ; P = 0.15 ) . CONCLUSIONS Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumococcal infections in immunocompetent patients with indications for its administration . This vaccine should be used more widely We developed explicit process criteria and scales for Medicare patients hospitalized with congestive heart failure , myocardial infa rct ion , pneumonia , cerebrovascular accident , and hip fracture . We applied the process scales to a nationally representative sample of 14,012 patients hospitalized before and after the implementation of the diagnosis related group-based prospect i ve payment system . For the four medical diseases , a better process of care result ed in lower mortality rates 30 days after admission . Patients in the upper quartile of process scores had a 30-day mortality rate 5 % lower than that of patients in the lower quartile . The process of care improved after the introduction of the prospect i ve payment system ; eg , better nursing care after the introduction of the prospect i ve payment system was associated with an expected decrease in 30-day mortality rates in pneumonia patients of 0.8 percentage points , and better physician cognitive performance was associated with an expected decrease in 30-day mortality rates of 0.4 percentage points . Overall , process improvements across all four medical conditions were associated with a 1 percentage point reduction in 30-day mortality rates after the introduction of the prospect i ve payment system Abstract Vaccination of health care workers ( HCWs ) is recommended as a strategy for preventing influenza in elderly patients in long-term care . However , there have been no controlled studies to show whether this approach is effective . During the winter of 1994–1995 , 1059 patients in 12 geriatric medical long-term-care sites , r and omized for vac.cination of HCWs , were studied . In hospitals where HCWs were offered vaccination , 653 ( 61 % ) of 1078 were vaccinated . Vaccination of HCWs was associated with reductions in total patient mortality from 17 % to 10 % ( odds ratio [ OR ] , 0.56 ; 95 % confidence interval [ CI ] , 0.40–0.80 ) and in influenza-like illness ( OR , 0.57 ; 95 % CI , 0.34–0.94 ) . Vaccination of patients was not associated with significant effects on mortality ( OR , 1.15 ; 95 % CI , 0.81–1.64 ) . Results of this study support recommendations for vaccination against influenza of HCWs in long-term geriatric care . Vaccination of frail elderly long-term-care patients may not give clinical ly worthwhile benefits STUDY OBJECTIVES To determine the optimal treatment of empyema thoracis ( within the fibrinopurulent phase of illness ) comparing pleural drainage and fibrinolytic therapy vs video-assisted thoracoscopic surgery ( VATS ) , with regard to efficacy and duration of hospitalization . DESIGN Twenty patients with confirmed parapneumonic empyema thoracis were r and omized to chest tube pleural drainage plus streptokinase ( CT-SK ) vs VATS . SETTING University-based teaching hospital providing for Dallas County . PATIENTS AND METHODS Equivalent groups of patients with parapneumonic empyema thoracis were r and omized to receive either of two therapies : CT-SK ( n=9 ) or VATS ( n=11 ) . Outcomes analysis with respect to treatment efficacy , hospital duration , chest tube duration , hospital costs , and need for subsequent procedures was performed . RESULTS Each group suffered one mortality ( p = not significant ) . When compared with the CT-SK group , the VATS group had a significantly higher primary treatment success [ 10/11 , 91 % vs 4/9 , 44 % ; p<0.05 Fisher 's Exact Test ] , lower chest tube duration ( 5.8+/-1.1 vs 9.8+/-1.3 days ; p=0.03 ) , and lower number of total hospital days ( 8.7+/-0.9 vs 12.8+/-1.1 days ; p=0.009 ) . Clinical ly relevant but not statistically significant differences in hospital costs ( $ 16,642+/-2,841 vs $ 24,052+/-3,466 , p=0.11 ) also favored the VATS group . Of note , all the CT-SK treatment failures could be salvaged with VATS , and none required thoracotomy . CONCLUSIONS In patients with loculated , complex fibrinopurulent parapneumonic empyema thoracis , a primary treatment strategy of VATS is associated with a higher efficacy , shorter hospital duration , and less cost than a treatment strategy that utilizes catheter-directed fibrinolytic therapy BACKGROUND Switch therapy is defined as the early transition from intravenous to oral antibiotics during treatment of infection . This study was design ed to evaluate the clinical outcome and length of stay of hospitalized patients with community-acquired pneumonia treated with an early switch from intravenous to oral third-generation cephalosporins . METHODS Patients with a new roentgenographic pulmonary infiltrate and at least two symptoms ( cough , fever , or leukocytosis ) were enrolled in this study and treated with intravenous ceftizoxime sodium ( 1 g every 12 hours ) or ceftriaxone sodium ( 1 g every 24 hours ) . Patients were switched to oral cefixime ( 400 mg every 24 hours ) as soon as they met the following criteria : ( 1 ) resolution of fever ; ( 2 ) improvement of cough and respiratory distress ; ( 3 ) improvement of leukocytosis ; and ( 4 ) presence of normal gastrointestinal tract absorption . RESULTS Of the 120 patients enrolled , 75 ( 62 % ) had clinical data evaluated . Long-term follow-up showed that 74 patients ( 99 % ) were cured ; one patient required readmission for further intravenous therapy . Mean duration of hospital stay was 4 days . CONCLUSIONS This investigation demonstrated that an early switch to oral cefixime may be reasonable in hospitalized patients with community-acquired pneumonia who have already shown a good clinical and laboratory response to therapy with intravenous third-generation cephalosporins . This approach is clinical ly effective and minimizes hospital stay |
10,355 | 30,167,315 | All measures had good convergent and discriminant validity .
PROMIS provided the strongest evidence for known-group validity and reliability among generic instruments ; however , data on its responsiveness have not been published .
Across measures , st and ardised response means were generally indicative of poor-moderate sensitivity to longitudinal change .
In RCTs , clinical ly important improvements were reported in SF36 scores from baseline ; however , between-arm differences were frequently non-significant and non-important .
SF36 , PROMIS , LupusQoL and LIT had the strongest evidence for acceptable measurement properties , but few measures aside from the SF36 have been incorporated into clinical trials . | Inclusion of patient-reported outcomes is important in SLE clinical trials as they allow capture of the benefits of a proposed intervention in areas deemed pertinent by patients .
We aim ed to compare the measurement properties of health-related quality of life ( HRQoL ) measures used in adults with SLE and to evaluate their responsiveness to interventions in r and omised controlled trials ( RCTs ) . | In spite of current therapies , the overall health status of patients with SLE is poor . High-dose cyclophosphamide ( 50 mg/kg for 4 days ) with or without stem-cell rescue has been introduced as a new therapy for severe SLE , including renal and central nervous system (CNS)-SLE . Long-term durable responses have been found to be 40 % . A r and omised clinical trial was completed comparing high-dose cyclophosphamide with monthly intravenous cyclophosphamide ( 750 mg/m squared bovine serum albumin ) in patients with SLE who need cyclophosphamide for the first time . The primary outcome of the trial was complete clinical response . In this report , we compare the treatment groups with respect to quality of life . The patients in this study had a mean age of 35.3 ± 10.1 years , were of Caucasian ( 35 % ) , African-American ( 51 % ) , Hispanic ( 8 % ) and Asian ( 6 % ) people , and 88 % were women . The organ leading to treatment was renal lupus in 29 % , CNS-lupus in 45 % and other organs in 26 % . Quality of life was measured at each visit using the Medical Outcome Study Short-Form 36 ( SF-36 ) . At 6 months , the patients in the high-dose cyclophosphamide trial arm had significantly greater improvement than patients in the monthly intravenous cyclophosphamide arm ( P = 0.026 ; P = 0.0082 , respectively ) in the categories of general health and social functioning . At 18 months , the improvement in the role-physical score was significantly greater in the high-dose cyclophosphamide trial arm than in the monthly-dose cyclophosphamide arm ( P = 0.025 ) . At the end of the two and a half-year study , there were no significant differences between the groups with respect to changes in SF-36 . By pooling the groups , at 30 months , there was a statistically significant ( P < 0.05 ) improvement over baseline in 6 of the 8 SF-36 domains . This study shows earlier improvement in SF-36 measures at 6 months in the high-dose cyclophosphamide group but equal improvement in both arms at two and one and a half years . Eventual improvements in quality -of-life with both cyclophosphamide regimens are clinical ly meaningful to both patients and treating physicians Objective . To evaluate health-related quality of life ( HRQOL ) and corticosteroid use in patients with moderate to severely active SLE enrolled in two international , multicentre , r and omized controlled trials of epratuzumab ( ALLEVIATE-1 and -2 ) and a long-term extension study ( SL0006 ) . Methods . Ninety ALLEVIATE patients ( 43 % BILAG A , mean BILAG score 13.2 ) were r and omized to receive 360 mg/m2 ( n = 42 ) or 720 mg/m2 ( n = 11 ) epratuzumab or placebo ( n = 37 ) , plus st and ard of care , in 12-week cycles . Corticosteroid use , patient and physician global assessment s of disease activity ( PtGA and PGA ) and 36-item Medical Outcomes Survey Short Form ( SF-36 ) results were recorded at baseline and every 4 weeks . Both trials were prematurely discontinued due to a drug supply interruption ; patients followed for ≥6 months were analysed . Twenty-nine patients continued in SL0006 , with interim analysis at a median exposure of 120 ( range 13–184 ) weeks . Results . At week 12 , proportions of patients with a PGA ≥20 % above baseline or with a PtGA improvement greater than or equal to the minimum clinical ly important difference were higher in the epratuzumab arms than the placebo arm . PGA and PtGA improvements were sustained but did not reach statistical significance . At week 24 , mean cumulative corticosteroid doses with epratuzumab 360 and 720 mg/m2 were 1051 and 1973 mg less than placebo ( P = 0.034 and 0.081 , respectively ) . At week 48 , SF-36 scores approached or exceeded US age- and gender-matched norms in five domains with the 360 mg/m2 treatment . Improvements were maintained in SL0006 over ∼2 years . Conclusion . Epratuzumab treatment produced clinical ly meaningful and sustained improvements in PGA , PtGA and HRQOL and reductions in corticosteroid doses OBJECTIVE B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus ( SLE ) , and rituximab induces depletion of B cells . The Exploratory Phase II/III SLE Evaluation of Rituximab ( EXPLORER ) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE . METHODS Patients entered with > or=1 British Isles Lupus Assessment Group ( BILAG ) A score or > or=2 BILAG B scores despite background immunosuppressant therapy , which was continued during the trial . Prednisone was added and subsequently tapered . Patients were r and omized at a ratio of 2:1 to receive rituximab ( 1,000 mg ) or placebo on days 1 , 15 , 168 , and 182 . RESULTS In the intent-to-treat analysis of 257 patients , background treatment was evenly distributed among azathioprine , mycophenolate mofetil , and methotrexate . Fifty-three percent of the patients had > or=1 BILAG A score at entry , and 57 % of the patients were categorized as being steroid dependent . No differences were observed between placebo and rituximab in the primary and secondary efficacy end points , including the BILAG-defined response , in terms of both area under the curve and l and mark analyses . A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups . Safety and tolerability were similar in patients receiving placebo and those receiving rituximab . CONCLUSION The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse . No differences were noted between placebo and rituximab in the primary and secondary end points . Further evaluation of patient subsets , biomarkers , and exploratory outcome models may improve the design of future SLE clinical trials Objectives The aim was to evaluate the cross-cultural validity of the Lupus Impact Tracker ( LIT ) in five European countries and to assess its acceptability and feasibility from the patient and physician perspectives . Methods A prospect i ve , observational , cross-sectional and multicentre validation study was conducted in clinical setting s. Before the visit , patients completed LIT , Short Form 36 ( SF-36 ) and care satisfaction question naires . During the visit , physicians assessed disease activity [ Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI ] , organ damage [ SLICC/ACR damage index ( SDI ) ] and flare occurrence . Cross-cultural validity was assessed using the Differential Item Functioning method . Results Five hundred and sixty-nine SLE patients were included by 25 specialists ; 91.7 % were out patients and 89.9 % female , with mean age 43.5 ( 13.0 ) years . Disease profile was as follows : 18.3 % experienced flares ; mean SELENA-SLEDAI score 3.4 ( 4.5 ) ; mean SDI score 0.8 ( 1.4 ) ; and SF-36 mean physical and mental component summary scores : physical component summary 42.8 ( 10.8 ) and mental component summary 43.0 ( 12.3 ) . Mean LIT score was 34.2 ( 22.3 ) ( median : 32.5 ) , indicating that lupus moderately impacted patients ' daily life . A cultural Differential Item Functioning of negligible magnitude was detected across countries ( pseudo- R 2 difference of 0.01 - 0.04 ) . Differences were observed between LIT scores and Physician Global Assessment , SELENA-SLEDAI , SDI scores = 0 ( P < 0.035 ) and absence of flares ( P = 0.004 ) . The LIT showed a strong association with SF-36 physical and social role functioning , vitality , bodily pain and mental health ( P < 0.001 ) . The LIT was well accepted by patients and physicians . It was reliable , with Cronbach α coefficients ranging from 0.89 to 0.92 among countries . Conclusion The LIT is vali date d in the five participating European countries . The results show its reliability and cultural invariability across countries . They suggest that LIT can be used in routine clinical practice to evaluate and follow patient-reported outcomes in order to improve patient-physician interaction Introduction A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus ( SLE ) found reduction of antioxidants and substrates for energy generation . These metabolic alterations may underlie one of the most common features of SLE - fatigue . The metabolomic studies also noted reduced omega-3 fatty acids , which are powerful anti- oxidants . This deficiency may be causally related to oxidative stress , inflammation , disease activity , and fatigue in SLE . Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies . The objective of this study is to evaluate the effect of fish oil supplementation on clinical measures of fatigue , quality of life , and disease activity as part of a r and omized clinical trial . Methods Fifty SLE patients recruited in outpatient clinics were r and omized 1:1 to fish oil supplementation or olive oil placebo , and blinded to their treatment group . At baseline and after 6 months of treatment , R AND Short Form-36 ( R AND SF-36 ) , Fatigue Severity Scale ( FSS ) , SLE Disease Activity Index ( SLEDAI ) , and Physician Global Assessment ( PGA ) were completed ; serum was also collected for soluble mediator analysis . Results Thirty-two patients completed the study . PGA improved significantly in the fish oil group compared with the placebo group ( p = 0.015 ) . The R AND SF-36 Energy/fatigue and Emotional well-being scores demonstrated improvement trends ( p = 0.092 and 0.070 ) . No clear difference was seen in FSS and SLEDAI ( p = 0.350 and p = 0.417 ) . Erythrocyte sedimentation rate and serum IL-12 were reduced ( p = 0.008 and p = 0.058 ) ; while serum IL-13 was increased by fish oil supplementation ( p = 0.033 ) . Conclusions In this r and omized , placebo-controlled 6-month trial , SLE patients r and omized to fish oil supplementation demonstrated improvement in their PGA , R AND SF-36 , and some circulating inflammatory markers . Trial registration Clinical Trials.gov Identifier : NCT02021513 ( registered 13 December 2013 ) Introduction This trial evaluated the safety , biologic activity , and pharmacokinetics of belimumab , a fully human monoclonal antibody that inhibits the biologic activity of the soluble form of the essential B-cell survival factor B-lymphocyte stimulator ( BLyS ) in patients with systemic lupus erythematosus ( SLE ) . Methods Seventy patients with mild-to-moderate SLE were enrolled in a phase I , double-blind , r and omized study and treated with placebo ( n = 13 ) or belimumab ( n = 57 ) at four different doses ( 1.0 , 4.0 , 10 , and 20 mg/kg ) as a single infusion or two infusions 21 days apart . Patients were followed for 84 to 105 days to assess adverse events , pharmacokinetics , peripheral blood B-cell counts , serology , and SLE disease activity . Data from the study were summarized using descriptive statistics . χ2 type tests were used to analyze discrete variables . The Kruskal-Wallis test , the Wilcoxon test , and the analysis of covariance were used to analyze the continuous variables , as appropriate . The analysis was performed on all r and omized patients who received study agent . Results The incidences of adverse events and laboratory abnormalities were similar among the belimumab and placebo groups . Belimumab pharmacokinetics were linear across the 1.0 to 20 mg/kg dose range . Long terminal elimination half-life ( 8.5 to 14.1 days ) , slow clearance ( 7 ml/day per kg ) , and small volume of distribution ( 69 to 112 ml/kg ) were consistent with a fully human antibody . Significant reductions in median percentages of CD20 + B cells were observed in patients treated with a single dose of belimumab versus placebo ( day 42 : P = 0.0042 ; and day 84 : P = 0.0036 ) and in patients treated with two doses of belimumab versus placebo ( day 105 : P = 0.0305 ) . SLE disease activity did not change after one or two doses of belimumab . Conclusions Belimumab was well tolerated and reduced peripheral B-cell levels in SLE patients . These data support further studies of belimumab in autoimmune disorders . Trial Registration NCT00657007 [ clinical trials.gov ] Background Patients with proliferative lupus nephritis are at risk of frequent relapses . Whether low- dose prednisone prevents relapses is uncertain . Objectives We undertook a pilot RCT to determine the feasibility of a larger trial . Design Pilot r and omized controlled trial . Setting Single center Canadian outpatient nephrology clinic . Patients Participants with systemic lupus erythematosus ( SLE ) and a history of class III or IV lupus nephritis that achieved at least partial remission and remained on prednisone were eligible . Measurements Feasibility : proportion of eligible patients r and omized and adherence to tapering regimen . Clinical : occurrence of renal or major non-renal flare of SLE . Methods We conducted a blinded , two-parallel-group r and omized controlled trial of prednisone 7.5 mg/day ( continuation ) compared to a matching placebo ( withdrawal ) . Results Of nineteen eligible patients screened , 15 ( 79 % ) were recruited and r and omized ; 8 to prednisone continuation and seven to withdrawal . All participants adhered to the tapering protocol to their assigned withdrawal or low-dose maintenance target . Over 36 months , the primary outcome occurred in four ( 50 % ) patients in the continuation group ( three renal and one major non-renal flare ) , compared with one patient ( 14 % ) in the withdrawal group ( one renal flare ) . Three participants ( 38 % ) in the continuation group had minor flares , while no patients in the withdrawal group did . Limitations This pilot RCT was small and not design ed to assess the efficacy or safety of maintenance with low-dose prednisone . Conclusions The high proportion of eligible patients recruited , and success of protocol adherence suggest a large trial of prednisone maintenance therapy compared to withdrawal is feasible . Trial registration Current Controlled Trials IS RCT N31327267.Abrégé Context eLes patients atteints de néphropathie lupique proliférative sont sujets à de nombreuses rechutes . Il est incertain que l’administration de faibles doses de prednisone aide à prévenir ses rechutes . ObjectifsNous avons entrepris un essai r and omisé contrôlé ( ERC ) ( étude pilote ) afin de déterminer la faisabilité d’une étude plus vaste . Type d’étudeEssai r and omisé contrôlé ( étude pilote ) . Context eLa clinique externe de néphrologie d’un centre canadien . Patients Les personnes atteintes de lupus érythémateux disséminé ( LED ) , avec antécédents de néphropathie lupique de stades III et IV , en rémission ( minimalement partielle ) et toujours en traitement de maintien sous prednisone étaient admissibles à l’étude . MesuresFaisabilité : Assignation aléatoire à partir de l’échantillon des patients admissibles et observance de la posologie dégressive . Clinique : apparition d’une poussée lupique rénale ou d’une poussée lupique grave non rénale . MéthodeNous avons mené un essai clinique aléatoire , en parallèle et à double insu , d’un groupe sous 7,5 mg de prednisone ( traitement continu ) et d’un groupe sous placebo (sevrage).RésultatsDu bassin des dix-neuf patients triés , 15 d’entre eux ( 79 % ) ont été sélectionnés . Le choix du traitement a été attribué de façon aléatoire : 8 patients pour le traitement de maintien sous prednisone et 7 patients pour le sevrage . Tous les participants ont observé le protocol e de posologie dégressive qui leur était attribué et do nt le but était le sevrage ou le maintien avec de faibles doses de prednisone . Sur une période de 36 mois , le premier indicateur des résultats est apparu chez quatre patients ( 50 % ) du groupe sous prednisone à faible dose ( trois poussées rénales et une poussée grave non rénale ) , comparativement à un patient ( 14 % ) du groupe sous sevrage ( une poussée rénale ) . Trois des participants ( 38 % ) du groupe sous prednisone à faible dose ont eu des poussées lupiques mineures ; aucune poussée lupique mineure n’est apparue dans le groupe sous placebo . Limites de l’étudeCet essai r and omisé contrôlé pilote a été effectué sur un petit groupe ; il n’a pas été conçu pour évaluer l’efficacité ou la sûreté d’un entretien sous prednisone à faible dose . Conclusion Le succès combiné du large échantillon de départ de patients admissibles et l’observance du protocol e de posologie dégressive laisse suggérer qu’une étude plus vaste comparant le traitement de maintien à la prednisone et le sevrage est faisable The objective of this study was to evaluate the efficacy of low dose dehydroepi and rosterone ( DHEA ) on health-related quality of life ( HRQOL ) in glucocorticoid treated female patients with systemic lupus erythematosus ( SLE ) . Forty one women ( ≥ 5 mg prednisolone/day ) were included in a double-blind , r and omized , placebo-controlled study for 6 months where DHEA was given at 30 mg/20 mg ( ≤ 45/ ≥ 46 years ) daily , or placebo , followed by 6 months open DHEA treatment to all patients . HRQOL was assessed at baseline , 6 and 12 months , using four vali date d question naires and the patients ' partners completed a question naire assessing mood and behaviour at 6 months . DHEA treatment increased serum levels of sulphated DHEA from subnormal to normal . The DHEA group improved in SF-36 “ role emotional ” and HSCL-56 total score ( both p < 0.05 ) . During open DHEA treatment , the former placebo group improved in SF-36 “ mental health ” ( p < 0.05 ) with a tendency for improvement in HSCL-56 total score ( p = 0.10 ) . Both groups improved in McCoy 's Sex Scale during active treatment ( p < 0.05 ) . DHEA replacement decreased high-density lipoprotein ( HDL ) cholesterol and increased insulin-like growth factor I ( IGF-I ) and haematocrit . There were no effects on bone density or disease activity and no serious adverse events . Side effects were mild . We conclude that low dose DHEA treatment improves HRQOL with regard to mental well-being and sexuality and can be offered to women with SLE where mental distress and /or impaired sexuality constitutes a problem OBJECTIVE The Medical Outcomes Short Form-36 Survey ( SF-36 ) has been widely used as a measure of health-related quality of life ( HRQOL ) in different population s. SLE patients have consistently reported lower scores compared with the general population . The objective of our study was to identify predictors of HRQOL using SF-36 among patients with SLE enrolled in a 2-year r and omized controlled trial ( RCT ) . METHODS We analysed 200 SLE patients enrolled in the Lupus Atherosclerosis Prevention Study ( LAPS ) , an RCT of atorvastatin vs placebo , who completed SF-36 at qualifying , 12- and 24-month ( final ) visits . RESULTS At baseline , mean SF-36 domain scores were lower than those of age- and gender-matched population norms . There was no statistical difference reported between Physical Component Summary ( PCS ) , Mental Component Summary and eight domain scores in the atorvastatin vs placebo group at 2 years . In multiple regression analyses , African American patients reported significantly lower scores in Physical Functioning compared with Caucasians . The presence of FM was significantly associated with lower scores in physical functioning , role physical , bodily pain , general health , vitality , social functioning and lower overall mean PCS scores . The Physician 's Global Assessment of disease activity was associated with multiple SF-36 domains in univariate analysis . CONCLUSION This longitudinal study confirmed lower scores reported across all SF-36 domains . No one explanatory variable was independently associated with all domain scores . FM was independently associated with poorer HRQOL in most domains , underscoring the need for effective treatments for FM in SLE Objective Assess the effects of belimumab treatment plus st and ard systemic lupus erythematosus ( SLE ) therapy on health-related quality of life ( HRQOL ) in patients with active , autoantibody-positive SLE . Methods Patients received st and ard therapy plus placebo or belimumab 1 or 10 mg/kg in two multicentre , r and omised controlled trials of 52 ( BLISS-52 ; N=865 ) and 76 ( BLISS-76 ; N=819 ) weeks ’ duration . Responders were evaluated by SLE Responder Index at week 52 . Patient-reported outcome assessment s included SF-36 , Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue , and EQ-5D . Results Mean SF-36 Physical Component Summary ( PCS ) scores at week 24 was a major secondary endpoint . Baseline SF-36 scores were 1.5 SDs below age-/sex-matched US norms with similar improvement at week 24 across treatment groups . Mean changes from baseline in PCS scores were significantly ( p<0.05 ) greater with belimumab 1 mg/kg ( 4.20 ) and 10 mg/kg ( 4.18 ) versus placebo ( 2.96 ) in BLISS-52 , week 52 . In BLISS-76 , significantly ( p<0.05 ) greater improvements were seen with belimumab 1 mg/kg in PCS ( belimumab 1 mg/kg=4.37 , 10 mg/kg=3.41 vs placebo=2.85 ) and Mental Component Summary ( MCS ) scores ( belimumab 1 mg/kg=3.14 , 10 mg/kg=2.70 vs placebo=1.40 ) at week 52 , and in MCS score at week 76 ( belimumab 1 mg/kg=3.05 , 10 mg/kg=2.28 vs placebo=1.36 ) . In pooled analysis , significantly greater improvements in PCS , SF-36 vitality domain , and FACIT-Fatigue scores at week 52 were evident with both belimumab doses . Conclusions The clinical ly meaningful improvements in HRQOL in autoantibody-positive patients with active SLE treated with belimumab and st and ard therapy are consistent with the reductions in disease activity observed in these trials . Clinical Trials.gov number NCT00424476 , NCT00410384 Objectives To identify factors that predict response to belimumab treatment in the phase 3 BLISS trials of autoantibody-positive systemic lupus erythematosus ( SLE ) and further analyse clinical efficacy in various patient subsets . Methods The BLISS trials compared belimumab 1 and 10 mg/kg versus placebo , all plus st and ard SLE therapy , over 52 or 76 weeks . Pooled subgroup analyses of week 52 SLE responder index rates ( the primary endpoint in both trials ) were performed based on demographic characteristics and baseline disease activity indicators . Pooled multivariate analysis was performed to determine predictors of response and treatment effect . Results Pooled univariate and multivariate analyses ( N=1684 ) identified baseline factors associated with an increased benefit of belimumab versus placebo . These factors included the Safety Of Estrogens In Lupus Erythematosus National Assessment –Systemic Lupus Erythematosus Disease Activity Index ( SELENA – SLEDAI ) ≥10 , low complement , anti-dsDNA positivity and corticosteroid use . Efficacy outcomes were assessed in the low complement/anti-dsDNA-positive and SELENA – SLEDAI ≥10 subgroups . Week 52 SLE Responder Index rates in the low complement/anti-dsDNA-positive subgroup were 31.7 % , 41.5 % ( p=0.002 ) and 51.5 % ( p<0.001 ) with placebo and belimumab 1 mg/kg and 10 mg/kg , respectively ; corresponding rates in the SELENA – SLEDAI ≥10 subgroup were 44.3 % , 58.0 % ( p<0.001 ) and 63.2 % ( p<0.001 ) . Further analysis of secondary endpoints in the low complement/anti-dsDNA-positive subgroup showed that compared with placebo , belimumab produced greater benefits regarding severe flares , corticosteroid use and health-related quality of life . Conclusions These findings suggest that belimumab has greater therapeutic benefit than st and ard therapy alone in patients with higher disease activity , anti-dsDNA positivity , low complement or corticosteroid treatment at baseline . Clinical Trials.gov identifiers NCT00424476 and Objectives This phase II trial evaluated the efficacy and safety of an interleukin ( IL ) 6 monoclonal antibody for systemic lupus erythematosus ( SLE ) . Methods Patients with active disease were r and omised to placebo or PF-04236921 10 mg , 50 mg or 200 mg , subcutaneously , every 8 weeks with stable background therapy . SLE Responder Index ( SRI-4 ; primary end point ) and British Isles Lupus Assessment Group-based Composite Lupus Assessment ( BICLA ) were assessed at week 24 . Post hoc analysis identified an enriched population based upon planned univariate analyses . Results 183 patients received treatment ( placebo , n=45 ; 10 mg , n=45 ; 50 mg , n=47 ; 200 mg , n=46 ) . The 200 mg dose was discontinued due to safety findings and not included in the primary efficacy analysis . The SRI-4 response rates were not significant for any dose compared with placebo ; however , the BICLA response rate was significant for 10 mg ( p=0.026 ) . The incidence of severe flares was significantly reduced with 10 mg ( n=0 ) and 50 mg ( n=2 ) combined versus placebo ( n=8 ; p<0.01 ) . In patients with greater baseline disease activity ( enriched population ) , the SRI-4 ( p=0.004 ) and BICLA ( p=0.012 ) response rates were significantly different with 10 mg versus placebo . Four deaths ( 200 mg , n=3 ; 10 mg , n=1 ) occurred . The most frequently reported adverse events included headache , nausea and diarrhoea . Conclusions PF-04236921 was not significantly different from placebo for the primary efficacy end point in patients with SLE . Evidence of an effect with 10 mg was seen in a post hoc analysis . Safety was acceptable for doses up to 50 mg as the 200 mg dose was discontinued due to safety findings . Trial registration number NCT01405196 ; Pre- results We present data from two studies which clarify the relationship between the responsiveness and validity of instruments design ed to measure health status in clinical trials . In a controlled trial of long vs short duration adjuvant chemotherapy for women with Stage II breast cancer , the Breast Cancer Chemotherapy Question naire ( BCQ ) proved valid as a measure of subjective health status and was able to distinguish long vs short arms . Well vali date d measures of physical and emotional function developed by the R and Corporation were unable to distinguish between the two groups . The Eastern Co-operative Oncology Group Criteria ( ECOG ) distinguished the two groups , but failed criteria of clinical sensibility as a measure of subjective health status . In a study of patients with Crohn 's disease and ulcerative colitis , the Inflammatory Bowel Disease Question naire ( IBDQ ) showed small intrasubject variability over time . Gobal ratings of change showed moderate to high correlations with changes in IBDQ score , and patients who reported overall improvement or deterioration showed large changes in IBDQ score . Each of these findings support , in different ways , the reproducibility , validity , and responsiveness of the question naire . While the same data can at times bear on both validity and responsiveness , when assessing evaluative instruments it is useful to make a conceptual distinction between the two OBJECTIVE To prospect ively identify factors influencing quality of life ( QOL ) over 6 months in patients with systemic lupus erythematosus ( SLE ) . METHODS Ninety ethnically diverse patients with SLE completed question naires administered 6 months apart assessing QOL ( using the Medical Outcomes Study Short Form-36 ) and demographic , socioeconomic , psychosocial , and behavioral factors . Disease activity , damage , and treatment were recorded at both evaluations . Multiple linear regression ( adjusting for baseline health status ) was used to identify factors influencing mental and physical health . RESULTS Improved physical health after 6 months was associated with reductions in learned helplessness ( p = 0.034 ) , improved mental health ( p<0.001 ) , longer disease duration ( p = 0.009 ) , and better physical health at baseline ( p = 0.027 ) . Improved mental health after 6 months was associated with better family support ( p = 0.002 ) , improvements in physical health ( p<0.001 ) , disease activity , and prednisolone dose ( interaction term p = 0.019 ) , less disease related damage ( p<0.001 ) , non-use of cytotoxic drugs ( p = 0.02 ) , and older age at diagnosis ( p = 0.007 ) . CONCLUSION Potentially modifiable psychosocial , disease , and therapy related factors influence QOL in patients with SLE OBJECTIVE To assess the safety , tolerability , biologic activity , and efficacy of belimumab in combination with st and ard of care therapy ( SOC ) in patients with active systemic lupus erythematosus ( SLE ) . METHODS Patients with a Safety of Estrogens in Lupus Erythematosus : National Assessment ( SELENA ) version of the Systemic Lupus Erythematosus Disease Activity Index ( SLEDAI ) score > /=4 ( n = 449 ) were r and omly assigned to belimumab ( 1 , 4 , or 10 mg/kg ) or placebo in a 52-week study . Co primary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare . RESULTS Significant differences between the treatment and placebo groups were not attained for either primary end point , and no dose response was observed . Reductions in SELENA-SLEDAI scores from baseline were 19.5 % in the combined belimumab group versus 17.2 % in the placebo group . The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group . However , the median time to first SLE flare during weeks 24 - 52 was significantly longer with belimumab treatment ( 154 versus 108 days ; P = 0.0361 ) . In the subgroup ( 71.5 % ) of serologically active patients ( antinuclear antibody titer > /=1:80 and /or anti-double-str and ed DNA [ anti-dsDNA ] > /=30 IU/ml ) , belimumab treatment result ed in significantly better responses at week 52 than placebo for SELENA-SLEDAI score ( -28.8 % versus -14.2 % ; P = 0.0435 ) , physician 's global assessment ( -32.7 % versus -10.7 % ; P = 0.0011 ) , and Short Form 36 physical component score ( + 3.0 versus + 1.2 points ; P = 0.0410 ) . Treatment with belimumab result ed in a 63 - 71 % reduction of naive , activated , and plasmacytoid CD20 + B cells , and a 29.4 % reduction in anti-dsDNA titers ( P = 0.0017 ) by week 52 . The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups . CONCLUSION Belimumab was biologically active and well tolerated . The effect of belimumab on the reduction of SLE disease activity or flares was not significant . However , serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone OBJECTIVES And rogen deficiency has been associated with the development of systemic lupus erythematosus ( SLE ) . The aim of this study was to test the efficacy of testosterone patches vs placebo in female SLE patients with baseline mild-to-moderate disease activity in a r and omized , double-blind , single-centre placebo-controlled trial . METHODS Patients received testosterone ( 150 microg ) or placebo transdermal patches for 12 weeks . Patients were assessed at 4-weekly intervals for disease activity using the Safety of Oestrogens in Lupus Erythematosus National Assessment -SLE Disease Activity Index ( SELENA-SLEDAI ) , Systemic Lupus Activity Measure-Revised ( SLAM-R ) and The British Isles Lupus Assessment Group ( BILAG ) indices , physician global assessment ( PGA ) , quality of life using the SF-36 survey and sexual functioning using the Derogatis score . Data were analysed using two sample t-tests to compare the mean difference from baseline to week 12 in the testosterone patch and placebo groups . RESULTS Thirty-four patients were recruited in to each group . There was no significant baseline difference between the groups in age , race or marital status . There was no significant difference between treatment groups in the mean change in SELENA-SLEDAI ( 0.547 + /- 3.72 , P > 0.60 ) , nor in PGA or BILAG system scores . The mean change in SLAM-R score was statistically different ( 2.06 , S.D. 3.3 , P = 0.01 ) but was not considered clinical ly meaningful . Health transition also showed a small change ( P < 0.03 ) . There was no significant difference in the Derogatis scores or toxicity . CONCLUSIONS Testosterone patches were safe but did not significantly affect disease activity , quality of life or sexual functioning . Increased use of steroids in the placebo group may have confounded the study results OBJECTIVE To assess the reliability and construct validity of the Medical Outcomes Study Short Form 36 Health Survey ( SF-36 ) in a multiracial cohort of Asian patients with lupus in Singapore . METHODS A cross sectional study was performed on 118 English speaking patients with lupus attending a specialist rheumatology unit between March and August 1996 . Patients completed a question naire containing the UK st and ard version of the SF-36 twice within a 14 day period . All patients were assessed for disease activity using the British Isles Lupus Assessment Group score ( BILAG ) , and for disease related damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology ( SLICC/ACR ) damage index ( DI ) . Relationships between SF-36 , BILAG , and DI scores were studied using Spearman 's rank correlation . Internal consistency of the SF-36 was assessed using Cronbach 's alpha , and stability using the repeatability coefficient of Bl and and Altman . RESULTS SF-36 subscales showed high internal consistency , with Cronbach 's alpha coefficient ranging from 0.84 to 0.94 . Test-retest reliability was acceptable , with Spearman 's rank correlation > 0.70 for all subscales except role-physical , and mean differences in test scores of < 2 points for 5 of 8 subscales . SF-36 subscale scores were weakly correlated with BILAG scores ( Spearman 's p -0.37 to 0.15 ) and SLICC/ACR DI scores ( Spearman 's p -0.25 to 0.23 ) , suggesting divergent construct validity of the SF-36 . CONCLUSION These data suggest the SF-36 is a reliable and valid measure of the quality of life of patients with lupus in Singapore OBJECTIVE To investigate the metric properties and validity of the assessment of quality of life by the MOS Short Form 36 ( SF-36 ) in patients with systemic lupus erythematosus ( SLE ) and to examine the effect of disease on quality of life . METHODS Cross sectional study of 150 patients with SLE ( age : mean 39.7 yrs , SD 11.4 yrs ; 95 % female ) attending 2 specialist lupus clinics between November 1994 and April 1995 . Shortly before or after the consultation patients completed the SF-36 and the MOS SF-20 with an additional question about fatigue ( SF-20 + ) in r and om order . Disease activity was measured by the British Isles Lupus Activity Group System ( BILAG ) , disease damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology ( SLICC/ACR ) damage index ( SLICC ) . RESULTS SF-36 domains were shown to be internally consistent ( Cronbach 's coefficient alpha > or = 0.71 ) . Significant associations of the SF-36 domains with the corresponding domains of the SF-20 + and with global disease activity measured by BILAG were observed . SF-36 scores in patients with SLE were significantly lower than in controls . Different disease activity levels were significantly associated with different quality of life scores , with excellent ability to record the continuum from good health to serious illness by the SF-36 . Disease activity had greater effect on quality of life than age , cumulative damage , or disease duration . CONCLUSION This study shows the SF-36 is internally consistent and proves construct , discriminatory , and criterion validity for the SF-36 and construct validity for the SF-20 + in patients with SLE . The SF-36 is preferred because of its broader scope of questions , its widespread use , and previous international validation for a wide variety of diseases This report evaluates the effects of blisibimod ( A-623 , AMG 623 ) , a potent and selective inhibitor of B-cell activating factor ( BAFF ) , on patient-reported fatigue and disease activity in the Phase 2b PEARL-SC clinical trial in patients with systemic lupus erythematosus ( SLE ) . A total of 547 individuals who met the American College of Rheumatology ( ACR ) classification criteria for SLE , were positive for anti-double-str and ed DNA or antinuclear antibodies , and had a Safety of Estrogens in Lupus Erythematosus National Assessment -Systemic Lupus Erythematosus Disease Activity Index ( SELENA-SLEDAI ) score ≥6 at baseline , were r and omized to receive placebo or blisibimod for at least 24 weeks . Patient self-reported fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale , and disease activity was evaluated using Physician ’s Global Assessment , SELENA-SLEDAI , and British Isles Lupus Assessment Group Score . Statistically significant improvements in FACIT-Fatigue score were observed among individuals r and omized to blisibimod , especially in the 200 mg QW group where favorable effects on disease activity with blisibimod compared to placebo were observed as early as Week 8 . The mean improvement from baseline of 6.9 points at Week 24 , compared with 4.4 points with placebo , met the criteria for minimal clinical ly important improvement difference defined for patients with SLE . Despite concomitant improvements in FACIT-Fatigue , SLE Responder Index ( SRI ) and SLE biomarkers ( reported previously ) , FACIT-Fatigue score correlated only weakly with disease activity . While poor correlation between fatigue and disease activity is not new , the observation that correlation remains poor despite concurrent population improvements in disease and fatigue brings a new facet to our underst and ing of SLE OBJECTIVE To evaluate abatacept therapy in patients with non-life-threatening systemic lupus erythematosus ( SLE ) and polyarthritis , discoid lesions , or pleuritis and /or pericarditis . METHODS In a 12-month , multicenter , exploratory , phase IIb r and omized , double-blind , placebo-controlled trial , SLE patients with polyarthritis , discoid lesions , or pleuritis and /or pericarditis were r and omized at a ratio of 2:1 to receive abatacept ( ∼10 mg/kg of body weight ) or placebo . Prednisone ( 30 mg/day or equivalent ) was given for 1 month , and then the dosage was tapered . The primary end point was the proportion of patients with new flare ( adjudicated ) according to a score of A/B on the British Isles Lupus Assessment Group ( BILAG ) index after the start of the steroid taper . RESULTS A total of 118 patients were r and omized to receive abatacept and 57 to receive placebo . The baseline characteristics were similar in the 2 groups . The proportion of new BILAG A/B flares over 12 months was 79.7 % ( 95 % confidence interval [ 95 % CI ] 72.4 , 86.9 ) in the abatacept group and 82.5 % ( 95 % CI 72.6 , 92.3 ) in the placebo group ( treatment difference -3.5 [ 95 % CI -15.3 , 8.3 ] ) . Other prespecified flare end points were not met . In post hoc analyses , the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7 % ( 95 % CI 31.8 , 49.5 ) versus 54.4 % ( 95 % CI 41.5 , 67.3 ) , and the proportions with physician-assessed flare were 63.6 % ( 95 % CI 54.9 , 72.2 ) and 82.5 % ( 95 % CI 72.6 , 92.3 ) , respectively ; treatment differences were greatest in the polyarthritis group . Prespecified exploratory patient-reported outcomes ( Short Form 36 health survey , sleep problems , fatigue ) demonstrated a treatment effect with abatacept . The frequency of adverse events ( AEs ) was comparable in the abatacept and placebo groups ( 90.9 % versus 91.5 % ) , but serious AEs ( SAEs ) were higher in the abatacept group ( 19.8 versus 6.8 % ) . Most SAEs were single , disease-related events occurring during the first 6 months of the study ( including the steroid taper period ) . CONCLUSION Although the primary / secondary end points were not met in this study , improvements in certain exploratory measures suggest some abatacept efficacy in patients with non-life-threatening manifestations of SLE . The increased rate of SAEs requires further assessment Objective . The LupusPRO , a disease-targeted patient-reported outcome measure , was developed and vali date d in US patients with systemic lupus erythematosus ( SLE ) . We report the results of the cross-cultural validation study of the English version of the LupusPRO among patients in Canada with SLE . Method . The LupusPRO was administered to English-speaking Canadian patients with SLE . Demographic , clinical , and serological characteristics were obtained , and the Medical Outcomes Study Short Form-36 ( SF-36 ) and LupusPRO were administered . Disease activity was ascertained using the Safety of Estrogens in Lupus Erythematosus National Assessment -Systemic Lupus Erythematosus Disease Activity Index ( SELENA-SLEDAI ) and the Lupus Foundation of America definition of flare ( Yes/No ) . Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index ( SDI ) . Physician disease activity and damage assessment s were also ascertained using visual analog scales . A mail-back LupusPRO form was completed within 2–3 days of the index visit . Items tested were internal consistency reliability ( ICR ) , test-retest reliability ( TRT ) , convergent and discriminant validity ( against corresponding domains of the SF-36 ) , criterion validity ( against disease activity or health status ) , and known-groups validity . Results . Participants were 123 Canadian patients with SLE ( 94 % women ) ; mean age was 47.7 ( SD 14.8 ) years . The median ( interquartile range ) SELENA-SLEDAI and SDI were 4 ( 6 ) and 1 ( 3 ) , respectively . The ICR of the LupusPRO domains ranged from 0.60 to 0.93 , while the TRT range was 0.62–0.95 . Measures observed were convergent and discriminant validity with corresponding domains of SF-36 , criterion validity , and known-groups validity against disease activity , damage , and health status . Confirmatory factor analysis showed a good fit . Conclusion . The LupusPRO has fair psychometric properties among Canadian patients with SLE , and prospect i ve studies to establish minimally important difference are continuing OBJECTIVE To study prospect ively the effect of treatment with cyclophosphamide pulses ( CYC ) or azathioprine with methylprednisolone ( AZA ) , both for 24-month periods , on health-related quality of life ( HRQOL ) in patients with proliferative lupus nephritis ( LN ) in a r and omized controlled trial . We expected better HRQOL during AZA treatment . METHODS HRQOL and disease activity were measured at start and after 12 and 24 months . Generic question naires [ patient 's visual analog scale ( VAS ) , Medical Outcomes Study Short Form-36 Health Survey ( SF-36 ) , Profile of Mood States ] and a disease-specific measure [ Systemic Lupus Erythematosus ( SLE ) Symptom Checklist ] were used . Treatment burden was assessed at 24 months . Disease activity was measured with the SLE Disease Activity Index ( SLEDAI ) and physician 's VAS . RESULTS Complete question naire data were available from 47 of the 87 patients included in the trial . These patients were representative of the whole group , except that completers were more often Caucasian . HRQOL scores improved significantly during treatment , particularly during the first year , on both generic and disease-specific outcomes . No statistically significant differences were found in HRQOL between the CYC and AZA groups , except for the SF-36 mental component summary scale , which showed more favorable scores in the AZA group . The mean reported treatment burden at 24 months was significantly higher in the CYC group . HRQOL scores did not correlate with the SLEDAI and physician 's VAS . The disease activity measures correlated positively with each other . CONCLUSION Treatment of patients with proliferative LN with immunosuppressive drugs and corticosteroids improves HRQOL , particularly in the first year . Due to the small groups studied , the absence of differences between AZA and CYC for most HRQOL scales should be interpreted cautiously : our data suggest that there may be no significant differences . Differences were a higher perceived treatment burden and worse mental HRQOL in the CYC group Objective Dehydroepi and rosterone ( DHEA ) has been reported to improve fatigue and reduced well-being . Both are major problems in patients with systemic lupus erythematosus ( SLE ) , even with quiescent disease . Low serum DHEA levels are common in SLE . The present work investigates the effects of DHEA administration on fatigue , well-being and functioning in women with inactive SLE . Methods In a double-blind , r and omised , placebo-controlled study , 60 female patients with inactive SLE received 200 mg oral DHEA or placebo . Primary outcome measures were general fatigue , depressive mood , mental well-being and physical functioning . Assessment s were made before treatment , after 3 , 6 and 12 months on medication , and 6 months after cessation of treatment . Results Patients from the DHEA and placebo group improved on general fatigue ( p<0.001 ) and mental well-being ( p=0.04 ) . There was no differential effect of DHEA . The belief that DHEA had been used was a stronger predictor for improvement of general fatigue than the actual use of DHEA ( p=0.04 ) . Conclusions The trial does not indicate an effect of daily 200 mg oral DHEA on fatigue and well-being , and therefore DHEA treatment is not recommended in unselected female patients with quiescent SLE . Clinical Trials Registration Number In a 76-week , r and omized controlled trial , patients received 100 mg LJP 394 or placebo weekly for 16 weeks followed by three 12-week treatment cycles of 50 mg LJP 394 or placeboweekly each separated by eight-week periods when no therapy was administered . Health-related quality of life ( HRQOL ) was assessed using SF-36 at baseline , 16 weeks and every 12 weeks thereafter . Analyses population s included intent to treat ( ITT ) ( n 179 ) and patients with high-affinity anti-dsDNA antibody binding ( HA ) : 157/179 ; 85 % active , 90 % placebo . In the ITT population , there were improvements in role emotional ( RE ) ( 7.3 versus - 8.2 ) , social functioning ( SF ) ( 4.3 versus 0.7 ) , and role physical ( RP ) ( 11.3 versus 6.0 ) domains in the active treatment group when compared with placebo , with similar changes observed in the HA population . In 37 patients with data pre- and post-renal flares , those receiving LJP 394 reported stabilization or improvement in all but one domain compared with deterioration in all domains with placebo . Changes in RE domain scores following a flare differed by 22.7 points between the two treatment groups , favouring LJP 394 treatment . Patients receiving LJP 394 reported stable or improved HRQOL with active treatment following renal flares compared with deterioration in placebo . Differences between treatment groups in RE and SF domains are clinical ly important and were replicated irrespective of the protocol population analysed OBJECTIVE To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis . Secondary objectives included evaluation of the effect of abetimus on C3 levels , anti-double-str and ed DNA ( anti-dsDNA ) antibody levels , use of high-dose corticosteroids and /or cyclophosphamide , and major systemic lupus erythematosus ( SLE ) flare . METHODS We conducted a r and omized , placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients . Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels > 15 IU/ml were r and omized to a treatment group ( 158 abetimus , 159 placebo ) ; 298 ( 94 % ) were enrolled in the intent-to-treat ( ITT ) population ( 145 abetimus , 153 placebo ) , based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening . RESULTS Abetimus did not significantly prolong time to renal flare , time to initiation of high-dose corticosteroid and /or cyclophosphamide treatment , or time to major SLE flare . However , there were 25 % fewer renal flares in the abetimus group compared with the placebo group ( 17 of 145 abetimus-treated patients [ 12 % ] versus 24 of 153 placebo-treated patients [ 16 % ] ) . Abetimus treatment decreased anti-dsDNA antibody levels ( P < 0.0001 ) , and reductions in anti-dsDNA levels were associated with increases in C3 levels ( P < 0.0001 ) . More patients in the abetimus group experienced > or = 50 % reductions in proteinuria at 1 year , compared with the placebo group ( nominal P = 0.047 ) . Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline . Treatment with abetimus for up to 22 months was well tolerated . CONCLUSION Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo . Multiple positive trends in renal end points were observed in the abetimus treatment group OBJECTIVE Systemic lupus erythematosus ( SLE ) is a chronic systemic autoimmune disease characterized by a relapsing-remitting course . When a mild/moderate flare occurs , treatment with corticosteroids is often instituted . There are 2 methods of acutely giving a boost of steroids : triamcinolone injection or a short-term boost of oral prednisone or methylprednisolone . We investigated whether triamcinolone is superior to oral corticosteroids for mild/moderate flare in patients with lupus . METHODS In a clinical trial , 50 patients with SLE presenting with a mild or moderate flare [ defined using the Safety of Estrogens in Lupus Erythematosus : National Assessment -SLE Disease Activity Index ( SELENA-SLEDAI ) flare instrument ] were r and omized to receive oral methylprednisolone with rapid tapering ( medrol dose-pack ) or triamcinolone 100 mg , given intramuscularly . The patients completed a Likert scale of activity and the Medical Outcomes Study Short Form-36 health status question naire on the r and omization day , and repeated them the next day , 2 days , one week , 2 weeks , 3 weeks , and one month later . RESULTS Complete improvement occurred in 0 % at one day , 0 % at 2 days , 8.3 % at one week , 20.8 % at 2 weeks , 20.8 % at 3 weeks , and 25 % at 4 weeks in the methylprednisolone group versus 4.3 % at one day , 4.3 % at 2 days , 8.6 % at one week , 12.5 % at 2 weeks , 30.4 % at 3 weeks , and 34.7 % at 4 weeks in the triamcinolone group . Improvement in health status by Week 4 occurred in 66.6 % of the patients in the methylprednisolone group versus 73.9 % in the triamcinolone group . CONCLUSION The triamcinolone and oral methylprednisolone groups did equally well . Triamcinolone may lead to a more rapid response than the oral methylprednisolone ( 69.5 % vs 41.6 % with some improvement at day one ) The primary objective was to assess the long‐term safety of repeated courses of epratuzumab therapy in patients with moderate‐to‐severe systemic lupus erythematosus . Secondary objectives were to assess long‐term efficacy and health‐related quality of life ( HRQOL ) OBJECTIVE To determine whether low-dose ciclosporin was a more effective corticosteroid-sparing agent than AZA in patients with SLE . METHODS Patients with SLE requiring a change or initiation of a corticosteroid-sparing agent and who were taking > or = 15 mg of prednisolone/day were r and omized to receive either ciclosporin or AZA during this 12-month open-label multi-centre trial . There were strict guidelines for the reduction of prednisolone . The primary outcome was the absolute mean change in prednisolone . RESULTS Eighty-nine patients were r and omized . Using an intention-to-treat analysis , the absolute mean change in prednisolone dose between baseline and 12 months , adjusted for baseline prednisolone dose , was 9.0 mg for ciclosporin ( 95 % CI 7.2 , 10.8 ) and 10.7 mg for AZA ( 95 % CI 8.8 , 12.7 ) . The difference in the change between treatment groups was -1.7 mg ( 95 % CI -4.4 , 0.9 ; P = 0.2 ) . No significant differences were detected for the secondary outcomes : change in disease activity [ classic British Isles Lupus Assessment Group ( BILAG ) index ] , number of flares , development of new damage or change in quality of life . A similar number of patients in each arm stopped the study drugs due to adverse events and ineffectiveness . No patient developed severe hypertension or a persistent rise in creatinine . One patient in the ciclosporin arm developed a significant increase in proteinuria due to disease activity . CONCLUSIONS Both drugs were effective corticosteroid-sparing agents . Ciclosporin was not a more effective corticosteroid-sparing agent . Ciclosporin may be considered in patients who are unable to tolerate AZA . Patients on ciclosporin require close monitoring of blood pressure and creatinine . TRIAL REGISTRATION Current Controlled Trials , http://www.controlled-trials.com/ , IS RCT N35919612 |
10,356 | 26,467,494 | Our study indicated that IRT lowers SBP , DBP and MAP .
The magnitude of effect may be larger in hypertensive males aged ⩾45 years , using unilateral arm IRT for > 8 weeks | The objective of our study was to examine the effects of isometric resistance training ( IRT ) on resting blood pressure in adults . | Substantial progress has been made in the awareness , treatment , and prevention of cardiovascular disease ( CVD ) in women since the first women-specific clinical recommendations for the prevention of CVD were published by the American Heart Association ( AHA ) in 1999.1 The myth that heart disease is a “ man 's disease ” has been debunked ; the rate of public awareness of CVD as the leading cause of death among US women has increased from 30 % in 1997 to 54 % in 2009.2 The age-adjusted death rate result ing from coronary heart disease ( CHD ) in females , which accounts for about half of all CVD deaths in women , was 95.7 per 100 000 females in 2007 , a third of what it was in 1980.3,4 Approximately 50 % of this decline in CHD deaths has been attributed to reducing major risk factors and the other half to treatment of CHD including secondary preventive therapies.4 Major r and omized controlled clinical trials such as the Women 's Health Initiative have changed the practice of CVD prevention in women over the past decade.5 The investment in combating this major public health issue for women has been significant , as have the scientific and medical achievements . Despite the gains that have been made , considerable challenges remain . In 2007 , CVD still caused ≈1 death per minute among women in the United States.6 These represent 421 918 deaths , more women 's lives than were cl aim ed by cancer , chronic lower respiratory disease , Alzheimer disease , and accidents combined.6 Reversing a trend of the past 4 decades , CHD death rates in US women 35 to 54 years of age now actually appear to be increasing , likely because of the effects of the obesity epidemic.4 CVD rates in the United States are significantly higher for black females compared with their white counterparts ( 286.1/100 000 versus We reported previously that two otherwise identical training programs at lower ( LI ) and higher intensity ( HI ) similarly reduced resting systolic blood pressure ( BP ) by approximately 4 - 6 mmHg . Here , we determined the effects of both programs on BP-regulating mechanisms , on biomarkers of systemic inflammation and prothrombotic state and on the heart . In this cross-over study ( 3 × 10 weeks ) , healthy participants exercised three times 1 h/week at , respectively , 33 % and 66 % of the heart rate ( HR ) reserve , in a r and om order , with a sedentary period in between . Measurements , performed at baseline and at the end of each period , involved blood sampling , HR variability , systolic BP variability ( SBPV ) and cardiac magnetic resonance imaging . Thirty-nine participants ( 18 men ; mean age 59 years ) completed the study . Responses were not different between both programs ( P>0.05 ) . Pooled data from LI and HI showed a reduction in HR ( -4.3 ± 8.1 % ) and an increase in stroke volume ( + 11 ± 23.1 % ) . No significant effect was seen on SBPV , plasma renin activity , basal nitric oxide and left ventricular mass . Our results suggest that the BP reduction observed appears to be due to a decrease in systemic vascular resistance ; training intensity does not significantly affect the results on mechanisms , biomarkers and the heart Introduction : Several established tools are available to assess study quality and reporting of r and omized controlled trials ; however , these tools were design ed with clinical intervention trials in mind . In exercise training intervention trials some of the traditional study quality criteria , such as participant or research er blinding , are extremely difficult to implement . Methods : We developed the Tool for the assEssment of Study qualiTy and reporting in EXercise ( TESTEX ) – a study quality and reporting assessment tool , design ed specifically for use in exercise training studies . Our tool is a 15-point scale ( 5 points for study quality and 10 points for reporting ) and addresses previously unmentioned quality assessment criteria specific to exercise training studies . Results : There were no systematic differences between the summated TESTEX scores of each observer [ H(2 ) = 0.392 , P = 0.822 ] . There was a significant association between the summated TESTEX scores of the three observers , with almost perfect agreement between observers 1 and 2 [ intra-class correlation coefficient ( ICC ) = 0.93 , 95 % confidence interval ( CI ) 0.82–0.97 , P < 0.001 ] , observers 1 and 3 ( ICC = 0.96 , 95 % CI 0.89–0.98 , P < 0.001 ) and observers 2 and 3 ( ICC = 0.91 , 95 % CI 0.75–0.96 , P < 0.001 ) . Conclusions : The TESTEX scale is a new , reliable tool , specific to exercise scientists , that facilitates a comprehensive review of exercise training trials 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 No previous studies have examined the effects of isometric training intensity upon resting blood pressure ( BP ) . The aims of this study were ( a ) to compare the effects of leg isometric training , performed at two intensities , upon resting systolic-SBP , diastolic-DBP and mean arterial-MAP BP ; and ( b ) to examine selected cardiovascular variables , in an attempt to explain any changes in resting BP following training . Thirty-three participants were r and omly allocated to either control , high- ( HI ) or low-intensity ( LI ) training for 8 weeks . Participants performed 4 × 2 min exercise bouts 3 × weekly . Resting BP was measured at baseline , 4-weeks and post-training . SBP , DBP and MAP fell significantly in both groups after training . Changes were –5.2 ± 4.0 , –2.6 ± 2.9 and –2.5 ± 2.2 mmHg [ HI ] ; –3.7 ± 3.7 , –2.5 ± 4.8 and –2.6 ± 2.5 mmHg [ LI ] for SBP , DBP and MAP , respectively . There were no significant changes in BP at 4 weeks . No significant changes were observed in any of the other cardiovascular variables examined . These findings suggest that isometric training causes reductions in SBP , DBP and MAP at a range of exercise intensities , when it is performed over 8 weeks . Furthermore , it is possible to reduce resting BP using a much lower isometric exercise intensity than has previously been shown Objectives Isometric h and grip ( IHG ) training ( four , 2-min sustained contractions at 30 % of maximal voluntary contraction , three times per week for 8–10 weeks ) lowers resting arterial blood pressure ( BP ) in hypertensive patients , including those receiving pharmacotherapy , although the mechanisms remain elusive . Ambulatory BP measurements are more efficacious in predicting cardiovascular disease-related events , yet the effects of IHG training on ambulatory BP are unknown . The objective of the current investigation was to test the hypotheses that 8 weeks of IHG training lowers resting and 24 h ambulatory BP concomitantly in medicated hypertensive patients , and may be the result of improved vagal modulation . Methods BP was assessed using brachial artery oscillometry , and coarse-graining spectral analysis was used to determine spectral power . Resting and 24 h ambulatory BP and heart rate variability ( HRV ) were measured pretraining , midtraining , and post-training in 11 medicated hypertensive patients ( mean±SD , resting BP : 113.9±12.7/60.7±11.6 mmHg ) , and in nine medicated hypertensive controls ( resting BP : 117.8±14.3/67.5±4.2 mmHg ) . Results Indices of BP and HRV were not significantly altered with IHG training ( all P>0.05 ) . Conclusion IHG training does not lower resting or ambulatory BP in hypertensive patients successfully treated with pharmacotherapy to within the normal range ( ⩽120/80 mmHg ) , nor does it improve HRV . Future studies should examine alternative IHG training protocol s in well-managed hypertensive patients and /or target poorly controlled medicated hypertensive patients Abstract To reduce resting blood pressure , a minimum isometric exercise training ( IET ) intensity has been suggested , but this is not known for short-term IET programmes . We therefore compared the effects of moderate- and low-intensity IET programmes on resting blood pressure . Forty normotensive participants ( 22.3 ± 3.4 years ; 69.5 ± 15.5 kg ; 170.2 ± 8.7 cm ) were r and omly assigned to groups of differing training intensities [ 20%EMGpeak ( ~23%MVC , maximum voluntary contraction , or 30%EMGpeak ( ~34%MVC ) ] or control group ; 3 weeks of IET at 30%EMGpeak result ed in significant reductions in resting mean arterial pressure ( e.g. −3.9 ± 1.0 mmHg , P < 0.001 ) , whereas 20%EMGpeak did not ( −2.3 ± 2.9 mmHg ; P > 0.05 ) . Moreover , after pooling all female versus male participants , IET induced a 6.9-mmHg reduction in systolic blood pressure in female participants , but only a 1.5-mmHg reduction in systolic blood pressure in male participants , although the difference was not significant . An IET intensity between 20%EMGpeak and 30%EMGpeak is sufficient to elicit significant resting blood pressure reductions in a short-term training period ( 3 weeks ) . In addition , sexual dimorphism may exist in the magnitude of reductions , but further work is required to confirm this possibility , which could be important in underst and ing the mechanisms responsible PURPOSE Research has demonstrated the efficacy of isometric h and grip ( IHG ) training to attenuate resting blood pressure . These studies have relied on the use of programmable digital h and grips for training . This study aim ed to determine the effectiveness of simple , inexpensive spring-loaded h and grip devices in producing hypotensive effects . METHODS The study was a r and omized controlled trial of 49 normotensive participants ( 66.4 ± 0.9 years ; 57 % women ) . Participants in the exercise group ( n = 25 ) trained and had blood pressure measured twice weekly for 8 weeks . Control participants ( n = 24 ) completed weekly blood pressure measurements . Pre- and posttraining measurements were each assessed over 3 visits . Statistical analysis of the pre-post data involved analyses of variance and hierarchical linear modeling was used to examine changes over time . RESULTS Following 8 weeks , IHG participants demonstrated significant reductions in resting blood pressure . Systolic and diastolic blood pressures were reduced from 122 ± 3 mm Hg to 112 ± 3 mm Hg ( P < .001 ) and from 70 ± 1 mm Hg to 67 ± 1 mm Hg ( P < .05 ) , respectively . Hierarchical linear modeling analysis also revealed a significant cross-level ( ie , group ÷ time ) interaction , with an estimated reduction in systolic blood pressure of 5.4 mm Hg ( P < .001 ) over the training period in the IHG group . CONCLUSIONS In agreement with previous studies , IHG training reduced resting arterial pressure following 8 weeks of training . Hypotensive effects linked to IHG training may be achieved using simple , inexpensive spring h and grip training devices and may provide a convenient and affordable therapeutic alternative or adjunctive therapy for lowering blood pressure PURPOSE This study examined the effects of isometric h and grip training on resting arterial blood pressure , heart rate variability , and blood pressure variability in older adults with hypertension . METHODS Nine subjects performed four 2-min isometric h and grip contractions at 30 % of the maximum voluntary contraction force , 3 d.wk(-1 ) for 10 wk , and eight subjects served as controls . RESULTS After training , there was a significant reduction in resting systolic pressure and mean arterial pressure . In addition , power spectral analysis of heart rate variability demonstrated that the low frequency : high frequency area ratio tended to decrease . CONCLUSIONS It is concluded that isometric training at a moderate intensity elicits a hypotensive response and a simultaneous increase in vagal modulation in older adults with hypertension Abstract In this study , we examined the correlations between selected markers of isometric training intensity and subsequent reductions in resting blood pressure . Thirteen participants performed a discontinuous incremental isometric exercise test to volitional exhaustion at which point mean torque for the final 2-min stage ( 2min-torquepeak ) and peak heart rate peak ( HRpeak ) were identified . Also , during 4 weeks of training ( 3 sessions per week , comprising 4 × 2 min bilateral leg isometric exercise at 95 % HRpeak ) , heart rate ( HRtrain ) , torque ( Torquetrain ) , and changes in EMG amplitude ( ΔEMGamp ) and frequency ( ΔEMGfreq ) were determined . The markers of training intensity were : Torquetrain relative to the 2min-torquepeak ( % 2min-torquepeak ) , EMG relative to EMGpeak ( % EMGpeak ) , HRtrain ΔEMGamp , ΔEMGfreq , and % MVC . Mean systolic ( −4.9 mmHg ) and arterial blood pressure ( −2.7mmHg ) reductions correlated with % 2min-torquepeak ( r = −0.65 , P = 0.02 and r = −0.59 , P = 0.03 ) , ΔEMGamp ( r = 0.66 , P = 0.01 and r = 0.59 , P = 0.03 ) , ΔEMGfreq ( r = −0.67 , P = 0.01 and r = −0.64 , P = 0.02 ) , and % EMGpeak ( systolic blood pressure only ; r = −0.63 , P = 0.02 ) . These markers best reflect the association between isometric training intensity and reduction in resting blood pressure observed after bilateral leg isometric exercise training |
10,357 | 27,412,362 | Neonatal adverse effects were not assessed in any of the included studies .Comparisons of different NSAIDs and different doses of the same NSAID did not demonstrate any differences in their effectiveness on any of the primary outcome measures ; however , few data were available on some NSAIDs .
In women who are not breastfeeding and who sustained perineal trauma , NSAIDs ( compared to placebo ) provide greater pain relief for acute postpartum perineal pain and fewer women need additional analgesia when treated with a NSAID . | BACKGROUND Many women experience perineal pain after childbirth , especially after having sustained perineal trauma .
Perineal pain-management strategies are thus an important part of postnatal care .
Non-steroidal anti-inflammatory drugs ( NSAIDs ) are a commonly used type of medication in the management of postpartum pain and their effectiveness and safety should be assessed .
OBJECTIVES To determine the effectiveness of a single dose of an oral NSAID for relief of acute perineal pain in the early postpartum period . | Summary In a bid to minimise dosage and possible side-effects when relieving post episiotomy pain , the NSAID Indomethacin was studied in combination with a systemic haemostat Ethamsylate which has been shown to selectively inhibit some prostagl and ins . Comparative groups also took Indomethacin alone and placebo in a double blind non-crossover comparison . Efficacy was judged in terms of side-effects and assessment s of pain intensity , pain relief and global assessment of pain . There was some evidence of a beneficial interaction between Indomethacin and Ethamsylate when adjustments were made for the patient ’s age and initial pain score . Side-effects were most common in the combination therapy group Meclofenamate sodium , a nonsteroidal anti-inflammatory drug with proven analgesic effects , was compared at two dose levels ( 200 mg and 100 mg ) with codeine ( 60 mg ) and placebo in a double-blind , r and omized study of 327 women experiencing episiotomy pain after normal delivery . Meclofenamate sodium at either dose was significantly better than codeine or placebo in reducing pain intensity and increasing pain relief , and it had a longer duration of action . Adverse effects were minimal , and their frequency did not differ significantly among treatment groups . Meclofenamate sodium appears to be as safe as and more effective than codeine for the management of episiotomy pain OBJECTIVE The study was carried out to compare the analgesic effect of diclofenac sodium and indomethacin suppositories for management of right mediolateral episiotomy repair . METHOD A total of 70 patients who gave birth vaginally with right mediolateral episitomy were r and omly assigned to receive 100 mg diclofenac sodium suppositories/day ( G1 , n = 35 ) or 100 mg indomethacin supposotories/day ( G2 , n = 35 ) after episiotomy repair and postpartum for three days . Pain ratings were recorded before , the first hour and 24 hours after medication . The verbal rating scale ( VRS ) and visual analog scale ( VAS ) were used for pain recording . The independent T test , Mann-Whitney U and Wilcoxon rank test were used for statistical analysis and Spearman correlation analysis was used for comparison between VRS and VAS . RESULTS Diclofenac sodium was a more effective analgesic than indomethacin suppositories for right mediolateral episiotomy pain . For G1 the first hour VRS was 2.6 + /- 0.5 points and VAS 4.9 + /- 0.8 points ; for G2 the first hour VRS was 3.4 + /- 0.6 points VAS 6.6 + /- 1.2 points ; this difference was statistically significant ( p < 0.05 , Mann-Whitney U test ) . For G1 at the 24th hour VRS was 1.2 + /- 0.4 points and VAS 2.4 + /- 0.9 points ; for G2 at the 24th hour VRS was 2 + /- 0.7 points and VAS was 3.4 + /- 1.3 points ; the difference was statistically significant ( p < 0.05 , Mann-Whitney U test ) . The first and 24th hour pain scores ( VAS1-VAS24 , VRS1-VRS24 ) were decreased dramatically for both groups ( p < 0.05 , Wilcoxon rank test ) . A positive correlation was obtained between the first and 24th hour VRS and VAS by Spearman correlation analysis ( r(s ) = 0.9 , n = 70 , p = 0.000 ) . CONCLUSION The two analgesics were effective after episiotomy repair , however diclofenac sodium suppositories may be the preferred choice because they were more effective One hundred and ten patients who had episiotomies to aid normal vaginal delivery without epidural analgesia were = allocated at r and om to receive either diclofenac ( n = 56 ) or = placebo ( n = 54 ) suppositories . Pain after episiotomy was assessed at 24 and 48 hours using a combination of a visual analogue scale , a modified pain score and a review of additional analgesia required . All patients in both groups were allowed routine hospital analgesia on request . Our data suggests that very few patients suffered severe pain , even in the placebo group . However , the prophylactic use of diclofenac suppositories significantly reduced perineal pain in the first 24 hours , although the difference was less marked by 48 hours . Overall additional analgesia requirement was correspondingly less in the diclofenac group Objective To determine if diclofenac suppositories administered prophylactically produce effective A double-blind , placebo-controlled trial was carried out in 299 patients suffering from post-episiotomy pain to compare the analgesic effectiveness and tolerance of single doses of 500 mg dipyrone and 500 mg paracetamol . Assessment s of pain relief over a 6-hour period showed that dipyrone produced significantly better results than placebo within half an hour of intake and maintained this superiority throughout the 6 hours . It also afforded consistently better pain relief than paracetamol and was significantly more effective at the 6-hour assessment . Side-effects were few and mild Background : Pain is a worldwide problem that often originates from disease process , and diagnostic and treatment procedures such as surgical operations . Objectives : This trial was performed to compare the effectiveness of two analgesics for the management of perineal pain caused by episiotomy . Material s and Methods : A total of 170 nulliparous women who gave birth vaginally with episiotomy between March 2009 and November 2010 were r and omly assigned to receive either ibuprofen or celecoxib which were given orally every 6 or 12 hours , respectively . Pain levels were measured before the intervention , and at 1 , 2 , 4 , 8 and 12 hours after providing the first dose on a 10-cm visual analogue scale . Results : The results showed that the two groups had no significant differences regarding demographic characteristics , maternal , neonatal , and post-delivery factors , and mean premedication pain severity . Means of pain severity were different between the two groups as patients in the celecoxib group had lower means than the other group at 1,2,4,8 and 12 hours ( 4.01 ± 1.8 vs. 4.46 ± 1.9 , 3.17 ± 1.9 vs. 3.79 ± 1.7 , 2.89 ± 1.3 vs. 2.96 ± 1.5 , 2.19 ± 1.8 vs. 2.55 ± 1.4 , and 1.98 ± 1.1 vs. 2.45 ± 1.2 , respectively ) after administration of analgesics . Conclusions : Patients who received celecoxib had lower VAS in comparison with others . Although these differences were not significant , as celecoxib has longer half-life , fewer upper GI symptoms , and is better tolerated based on the previous studies , and this study is in favor of using it OBJECTIVES To evaluate efficacy of ibuprofen compared with acetaminophen for relief of perineal pain after childbirth , side effects of ibuprofen compared with acetaminophen and patient satisfaction in treatment between the 2 groups . MATERIAL AND METHOD A total of 210 women who gave birth by spontaneous vaginal delivery with mediolateral episiotomy between June 2006 and November 2006 were r and omly assigned to receive either ibuprofen ( 400 mg ) ( n = 106 ) or acetaminophen ( 1000 mg ) ( n = 104 ) , both given orally when suturing was completed . Pain ratings were recorded before the treatment and at 1 , 2 , 3 and 4 hours after the treatment on a 10-cm visual analogue scale . Side effects and patient satisfaction were assessed at 24 hours . RESULTS Pain in the ibuprofen group was considerably more reduced than the acetaminophen group at 1 hour of treatment ( mean pain rating 2.18 vs. 2.88 , respectively ; p < 0.003 ) . Even though , at 2 , 3 and 4 hours of treatment ibuprofen seemed to give more reliefof pain than acetaminophen , they did not reach statistically significant differences ( mean pain rating ; at 2 hour : 1.59 vs. 1.97 , p = 0.093 ; at 3 hour : 1.08 vs. 1.31 , p = 0.183 ; and at 4 hour : 0.69 vs. 0.85 , p = 0.169 ; respectively ) . There were no side effects and no significant differences in overall patient satisfaction between the two groups . CONCLUSION Ibuprofen was consistently better than acetaminophen at 1 hour after treatment for relief of perineal pain after childbirth without any side effects . After 2 hours , ibuprofen and acetaminophen had similar analgesic properties Our purpose was to evaluate the analgesic efficacy of single oral doses of ketoprofen 25 , 50 , and 100 mg compared with aspirin 650 mg and placebo in the relief of moderate to severe postepisiotomy , uterine cramping , or cesarean section pain . One hundred and fifty-six patients participated in a r and omized , double-blind , stratified , parallel-group study . They were observed over a six-hour period by one nurse-observer . Several of the st and ard summary measures of analgesia were derived from the interview data , including the sum of pain intensity differences ( SPID ) and the sum of the hourly relief values ( TOTAL ) . The study showed significant differences between aspirin and placebo for four-hour SPID and several other parameters and between ketoprofen at all dose levels and placebo for the four- and six-hour SPID and many other parameters . The two higher doses of ketoprofen were significantly more effective than aspirin as as assessed by the four- and six-hour SPID , TOTAL , and other summary measures . The low dose of ketoprofen , although not significantly different from aspirin for SPID and TOTAL , showed a significantly faster onset of relief and had a better global rating . This study suggests that 50 mg of ketoprofen may be the clinical dose of choice as an analgesic . There were no adverse effects reported The analgesic activity of 300 and 600 mg . of flufenisal , a fluorinated phenyl derivative of aspirin , was compared to 600 and 1,200 mg . of aspirin and to placebo under r and omized double‐blind conditions in 100 patients with pain due to episiotomy . Over the 8 hours of evaluation , pain reduction greater than 50 per cent was observed in at least 60 per cent of patients treated with both doses of flufenisal , whereas it was 40 per cent with 600 mg . of aspirin , 55 per cent with 1,200 mg . of aspirin , and 26 per cent with placebo . On a time‐effect basis with the two grade d doses of both flufenisal and aspirin , pain relief , as measured by pain intensity differences , was similar with respect to time of onset and maximal effect attained . However , with the flufenisal significant analgesia persisted at the eighth hour ( p < 0.02 ) , while with the aspirin there was none after the fifth hour . On the basis of these data , flufenisal at one fourth to one half the dose of aspirin appears to provide analgesia of almost double the duration of aspirin and is equivalent to aspirin in time of onset and degree of relief of episiotomy pain . This raises the possibility that in some clinical conditions flufenisal may be effective in providing prolonged pain relief A double-blind , r and omised placebo-controlled study was carried out to assess the efficacy of indometacin suppositories as a post-episiotomy analgesic . Thirty patients received 2 X 100 mg indometacin suppositories , and 30 patients received placebo suppositories within 15 min of an episiotomy repair operation . Local infiltration of the episiotomy incision was performed using 20 ml of 0.5 % lignocaine in every case . Subjective symptoms of pain were evaluated 15 , 30 , 60 and 90 min post-episiotomy repair . Average numbers of hours as lying in patients after delivery is 4 h. None of the patients who received indometacin complained of post-episiotomy pain ; whereas the patients on placebo manifested varying degrees of pain To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral ( ARV ) regimens for the prevention of mother-to-child transmission ( MTCT ) of human immunodeficiency virus ( HIV ) type 1 during labor and delivery , HIV-infected pregnant women were screened at 11 maternity health institutions in South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine ( Nvp ) or multiple-dose zidovudine and lamivudine ( Zdv/3TC ) . The overall estimated HIV-1 infection rates in 1307 infants by 8 weeks were 12.3 % ( 95 % confidence interval [ CI ] , 9.7 - 15.0 ) for Nvp and 9.3 % ( 95 % CI , 7.0 - 11.6 ) for Zdv/3TC ( P=.11 ) . Excluding infections detected within 72 h ( intrauterine ) , new HIV-1 infections were detected in 5.7 % ( 95 % CI , 3.7 - 7.8 ) and 3.6 % ( 95 % CI , 2.0 - 5.3 ) of infants in the Nvp and Zdv/3TC groups , respectively , in the 8 weeks after birth . There were no drug-related maternal or pediatric serious adverse events . Common complications were obstetrical for mothers ( Nvp group , 24.3 % ; Zdv/3TC group , 26.3 % ) and respiratory for infants ( Nvp group , 16.1 % ; Zdv/3TC group , 17.0 % ) . This study further confirms the efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form BACKGROUND Pain from episiotomy or tearing of perineal tissues during childbirth is often poorly treated and may be severe . This r and omized double-blind controlled trial was performed to compare the effectiveness , side effects and cost of , and patient preference for , 2 analgesics for the management of postpartum perineal pain . METHODS A total of 237 women who gave birth vaginally with episiotomy or a third- or fourth-degree tear between August 1995 and November 1996 at a tertiary-level teaching and referral centre for obstetric care in Vancouver were r and omly assigned to receive either ibuprofen ( 400 mg ) ( n = 127 ) or acetaminophen ( 600 mg ) with codeine ( 60 mg ) and caffeine ( 15 mg ) ( Tylenol No. 3 ) ( n = 110 ) , both given orally every 4 hours as necessary . Pain ratings were recorded before the first dose and at 1 , 2 , 3 , 4 , 12 and 24 hours after the first dose on a 10-cm visual analogue scale . Side effects and overall opinion were assessed at 24 hours . RESULTS Ibuprofen and acetaminophen with codeine had similar analgesic properties in the first 24 hours post partum ( mean pain rating 3.4 and 3.3 , mean number of doses in 24 hours 3.4 and 3.3 , and proportion of treatment failures 13.8 % [ 16/116 ] and 16.0 % [ 16/100 ] respectively ) . Significantly fewer subjects in the ibuprofen group than in the acetaminophen with codeine group experienced side effects ( 52.4 % v. 71.7 % ) ( p = 0.006 ) . There were no significant differences in overall patient satisfaction between the 2 groups . The major determinant of pain intensity was forceps-assisted delivery . Overall , 78 % of the treatment failures were in women with forceps-assisted deliveries . INTERPRETATION Since the 2 analgesics were rated similarly , ibuprofen may be the preferred choice because it is less expensive and requires less nursing time to dispense . Further studies need to address improved analgesia for women with forceps-assisted deliveries This study was conducted to compare the analgesic action of Lysine Clonixinate ( LC ) vs Paracetamol/Codeine association ( PC ) in the treatment of postepisiotomy pain in primiparae women : 131 primiparous patients with moderate-to-severe postepisiotomy pain were enrolled in a double blind dummy design study and r and omly allocated to either treatment with fixed doses of LC 125 mg or Paracetamol 500 mg+Codeine 30 mg 6 qh during 24 hours . Intensity of spontaneous pain and pain on walking was assessed according to a visual analog scale ( VAS ) and patient 's assessment before receiving treatment and after 1 , 2 , 6 and 24 hours . Intensity of spontaneous pain was reduced in 24 hours from 4.28 + /- 2.11 to 1.73 + /- 1.46 ( P < 0.0001 ) in the LC group and from 4.78 + /- 2.08 to 1.90 + /- 1.72 in the PC-treated group ( p < 0.0001 ) ; with no significant differences between treatments . 54 % of the patients treated with LC and 55 % of those receiving PC showed onset of analgesic action 30 minutes following dose administration . Patient 's final global assessment revealed that 95 % of LC-treated patients and 96 % of the PC group showed total or partial pain relief during the first treatment day . No sleep disturbances were seen during the night in 75 % of patients . Only one patient receiving LC showed nausea not requiring treatment discontinuation . It is concluded that both treatments are equally effective to relieve moderate-to-severe postepisiotomy pain & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data A double-blind , placebo-controlled , parallel group study was performed to compare the analgesic efficacy of diclofenac potassium ( 25 , 50 , or 100 mg ) with that of aspirin ( 650 mg ) , or placebo . Two hundred fifty-five in patients with severe postepisiotomy pain were r and omly assigned to receive a single oral dose of one of the four active treatments or placebo . Analgesia was assessed over an 8-hour period . Treatments were compared on the basis of st and ard scales for pain intensity and relief and a number of derived variables based on these data , as well as two global ratings of the study medication . All active treatments were effective analgesics statistically superior to placebo for many hourly and summary measures , including the global ratings . Diclofenac potassium ( 50 and 100 mg ) was statistically significantly superior to aspirin at half-hour and for many other hourly scores from hour 3 on . The 4− and 8-hour sum of the pain intensity difference and total pain relief scores reflected the superiority of diclofenac potassium to aspirin . In addition , the 100-mg dose was significantly more efficacious than the 25-mg dose of diclofenac potassium . The probability of obtaining onset was significantly better for all active treatments than for placebo ; however , the median onset times were similar for all treatments . The duration of effect , as measured by mean pain intensity difference and relief scores , was better for diclofenac potassium than aspirin , and these differences were significant for the 50− and 100-mg doses . The probability of pain returning to baseline was significantly less for the diclofenac groups than for placebo or aspirin groups . In addition , significantly fewer patients treated with diclofenac ( 25 , 50 , or 100 mg ) or aspirin ( 650 mg ) required remedication during the 8-hour study period as compared with those treated with placebo . Diclofenac potassium is an effective analgesic in the range of aspirin ( 650 mg ) at the 25-mg dose and superior in efficacy and longer lasting than aspirin at the 50− and 100-mg doses . The onset of analgesia was similar for aspirin and diclofenac potassium A single-dose , double-blind , r and omized clinical trial was conducted to examine the relative analgesic efficacy of ibuprofen 400 mg ( n = 36 ) , acetaminophen 1000 mg ( n = 37 ) , and placebo ( n = 38 ) in postpartum patients who had moderate to severe pain after episiotomy . At regular intervals over 4 hours , patients evaluated pain severity and relief on categorical scales and completed a categorical overall evaluation at the end of the trial . Both active agents were effective compared with placebo ( P less than .05 ) . Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for the sum of pain intensity difference , total pain relief , and reduction of pain by more than 50 % ( P less than .05 ) , suggesting a more rapid onset of action and a more prolonged effect by ibuprofen 400 mg . No adverse effects were reported . Based on the results of this conventional postpartum episiotomy pain model , both agents are considered efficacious and ibuprofen 400 mg is a more effective analgesic for the relief of acute pain than acetaminophen 1000 mg OBJECTIVE Postpartum perineal pain and dyspareunia have been reported to affect 42 % of women within the first 2 weeks after their first vaginal delivery . We aim ed to determine the prevalence of dyspareunia and perineal pain using vali date d pain scores following accurate classification of perineal trauma according to the guidelines of the Royal College of Obstetricians and Gynaecologists . STUDY DESIGN Prospect i ve study of women having their first vaginal delivery . All women had a perineal and rectal examination . Pain was assessed with a 4-point Verbal Rating Score and an 11-point visual analogue scale on day 1 , day 5 and 2 months after delivery . RESULTS Two hundred and fifty-four women were invited and 95 % participated . Ninety-two percent experienced perineal pain on day one , resolving in 88 % ( p<0.001 ) at 2 months . Compared to an intact perineum or first degree tear significantly more women experienced perineal pain after a second , third or fourth degree tear . Forty percent resumed coitus within 2 months regardless of whether perineal trauma occurred or not . Five days after delivery , uncomplicated episiotomies result ed in more perineal pain than second degree tears . CONCLUSIONS Although perineal pain affected 92 % of mothers , it resolved in the majority within 2 months of delivery . Obstetric anal sphincter injury is associated with more perineal pain than other perineal trauma . Spontaneous second degree tears cause less perineal pain than episiotomies . The 11-point visual analogue scale may be more sensitive than the 4-point Verbal Rating Score OBJECTIVES The purpose of this study was to determine the frequency of perineal pain in the 6 weeks after vaginal delivery and to assess the association between perineal trauma and perineal pain . Study design This was a prospect i ve cohort study of parturients at 1 day , 7 days , ' and 6 weeks ' post partum in an academic tertiary obstetric unit in Toronto , Canada . Four hundred forty-four women were followed up , including women with an intact perineum ( n=84 ) , first-/second-degree tears ( n=220 ) , episiotomies ( n=97 ) , or third-/fourth-degree tears ( n=46 ) . Primary outcome was the incidence of perineal pain on day of interview ; secondary outcomes were pain score measurements and interference with daily activities . RESULTS Perineal trauma was more common among primiparous women , those with operative vaginal deliveries , and those with epidural analgesia during the second stage of labor . The incidence of perineal pain among the groups during the first week was intact perineum 75 % ( day 1 ) and 38 % ( day 7 ) ; first-/second-degree tears 95 % and 60 % ; episiotomies 97 % and 71 % ; and third-/fourth-degree tears 100 % and 91 % . By 6 weeks , the frequency of perineal pain was not statistically different between trauma groups . CONCLUSION Acute postpartum perineal pain is common among all women . However , perineal pain was more frequent and severe for women with increased perineal trauma Chlorphenesin carbamate , a compound structurally related to mephenesin , is a new skeletal muscle relaxant . In trials"3 involving patients with a variety of painful conditions associated with muscle spasm , mainly arthritis , chlorphenesin was reported eff ective in relieving pain . It was not clear , however , whether the pain-relieving effect of chlorphenesin in these patients was due to a muscle relaxant or to direct analgesic effect of this drug . The purpose of the present study was to determine if chlorphenesin possesses analgesic activity independent of a muscle-relaxant property . The analgesic effects of this drug were evaluated in patients with postepisiotomy pain under controlled conditions ; two doses of chlorphenesin and a combination of chlorphenesin with acetylsalicylic acid ( ASA ) were compared to ASA alone and to a placebo Summary A double-blind single-dose comparison was performed comparing the analgesic effects of ibuprofen ( ‘ Brufen ’ ) 400 mg . and dextropropoxyphene 65 mg . The women who were admitted to the trial were those who , following full-term vaginal delivery , required an analgesic agent for control of their pain . Pain relief was measured , half hourly for two hours , then hourly for the next ten hours , on a five point scale ranging from no relief to complete relief of pain . † ‘ Brufen ’ is the Boots trade name for ibuprofen . Statistical analysis of the results using the Mann-Whitney U Test showed the analgesic effect of ibuprofen to be superior to that of dextropropoxyphene at the one hour , one and a half hour , four hour and five hour recordings at the 5 % level of probability , and over the total 12 hour period at the 0.1 % level of probability . Side-effects were noted in only one case , this being a patient who had an allergic-like response to ibuprofen Summary . In a single‐dose , r and omized . double‐blind study of 100 women , suprofen and dihydrocodeine were compared in the relief of pain after episiotomy . The drugs were equal in terms of analgesic efficacy , duration of analgesia and onset of action . Neither drug demonstrated any serious adverse effects Abstract In this study , we compare the prophylactic efficacy of a diclofenac suppository and an indomethacin suppository on decreasing post-episiotomy pain . A total of 90 women with 2nd-degree episiotomy were assigned to receive a single dose of diclofenac suppository ( 30 ) , indomethacin suppository ( 30 ) or placebo ( 30 ) , according to r and omised blocks . The pain was assessed at 1 , 2 , 4 , 6 and 12 hours after receiving analgesia , using the two methods of pain score and visual analogue . This study showed that in the group given diclofenac or indomethacin , at all the assessed hours , the pain measured was considerably less than in the suppository-free group ( p < 0.05 ) . Comparing the diclofenac and indomethacin groups , there were only significant differences in the 4 and 12 hour measurements : the diclofenac was more effective than the indomethacin ( 4th hour ) , but due to a shorter half-life , the diclofenac group in the 12th hour had more pain ( p < 0.05 ) . Diclofenac suppository is recommended at 4-hour intervals for all patients , without internal disorders , to decrease episiotomy pain Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone , codeine sulfate 60 mg alone , and placebo . One hundred ninety‐five patients with severe pain result ing from episiotomy , cesarean section , or gynecologic surgery completed a r and omized , double‐blind , stratified , parallel‐group study . Patients were observed during a 4‐hour period after medication . Based on the sum of the pain intensity differences ( SPID ) , total pain relief ( TOTPAR ) , and most of the hourly direct measures of pain and relief , both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo . Codeine 60 mg was statistically superior to placebo based on TOTPAR , the global ratings , and a few hourly measures . The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone ½ , 1 , and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID , TOTPAR , and other measures as well . The low‐dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg . Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg , particularly in the first few hours after medication , is more efficacious than its constituents BACKGROUND Perineal pain is common after childbirth . We studied the effect of genital tract trauma , labor care , and birth variables on the incidence of pain in a population of healthy women exposed to low rates of episiotomy and operative vaginal delivery . METHODS A prospect i ve study of genital trauma at birth and assessment of postpartum perineal pain and analgesic use was conducted in 565 midwifery patients . Perineal pain was assessed using the present pain intensity ( PPI ) and visual analog scale ( VAS ) components of the vali date d short-form McGill pain scale . Multivariate logistic regression examined which patient characteristics or labor care measures were significant determinants of perineal pain and use of analgesic medicines . RESULTS At hospital discharge , women with major trauma reported higher VAS pain scores ( 2.16 + /- 1.61 vs 1.48 + /- 1.40 ; p < 0.001 ) and were more likely to use analgesic medicines ( 76.3 vs 23.7 % , p = 0.002 ) than women with minor or no trauma . By 3 months , average VAS scores were low in each group and not significantly different . Perineal pain at the time of discharge was associated in univariate analysis with higher education level , ethnicity ( non-Hispanic white ) , nulliparity , and longer length of active maternal pushing efforts . In a multivariate model , only trauma group and length of active pushing predicted the pain at hospital discharge . In women with minor or no trauma , only length of the active part of second stage labor had a positive relationship with pain . In women with major trauma , the length of active second stage labor had no independent effect on the level of pain at discharge beyond its effect on the incidence of major trauma . CONCLUSIONS Women with spontaneous perineal trauma reported very low rates of postpartum perineal pain . Women with major trauma reported increased perineal pain compared with women who had no or minor trauma ; however , by 3 months postpartum this difference was no longer present . In women with minor or no perineal trauma , a longer period of active pushing was associated with increased perineal pain In a double-blind single-dose study , the analgesic effect of a new ibuprofen-codeine phosphate combination was compared with those of codeine phosphate alone and placebo for the relief of moderate and severe postepisiotomy pain . In the 113 patients studied , combination therapy was superior to codeine phosphate alone and to placebo , the difference between the combination and codeine phosphate alone reaching statistical significance ( P less than 0.05 ) after two hours . The few side effects reported were not of a serious nature An on-going double-blind study was carried out in women requiring pain relief after episiotomy to compare the efficacy of 500 mg diflunisal twice daily , 65 mg dextropropoxyphene plus 650 mg paracetamol 3-times daily , and placebo . Fifty-seven patients , allocated at r and om to receive 2-days ' treatment with one or other of the trial drugs , have been studied to date . The preliminary results , as assessed by descriptive rating scales , showed that all three treatments were equally effective in relieving spontaneous pain and pain at night . Patients ' overall opinion showed no difference between treatments although the investigator assessed diflunisal to be better than the combined preparation and both to be better than placebo . A visual analogue scale of assessment is to be used for the remainder of the trial In a double-blind , single-dose study , the analgesic effect of a combined ibuprofen-codeine phosphate preparation was compared with those of zomepirac and placebo in 127 patients with moderate or severe postepisiotomy pain . Both the combination and zomepirac were significantly more effective than placebo for up to six hours , but the onset of action of the combination was more rapid than that of zomepirac . The study was notable for the virtual absence of side effects The analgesic efficacy and safety of a single oral dose of 100 mg of aceclofenac was compared in a double-blind study with a single dose of 650 mg of paracetamol in patients with severe episiotomal pain . The patients were question ed after 30 min and then at hourly intervals for 6 h after medication . A st and ard format ( Huskisson 's test ) was used to investigate the intensity of the pain throughout the study . The statistically significant results show that the analgesic effect of aceclofenac is superior to that of paracetamol . The tolerance of both compounds is excellent To evaluate relative efficacy , safety , and time course of analgesia , nefopam ( 45 and 90 mg ) , a new central ly acting nonnarcotic analgesic , was compared with propoxyphene ( 65 mg ) and placebo in a single oral dose , parallel , stratified , r and omized , double‐blind trial with 100 hospitalized postpartum women with medium or severe episiotomy pain . Using subjective reports as indices of response , patients rated pain intensity and side effects at periodic interviews for 6 hr . After 45 and 90 mg nefopam , 21 of 25 and 20 of 25 patients ( p < 0.01 ) reported more than 50 % reduction of pain , whereas after 65 mg propoxyphene 18 of 25 ( p < 0.05 ) and after placebo 11 of 25 reported reduction in pain . Relative efficacy , based on summed pain intensity differences , showed measurable but modest dose‐dependent analgesia with nefopam , suggesting that the effectiveness of 65 mg propoxyphene lay between 45 mg nefopam and placebo . Side effects included mild dizziness and hypothermia after nefopam and mild elevation of diastolic arterial pressure after nefopam and propoxyphene . Our results suggest that 45‐ and 90‐mg doses of nefopam induced more analgesia than 65 mg propoxyphene in the relief of episiotomy pain Meclofenamate sodium , a nonsteroidal anti-inflammatory agent , was compared at two dose levels ( 100 mg and 200 mg ) with codeine ( 60 mg ) and placebo in a double-blind , r and omized study of 218 women after normal vaginal delivery . The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain . Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity . The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain . Adverse experiences with the study medications were minimal ( 6.4 % ) . Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium . Meclofenamate sodium is a safe , effective analgesic for acute episiotomy pain Thirty post-partum patients , aged 19 to 37 years , were treated for episiotomy pain and inflammation with either 1600 mg ibuprofen ( 400 mg every 6 hours ) or placebo daily for 7 days in a completely r and omized , double-blind study . Pain intensity , movement restriction and extent of swelling in the episiotomy were recorded prior to treatment and at intervals of 1 , 3 , 5 and 7 days . The difference scores of pain intensity , movement restriction and extent of swelling were calculated from the differences between pretreatment and post-treatment values . By all methods of evaluation , ibuprofen was significantly more effective than placebo at 1 and 3 days after the initiation of the treatment . Only 2 minor side-effects were recorded , both in the placebo group A double-blind controlled trial was carried out in 267 patients with moderate to severe pain following episiotomy to compare the pain relief provided over a 6-hour period by a single oral dose of 500 mg dipyrone , 500 mg aspirin or placebo . The results showed that dipyrone and aspirin were both significantly superior to placebo . Pain relief with dipyrone was already apparent at 30 minutes after drug intake , and was of significantly longer duration than that of aspirin . No side-effects were reported Our purpose was to compare the analgesic efficacy of single oral doses of ibuprofen , zomepirac , aspirin , and placebo in severe postepisiotomy pain . One hundred twenty subjects participated in a double‐blind , single‐dose , parallel‐group , 4‐hr trial comparing 400 mg ibuprofen , 100 mg zomepirac sodium , 600 mg aspirin , and placebo . For most parameters , including the sum of the pain intensity differences ( SPID ) and the sum of the hourly pain relief values ( TOTAL ) , which are summary variables , each of the drugs was more effective than placebo . Ibuprofen was more effective than aspirin and zomepirac . Zomepirac and aspirin were equally effective for most of the analgesic variables . There were no adverse effects . Ibuprofen , 400 mg , is an effective oral analgesic and is more effective than 100 mg zomepirac and 600 mg aspirin in most parameters of pain Groups of 30 postepisiotomy patients were administered single oral doses of fenoprofen calcium ( 0 , 200 , 400 , or 600 mg acid equivalent ) and /or propoxyphene napsylate ( 0 , 50 , 100 , or 150 mg ) . The complete block design permits analysis of variance with determination of orthogonal medication contrasts . Evaluation of the analgesia scores indicates that both drugs were effective . In comparison with the appropriate placebo control , propoxyphene is associated with an increase in elicited adverse reports and fenoprofen is associated with a decrease in adverse reports . The two drugs are additive when given together Women with gestational diabetes mellitus ( GDM ) have a substantial risk of subsequently developing type 2 diabetes . This risk may be mitigated by engaging in healthy eating , physical activity , and weight loss when indicated . Since postpartum depressive symptoms may impair a woman ’s ability to engage in lifestyle changes , we sought to identify factors associated with depressive symptoms in the early postpartum period among women with recent GDM . The participants are part of the baseline cohort of the TEAM GDM ( Taking Early Action for Mothers with Gestational Diabetes Mellitus ) study , a one-year r and omized trial of a lifestyle intervention program for women with a recent history of GDM , conducted in Boston , Massachusetts between June 2010 and September 2012 . We administered the Edinburgh Postnatal Depression Scale ( EPDS ) at 4–15 weeks postpartum to women whose most recent pregnancy was complicated by GDM ( confirmed by laboratory data or medical record review ) . An EPDS score ≥9 indicated depressive symptoms . We measured height and thyroid stimulating hormone , and administered a question naire to collect demographic data and information about breastfeeding and sleep . We calculated body mass index ( BMI ) using self-reported pre-pregnancy weight and measured height . We review ed medical records to obtain data about medical history , including history of depression , mode of delivery , and insulin use during pregnancy . We conducted bivariable analyses to identify correlates of postpartum depressive symptoms , and then modeled the odds of postpartum depressive symptoms using multivariable logistic regression . Our study included 71 women ( mean age 33 years ± 5 ; 59 % White , 28 % African-American , 13 % Asian , with 21 % identifying as Hispanic ; mean pre-pregnancy BMI 30 kg/m2 ± 6 ) . Thirty-four percent of the women scored ≥9 on the EPDS at the postpartum visit . In the best fit model , factors associated with depressive symptoms at 6 weeks postpartum included cesarean delivery ( aOR 4.32 , 95 % CI 1.46 , 13.99 ) and gestational weight gain ( aOR 1.21 [ 1.02 , 1.46 ] , for each additional 5 lbs gained ) . Use of insulin during pregnancy , breastfeeding , personal history of depression , and lack of a partner were not retained in the model . Identifying factors associated with postpartum depression in women with GDM is important since depression may interfere with lifestyle change efforts in the postpartum period . In this study , cesarean delivery and greater gestational weight gain were correlated with postpartum depressive symptoms among women with recent GDM ( Clinical trials.gov NCT01158131 ) Background . The treatment of pain from episiotomy or from tearing of perineal tissues during childbirth is often unapplied , although discomfort may be severe . We performed a r and omized double‐blind controlled trial to compare the effectiveness and side‐effects of two analgesics in the management of postpartum perineal pain . Patient preference toward the two medications was also analyzed Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25 , 50 and 100 mg , aspirin 600 mg , and placebo in the relief of moderate to severe post-episiotomy pain . One hundred and fifty-two evaluable patients completed a r and omized , double-blind , stratified , parallel groups study . They were observed over a six hour period by one nurse-observer . Based upon each of the summary efficacy measures SPID , TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief , each of the four active treatments were statistically superior to placebo . Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg , but the differences were not statistically significant . Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg . There were no observed or reported adverse effects OBJECTIVE The objective of this single-center , single-dose , double-blind r and omized parallel group study was to evaluate the analgesic efficacy of a new liquid formulation of ketoprofen at two dose levels ( 25 mg or 50 mg ) compared to a commercially available liquid form of dipyrone 500 mg and placebo with all treatments administered as drops to patients with severe postepisiotomy pain . METHODS The study was design ed with a sample size of 69 patients per treatment for a total of 276 patients . However , due to administrative changes at the site , the study was prematurely terminated ; thus only 108 patients ( 26 to 28 patients per treatment ) , 18 years or older , with severe postepisiotomy pain were r and omized to one of the four treatments . Treatments were assessed over a 6-hour period using st and ard scales for pain intensity and pain relief and a number of derived variables based on these data . Since the study medications were not identical in appearance , the preparation and administration of the study medication , and the observation of the patient , were carried out by two different individuals to maintain double-blind conditions . RESULTS All active treatments were significantly superior to placebo for several measures of analgesia including 4-hour and 6-hour SPID and TOTPAR scores . The global rating was assessed as " good " or " excellent " by over 75 % of the patients in the active treatment groups compared to 7.4 % of the patients in the placebo group . Reduction in pain intensity was very similar for the two-dose levels of ketoprofen and the comparator dipyrone 500 mg . CONCLUSION Ketoprofen 25 mg or 50 mg , and dipyrone 500 mg seem to be equally suited for use as pain relief medication after minor surgery , as well as episiotomy . This study did not demonstrate a need for more than 25 mg of ketoprofen in postepisiotomy pain . All treatments were well tolerated . No adverse events were reported Substitutes for aspirin devoid of troublesome effects are needed . A potential c and i date , ibuprofen , heretofore marketed outside the United States as an antiarthritic , was compared in single oral doses of 300 and 900 mg with aspirin , 900 mg , and placebo in a parallel balanced r and omized double‐blind design in 80 patients with pain due to episiotomy . Over the 6 hours of evaluation , there was pain reduction greater than 50 per cent in 17 of 20 patients treated with either dose of ibuprofen ( p < 0.01 ) , in 18 of 20 patients treated with aspirin ( p < 0.001 ) , and in only 6 of 20 patients treated with placebo . With the two doses of ibuprofen , pain relief , as measured by pain intensity differences ( PID ) was similar to that with aspirin with respect to time of onset , degree and duration of analgesia . Reported side effects with ibuprofen were insignificant A r and omised controlled trial was conducted to investigate efficacy of paracetamol and dexketoprofen trometamol for perineal pain relief after perineal repair . Subjects were r and omly assigned to receive two doses of either 50 mg of intravenous dexketoprofen trometamol via slow i.v . infusion ( Group I , n = 49 ) or 1,000 mg of paracetamol via intravenous infusion ( Group II , n = 46 ) . The main outcome measure was a VAS ( visual analogue scale ) for pain recorded at 1 h ( VAS 1 ) . A total of 82 patients were included in the final analysis ( Group I , n = 41 ; Group II , n = 41 ) . There was no difference among groups in terms of pain scores at the beginning ( VAS 0 ) . The pain was decreased in 70 % of the patients in Group I and in 62 % of the patients in Group II ( p = 0.502 ) . Both paracetamol and dexketoprofen are effective in perineal pain relief after episiotomy or perineal tear repair OBJECTIVES This study examined women 's perceptions of early infant feeding experiences and identified early postpartum barriers to successful breastfeeding . SUBJECTS AND METHODS We conducted semistructured exit interviews at 6 months postpartum with a sub sample of participants ( n=67 ) enrolled in two r and omized controlled trials of breastfeeding promotion . Study arms included ( 1 ) routine pre- and postnatal visits with an International Board Certified Lactation Consultant ( IBCLC ) ( LC group ) , ( 2 ) electronically prompted guidance from prenatal care providers ( EP group ) , ( 3 ) EP+LC combined , and ( 4 ) st and ard of care ( control group ) . Interview transcripts were coded using grounded theory and analyzed in MAXqda . Code matrices were used to identify early postpartum breastfeeding barriers and were further examined in relation to treatment group using a mixed methods analysis . RESULTS The majority of the participants reported experiencing at least one barrier to breastfeeding . Barriers to breastfeeding were more commonly reported in the early postpartum than late postpartum period . The most common barrier during the early postpartum period was the perception of inadequate milk supply ( " lactational " ) ( n=18 ) , followed by problems with latch , medical problems that were perceived as precluding breastfeeding , and medical staff and hospital practice s. Participants frequently reported that the IBCLCs assisted them in anticipating , managing , and overcoming these barriers . CONCLUSIONS Our findings underscore the importance of integrating IBCLCs into routine pre- and postpartum care because they provide critical support that effectively addresses early postpartum barriers to breastfeeding The analgesic effectiveness of aqueous and alcoholic formulations of lignocaine ( 5 % ) spray was compared with that of mefenamic acid ( 500 mg ) or placebo in a double-blind study in 103 primiparous patients complaining of moderate or severe perineal pain associated with episiotomy . The results , assessed after a single dose , showed that the aqueous lignocaine formulation provided a level of pain relief superior to that obtained with the alcoholic formulation or placebo , and similar to that obtained with mefenamic acid The analgesic efficacy of fluproquazone at 100 mg and 200 mg doses , was measured in 160 patients with episiotomy pain and was compared to that of aspirin ( 650 mg ) and placebo . The 100-mg dose of fluproquazone was more effective in relieving episiotomy pain than the 200-mg dose of fluproquazone , aspirin or placebo in terms of mean pain intensity scores after 1 h. All active compounds were more effective than placebo by all criteria Meclofenamate sodium was compared , double-blind , with codeine and placebo for the treatment of acute episiotomy pain . One hundred sixty-eight women with moderate or severe episiotomy pain after normal delivery were assigned r and omly to one of four treatment groups : one received meclofenamate sodium 200 mg at dose 1 and 100 mg at doses 2 and 3 ; one received meclofenamate sodium 100 mg at dose 1 and 50 mg at doses 2 and 3 ; one received codeine 60 mg at all three doses ; and one received placebo at all three doses . Efficacy measurements were evaluated periodically for 6 hours after medication . After the first administration , both doses of meclofenamate sodium were significantly superior to placebo and to codeine from 2 - 6 hours in pain intensity difference and pain relief . For second and third doses , data were available for too few patients to allow valid analysis and interpretation . Adverse effects occurred in 4 patients in each meclofenamate sodium group , and in 8 in the codeine group and in 6 in the placebo group . The study indicates that single 100- and 200-mg doses of meclofenamate sodium are as safe as , and significantly more effective than , codeine 60 mg or placebo for episiotomy pain |
10,358 | 28,362,060 | Based on very low- quality evidence from network meta- analysis , we found no evidence of difference between different immunosuppressive regimens .
We found very low- quality evidence from network meta- analysis and low- quality evidence from direct comparison that cyclosporine A causes more retransplantation compared with tacrolimus . | BACKGROUND As part of liver transplantation , immunosuppression ( suppressing the host immunity ) is given to prevent graft rejections result ing from the immune response of the body against transplanted organ or tissues from a different person whose tissue antigens are not compatible with those of the recipient .
The optimal maintenance immunosuppressive regimen after liver transplantation remains uncertain .
OBJECTIVES To assess the comparative benefits and harms of different maintenance immunosuppressive regimens in adults undergoing liver transplantation through a network meta- analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy . | Efficacy and safety of protein kinase C inhibitor sotrastaurin ( STN ) with tacrolimus ( TAC ) was assessed in a 24‐month , multicenter , phase II study in de novo liver transplant recipients . A total of 204 patients were r and omized ( 1:1:1:1 ) to STN 200 mg b.i.d . + st and ard‐exposure TAC ( n = 50 ) or reduced‐exposure TAC ( n = 52 ) , STN 300 mg b.i.d . + reduced‐exposure TAC ( n = 50 ) , or mycophenolate mofetil ( MMF ) 1 g b.i.d . + st and ard‐exposure TAC ( control , n = 52 ) ; all with steroids . Owing to premature study termination , treatment comparisons were only conducted for Month 6 . At Month 6 , composite efficacy failure rates ( treated biopsy‐proven acute rejection episodes of Banff grade ≥1 , graft loss , or death ) were 25.0 % , 16.5 % , 20.9 % and 15.9 % for STN 200 mg + st and ard TAC , STN 200 mg + reduced TAC , STN 300 mg + reduced TAC and control groups , respectively . Median estimated glomerular filtration rates were 84.0 , 83.3 , 81.1 and 75.3 mL/min/1.73 m2 , respectively . Gastrointestinal events ( constipation , diarrhea , and nausea ) , infection , and tachycardia were more frequent in STN groups . More patients in STN groups experienced serious adverse events compared with the control group ( 62.3–70.8 % vs. 51.9 % ) . STN‐based regimens were associated with a higher efficacy failure rate and higher incidence of adverse events with no significant difference in renal function between the groups BACKGROUND Tacrolimus ( Tac ) and mycophenolate mofetil ( MMF ) are newly approved immunosuppressive agents . However , the safety and efficacy of the combination of MMF and Tac in primary liver transplantation has not been determined . METHODS An Institutional Review Board-approved , open-label prospect i ve r and omized protocol was initiated to study the efficacy and toxicity of Tac and steroids ( double-drug therapy ) versus Tac , steroids , and MMF ( triple-drug therapy ) in primary adult liver transplant recipients . Both groups of patients began on the same doses of Tac and steroids . Patients r and omized to triple-drug therapy also received 1 g of MMF twice a day . RESULTS Between August 1995 and January 1997 , 200 patients were enrolled , 99 in double-drug therapy and 101 in triple-drug therapy . All patients were followed until May 1997 , with a mean follow-up of 12.7 months . During the study period , 28 of 99 patients in double-drug therapy received MMF to control ongoing acute rejection , nephrotoxicity , and /or neurotoxicity . On the other h and , 61 patients in triple-drug therapy discontinued MMF for infection , myelosuppression , and /or gastrointestinal disturbances . By an " intention-to-treat analysis , " the actuarial 1-year patient survival rate was 85.1 % in double-drug therapy and 83.1 % in triple-drug therapy ( P=0.77 ) . The actuarial 1-year graft survival rate was 80.2 % for double-drug therapy and 79.2 % for triple-drug therapy ( P=0.77 ) . Forty-one patients ( 41.4 % ) in double-drug therapy and 32 ( 31.7 % ) in triple-drug therapy had at least one episode of rejection , but this was not statistically significant ( P=0.15 ) . The mean maintenance dose of corticosteroids was slightly lower in triple-drug compared with double-drug therapy . CONCLUSION Patient and graft survival rates were similar in both groups . There was a trend to a lower incidence of rejection , reduced nephrotoxicity , and a lesser amount of maintenance corticosteroids in triple-drug therapy compared with double-drug therapy Although steroid withdrawal has been successfully performed in heart and kidney transplant recipients , no controlled studies of SW have been carried out in liver transplant patients . To evaluate this possibility a prospect i ve controlled study was carried out in 46 liver transplant recipients operated on after may 1991 . They all received a sequential quadruple immunosuppression consisting of 3 mg/kg antithymocyte globulins ( RATG ) for the first 5 postoperative days , cyclosporin A ( starting from day 3 - 5 and maintaining parenteral whole-blood trough levels at 200 - 300 ng/ml during the first month and at 150 - 250 thereafter ) , azathioprine ( 1 mg/kg per day for the first month ) and steroids . Prednisone was started at a dose of 200 mg per day 1 and then tapered to 20 mg/day over the first posteroperative week ; this dose was maintained until day 90 when the patients were r and omly allocated either to long-term steroid therapy ( 0.1 mg/kg per day ) or to steroid withdrawal . Minimum follow-up after r and omization was 6 months ( 6 - 27 months ) . Liver biochemistry was checked at regular intervals throughout the follow-up period . Liver biopsies were performed whenever clinical ly indicated and also in the first 19 patients during readmission for annual review . The incidence ot acute and chronic rejection 90 days from liver transplantation was 2.5 % in patients maintained on long-term therapy . No patient in the steroid-withdrawal group had experienced either an acute or a chronic rejection episode so far . Steroid-related complications did not differ significantly between the two groups . The most recent interim analysis showed that steroid withdrawal is a safe undertaking in liver transplant recipients and may be successfully accomplished in almost all patients We studied the outcome of 345 liver transplant patients who received tacrolimus‐based immunosuppressive therapy either as a dual regimen ( with corticosteroids , n=172 ) or as a triple regimen ( with corticosteroids and azathioprine , n=173 ) for 3 months after transplantation ( 3‐month cohort ) . A further analysis was conducted for the first 195 patients r and omised ( dual n=100 , triple n=95 ) who were followed up for 12 months after transplantation ( 12‐month cohort ) . For the 3‐month cohort , patient survival was 90.7 % ( dual ) and 91.9 % ( triple ) , graft survival after 3 months was 88.4 % ( dual therapy ) and 89.6 % ( triple therapy ) . Acute rejections were experienced by 67/172 , 39.0 % of patients on dual therapy and by 60/173 , 34.7 % of patients on triple therapy ; corticosteroid‐resistant rejections were reported in 9 patients ( 5.2 % ) in either treatment group . The overall safety profile was similar for the two treatment groups . Significant differences , however , were found for thrombocytopenia ( dual 13/172 , 7.6 % , triple 37/173 , 21.4 % , p<0.001 ) and leukopenia ( dual 4/172 , 2.3 % , triple 24/173 , 13.9 % , p<0.001 ) . For the 12‐month cohort , patient survival was 85.6 % ( dual ) and 88.4 % ( triple ) after 1 year . Graft survival was 81.7 % ( dual ) and 85.2 % ( triple ) 12 months after transplantation . Acute rejections were reported for 38/100 , 38.0 % of patients on dual therapy and 36/95 , 37.9 % of patients on triple therapy , corticosteroid‐resistant rejections were 7/100 , 7.0 % ( dual ) and 7/95 , 7.4 % ( triple ) of patients . In the 12‐month cohort , no significant differences in the safety profiles of the treatment groups were found . We conclude that both tacrolimus‐based dual and triple drug regimens provide effective and safe immunosuppression following orthotopic liver transplantation This r and omized , prospect i ve , multicenter trial compared the safety and efficacy of steroid-free immunosuppression ( IS ) to the safety and efficacy of 2 st and ard IS regimens in patients undergoing transplantation for hepatitis C virus ( HCV ) infection . The outcome measures were acute cellular rejection ( ACR ) , severe HCV recurrence , and survival . The patients were r and omized ( 1:1:2 ) to tacrolimus ( TAC ) and corticosteroids ( arm 1 ; n = 77 ) , mycophenolate mofetil ( MMF ) , TAC , and corticosteroids ( arm 2 ; n = 72 ) , or MMF , TAC , and daclizumab induction with no corticosteroids ( arm 3 ; n = 146 ) . In all , 295 HCV RNA-positive subjects were enrolled . At 2 years , there were no differences in ACR , HCV recurrence ( biochemical evidence ) , patient survival , or graft survival rates . The side effects of IS did not differ , although there was a trend toward less diabetes in the steroid-free group . Liver biopsy sample s revealed no significant differences in the proportions of patients in arms 1 , 2 , and 3 with advanced HCV recurrence ( ie , an inflammation grade ≥ 3 and /or a fibrosis stage ≥ 2 ) in years 1 ( 48.2 % , 50.4 % , and 43.0 % , respectively ) and 2 ( 69.5 % , 75.9 % , and 68.1 % , respectively ) . Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV , steroid sparing has no clear advantage in comparison with traditional IS Background . Calcineurin inhibitors ( CNIs ) play the key role in immunosuppressive protocol s yet are often associated with numerous side effects . Renal insufficiency , hypertension , hyperglycemia , and increased risk of secondary malignancy are major problems in short- and long-term follow-up of liver transplant patients . Mycophenolate mofetil ( MMF ) has proved to be a potent immunosuppressive agent free of the CNI-associated side effects . Patients and Methods . One hundred fifty patients who received liver transplantation at our institution ( 1998–2003 ) were prospect ively r and omized : 75 patients continued CNI st and ard therapy , 75 patients were switched to MMF monotherapy , and follow-up was 5 years . Incidence of rejection , renal complication , cardiovascular , neurological and gastrointestinal adverse effects , and diabetes and malignancy development was recorded . Graft biopsies were performed every 2 to 3 years . Results . No significant difference regarding the incidence of acute rejection was detected . A trend to higher rejection frequency was apparent in the MMF monotherapy group . Chronic rejection was absent ; organ and patient survival were identical in the two groups . No significant difference occurred concerning the incidence of cardiovascular , gastrointestinal or neurological adverse effects , or the development of malignancies . Renal function improved significantly in patients with renal insufficiency when patients treated with CNI were switched to MMF monotherapy . Conclusion . MMF monotherapy may serve as safe long-term immunosuppression after liver transplantation for a subgroup of patients . Especially for patients with renal insufficiency MMF offers immunosuppression without the risk of nephrotoxicity 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 To provide a more definitive assessment of the efficacy and safety of tacrolimus therapy in comparison with cyclosporin , the extended follow-up of the European multicentre study is reported . Two-year Kaplan-Meier estimates indicated significant reductions in acute ( tacrolimus 45.4 % , cyclosporin 55.8 % ; P = 0.006 ) , refractory ( 1.2 % versus 6.4 % ; P = 0.003 ) and chronic rejection ( 2.0 % versus 6.9 % ; P = 0.015 ) despite significantly lower steroid usage in patients receiving tacrolimus therapy . Patient and graft survival rates ( 80.6 % versus 74.8 % and 74.5 % versus 70.0 % , respectively ) were also superior , although these failed to reach statistical significance . Safety profiles were comparable for most major categories ( including renal , neurological and glucose metabolic disorders ) and in certain aspects were more favourable for tacrolimus . Hypertension ( 28.0 % versus 39.6 % , P < 0.01 ) and cytomegalovirus infection ( 14.8 % versus 22.3 % , P < 0.01 ) , two events with important long-term clinical consequences , were reported significantly less frequently . Hirsutism ( 0.0 % versus 8.7 % , P < 0.01 ) and gum hyperplasia ( 0.0 % versus 2.3 % , P < 0.05 ) were absent in patients receiving tacrolimus . Tacrolimus appears to provide effective and safe long-term immunosuppression We conducted a multicenter r and omized study in liver transplantation to compare st and ard‐dose tacrolimus to reduced‐dose tacrolimus with mycophenolate mofetil to reduce the occurrence of tacrolimus side effects . Two primary outcomes ( censored criteria ) were monitored during 48 weeks post‐transplantation : occurrence of renal dysfunction or arterial hypertension or diabetes ( evaluating benefit ) and occurrence of acute graft rejection ( evaluating risk ) . Interim analyses were performed every 40 patients to stop the study in the case of increased risk of graft rejection . One hundred and ninety‐five patients ( control : 100 ; experimental : 95 ) had been included when the study was stopped . Acute graft rejection occurred in 46 ( 46 % ) and 28 ( 30 % ) patients in control and experimental groups , respectively ( HR = 0.59 ; 95 % CI : [ 0.37–0.94 ] ; p = 0.024 ) . Renal dysfunction or arterial hypertension or diabetes occurred in 80 ( 80 % ) and 61 ( 64 % ) patients in control and experimental groups , respectively ( HR = 0.68 ; 95 % CI : [ 0.49–0.95 ] ; p = 0.021 ) . Renal dysfunction occurred in 42 ( 42 % ) and 23 ( 24 % ) patients in control and experimental groups , respectively ( HR = 0.49 ; 95 % CI : [ 0.29–0.81 ] ; p = 0.004 ) . Leucopoenia ( p = 0.001 ) , thrombocytopenia ( p = 0.017 ) and diarrhea ( p = 0.002 ) occurred more frequently in the experimental group . Reduced‐dose tacrolimus with mycophenolate mofetil reduces the occurrence of renal dysfunction and the risk of graft rejection . This immunosuppressive regimen could replace full‐dose tacrolimus in adult liver transplantation As liver transplantation ( LT ) is now being performed with excellent 1-year graft survival rates of 85 % to 90 % , attention has been shifted to reducing long-term complications of calcineurin inhibitors ( CNI ) . We r and omized LT patients ( 2:1 ) who displayed renal dysfunction under CNI treatment to either mycophenolate mofetil ( MMF ) ( 1000 mg twice a day ) followed by stepwise reduction of CNI ( n = 21 ; Tac trough levels < 4 ng/mL , CsA trough levels < 50 ng/mL ) ; or continue their current CNI dose ( n = 11 ; control group ) . Three months after study entry , we observed significantly decreased mean values in the CNI reduction group of serum creatinine ( 1.88 + /- 0.36 versus 1.58 + /- 0.33 mg/dL , P < .001 ) and BUN ( 39.2 + /- 11.8 versus 29.9 + /- 9.59 mg/dL , P < .001 ) with a significantly increased GFR ( 51.4 + /- 10.8 versus 61.6 + /- 14.1 mL/min , P < .001 ) . Improved renal function in these long-term LT recipients ( 5.6 + /- 3.6 years posttransplant ; range , 2 to 13 years ) suggests at least a partial reversibility of CNI-induced renal damage . Furthermore , we found an improved lipid profile as well as a significantly decreased mean systolic ( 140 + /- 19 versus 130 + /- 14 mm Hg , P < .01 ) and diastolic ( 82 + /- 9 to 74 + /- 8 mm Hg , P < .001 ) blood pressure 3 months after introduction of MMF therapy . Additionally , transaminases significantly improved in the CNI reduction group within this time period ( ALT 37.9 + /- 25.9 versus 25.2 + /- 13.2 , P < .05 ) . MMF and CNI-reduced immunosuppressive regimens may improve long-term patient survival , suggesting a broad application within the liver transplant setting OBJECTIVE We conducted a treatment trial to determine the relative toxicity of FK-506 and cyclosporine A ( CSA ) in liver transplant recipients . DESIGN Between October 1990 and October 1991 , 37 patients were enrolled in an open-labeled , r and omized study of two immunosuppressive regimens after liver transplantation . MATERIAL AND METHODS Of the 23 men and 14 women , 20 received FK-506 plus prednisone , and 17 received CSA plus prednisone and azathioprine . Renal function was assessed before and after transplantation ( day 1 , month 1 , month 4 , and month 12 ) by measurements of serum creatinine ( SCr ) and glomerular filtration rate ( GFR ) as determined by urinary iothalamate or creatinine clearance ( or both ) . FK-506 trough plasma levels ( enzyme immunoassay ) were to be maintained between 0.2 and 5.0 ng/mL , and CSA trough blood levels ( whole blood high-performance liquid chromatography ) were to be maintained between 250 and 400 ng/mL. Severe nephrotoxicity was defined as sudden decreases in urine output to less than 10 mL/h or rapid increases in SCr ( more than 0.5 mg/dL daily ) that necessitated withdrawal of study medication for more than 48 hours . Mean patient age and values for SCr and GFR were comparable between the two groups at entry . RESULTS Both study groups demonstrated a similar deterioration in renal function during a 12-month follow-up , although patients who received FK-506 had a significantly ( P < 0.05 ) lower GFR when measured at 12 months than did patients treated with CSA ( 45 + /- 4 versus 64 + /- 6 mL/min per body surface area ) . Mild nephrotoxicity that responded to decreased drug doses was noted in 9 CSA-treated patients ( 53 % ) and 10 FK-506-treated patients ( 50 % ) . Severe nephrotoxicity that necessitated drug withdrawal occurred in only four patients , all of whom were in the FK-506 group . These severe nephrotoxic reactions to FK-506 occurred early after transplantation , often during intravenous administration of the drug , and were not associated with poor liver allograft function or drug levels outside the therapeutic range . CONCLUSION Both FK-506 and CSA are significantly nephrotoxic in liver transplant recipients . In this trial , however , we observed an early development of severe nephrotoxic reactions only in some patients who received FK-506 The immunosuppressive effect of a monoclonal antibody ( moAb ) , BT563 , directed to the alpha-chain of the IL-2R ( CD25 ) , was analyzed in a prospect i ve nonr and omized trial and a prospect i ve r and omized trial . Primary objectives were evaluation of the incidence of acute rejections and infections ; secondary objectives were safety and tolerability of the moAb . A total of 28 patients were enrolled ( phase II ) to receive 10 mg/day of BT563 ( 12 days ) as immunoprophylaxis in combination with cyclosporine , azathioprine , and low-dose steroids . Subsequently 32 patients were r and omly assigned ( phase III ) to receive BT563 ( 10 mg/day ) for 12 days or ATG ( 5 mg/kg/day ) for 7 days in addition to cyclosporine and low-dose steroids . No side effects of the BT563 treatment were noted . The actuarial survival was 82 % at 12 months in the phase II trial and 92 % at 12 months in both arms of the phase III trial . There was one acute rejection in the phase II trial . No acute rejections were noted in the BT arm of the phase III trial and 5 acute rejections were treated in the ATG arm . In the phase II trial 7 infectious episodes were observed , while one infection was seen in the BT arm and 7 in the ATG arm of the triple immunosuppression phase III trial . In all patients circulation of coated CD25 + lymphocytes was observed during BT563 treatment ; there was no evidence of depletion or modulation of CD25 + cells . Mean serum levels of BT563 ranged from 1.6 to 7.6 microgram/ml throughout the therapy . An antimurine response was seen in 82 % ( phase II ) and 100 % ( phase III ) of the patients . Antirabbit antibodies were found in 56 % of the patients treated with ATG . Analysis of the antimurine response specificity revealed in 56 % blocking anti-isotypic antibodies and only in 3 % of the patients an anti-idiotypic response . The data of the study presented suggest that therapy with an anti IL-2R moAb is at least equal to ATG application according to the incidence of acute rejections and infections Basiliximab , a high-affinity chimeric monoclonal antibody , is effective in reducing acute rejection episodes in renal allograft recipients . We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients . Adult recipients of a primary cadaveric liver transplant were r and omized to treatment , stratified by hepatitis C virus ( HCV ) seropositivity . Patients were administered 40 mg of basiliximab ( n = 188 ) or placebo ( n = 193 ) as two 20-mg bolus injections days 0 and 4 , plus cyclosporine and steroids . Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point , including death or graft loss , and were assessed at 6 and 12 months and by HCV cohort . Because of differential efficacy responses between HCV-positive and HCV-negative cohorts , an additional analysis incorporating HCV recurrence as a component of treatment failure , termed problem-free transplant , was introduced . Safety and tolerability were monitored over the 12 months of the study . All 381 patients were assessable , and no meaningful differences in background characteristics were apparent between treatment groups . Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1 % in the basiliximab group versus 43.5 % in the placebo group . For death , graft loss , or first biopsy-confirmed acute rejection , rates were 44.1 % versus 52.8 % , respectively . The reduction in rejection episodes was concentrated in the HCV-negative cohort ( 14.5 % relative to placebo ; P = .034 ) , with a much smaller difference ( 2.9 % ) in the HCV-positive cohort . For HCV-positive patients , problem-free transplant was shown at 12 months in 26.6 % of the basiliximab group versus 11.6 % in the placebo group ( P = .020 ) and for all patients at 12 months in 39.7 % of the basiliximab group versus 30.1 % in the placebo group ( P = .035 ) . The incidence of infection and other adverse events was similar across the two treatment groups . There were 56 deaths ( 25 deaths , basiliximab group ; 31 deaths , placebo group ) over the 12-month study . The intravenous bolus injection was well tolerated . Immunoprophylaxis with 40 mg of basiliximab , in combination with cyclosporine and steroids , reduces the incidence of acute rejection episodes with no clinical ly relevant safety or tolerability concerns . The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant , incorporating recurrence as a component of treatment failure BACKGROUND Prophylactic treatment with ursodeoxycholic acid ( UDCA ) has been reported to reduce the incidence of acute rejection after liver transplantation compared with historical controls . We investigated this in a prospect i ve , r and omized , placebo-controlled multicenter study . METHODS Fifty-four liver transplant patients were allocated to the UDCA treatment group ( 15 mg/kg/day ) , and 48 patients were allocated to the placebo group . Trial medicine was started on the first postoperative day and was given for 3 months . Follow-up was for 12 months . Treatment was stratified for adults with chronic liver disease ( n=77 ) , adults with acute liver failure ( n=10 ) , and children ( n=15 ) . RESULTS The frequency of patients with acute rejection was 65 % in the UDCA treatment group and 68 % in the placebo group . The frequency of steroid-resistant rejection was similar in both groups . The probability of acute rejection , analyzed according to the intention-to-treat policy with Kaplan-Meier analysis , was similar in both treatment groups . No significant differences were found in patient survival and graft survival probabilities . For the biochemical markers of cholestasis , only gamma-glutamyltransferase was significantly improved after 2 months of UDCA treatment . CONCLUSIONS The initial optimistic report of a beneficial effect of prophylactic treatment with UDCA on acute rejection after liver transplantation was not confirmed in this controlled study In a 24‐month prospect i ve , r and omized , multicenter , open‐label study , de novo liver transplant patients were r and omized at 30 days to everolimus ( EVR ) + Reduced tacrolimus ( TAC ; n = 245 ) , TAC Control ( n = 243 ) or TAC Elimination ( n = 231 ) . R and omization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy‐proven acute rejection ( tBPAR ) . The incidence of the primary efficacy endpoint , composite efficacy failure rate of tBPAR , graft loss or death postr and omization was similar with EVR + Reduced TAC ( 10.3 % ) or TAC Control ( 12.5 % ) at month 24 ( difference −2.2 % , 97.5 % confidence interval [ CI ] −8.8 % , 4.4 % ) . BPAR was less frequent in the EVR + Reduced TAC group ( 6.1 % vs. 13.3 % in TAC Control , p = 0.010 ) . Adjusted change in estimated glomerular filtration rate ( eGFR ) from r and omization to month 24 was superior with EVR + Reduced TAC versus TAC Control : difference 6.7 mL/min/1.73 m2 ( 97.5 % CI 1.9 , 11.4 mL/min/1.73 m2 , p = 0.002 ) . Among patients who remained on treatment , mean ( SD ) eGFR at month 24 was 77.6 ( 26.5 ) mL/min/1.73 m2 in the EVR + Reduced TAC group and 66.1 ( 19.3 ) mL/min/1.73 m2 in the TAC Control group ( p < 0.001 ) . Study medication was discontinued due to adverse events in 28.6 % of EVR + Reduced TAC and 18.2 % of TAC Control patients . Early introduction of everolimus with reduced‐exposure tacrolimus at 1 month after liver transplantation provided a significant and clinical ly relevant benefit for renal function at 2 years posttransplant BACKGROUND The long-term complications of immunosuppressive therapy such as diabetes , hypercholesterolemia , and hypertension are a major source of morbidity in liver transplant recipients . In this prospect i ve , r and omized , open-label study we completely withdrew prednisone ( PRED ) 14 days after liver transplantation in an effort to decrease these metabolic complications . Patients were maintained on mycophenolate mofetil ( MMF ) in combination with either cyclosporine ( CsA ; Neoral formulation ) or tacrolimus ( TAC ) . Thus , we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy , toxicity , and effect on posttransplant metabolic complications . METHODS A total of 71 patients were r and omized to receive either TAC-MMF ( n=35 ) or CsA-MMF ( n=36 ) after liver transplantation and were analyzed for patient and graft survival . Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes , hypertension , and hypercholesterolemia . RESULTS The 6-month patient survival rates were 94.4 % for CsA-MMF and 88.6 % for TAC-MMF . Corresponding 6-month graft survival rates were 88.7 % and 85.71 % with no immunologic graft losses in either group . The incidence of biopsy-proven acute rejection was 46 % for CsA-MMF and 42.3 % for TAC-MMF . Six patients were converted from CsA to TAC ( four for recurrent rejection ) and seven patients were converted from TAC to CsA ( four for neurotoxicity ) . Only one patient ( in the TAC-MMF group ) developed new-onset posttransplant diabetes . In contrast , four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant . The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group ( 145.2+/-41.8 mg/dl and 190.3+/-62.2 , respectively ; P<0.001 ) and the incidence of hypertension was lower in the TAC-MMF group ( 12 % vs. 30.3 % in the CsA-MMF group , P<0.01 ) . Both groups had a lower incidence of metabolic complications compared with a historical group ( n=100 ) maintained on CsA and PRED ( 10 mg/day at 6 months ) . CONCLUSIONS MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses . Early PRED withdrawal decreases posttransplant diabetes , hypercholesterolemia , and hypertension , but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients A multiinstitutional r and omized trial was undertaken comparing OKT3 with steroids for treatment of hepatic allograft rejection . All patients received baseline immunosuppression with Cyclosporine ( CsA ) and steroids . At the time of biopsy-confirmed rejection , up to 2 intravenous boluses ( 250–1000 mg ) of methylprednisolone were initially administered . Twenty-eight patients who failed to respond were then r and omly assigned to OKT3 or continued steroid therapy . Rescue therapy with the opposite treatment arm was added after 6 days if the primarily allocated protocol failed . Three of 13 patients assigned to the steroid group responded promptly , and continue with good function 7–12 months later . OKT3 rescue was required in 10 patients who failed to improve despite receiving up to 6 g of methylprednisolone ( mean : 3.3 g/patient ) . One patient died of sepsis and hepatic failure . Rejection was reversed in 9 OKT3-rescue patients , 7 of whom are well 1–17 months later . In the OKT3 group , improved allograft function was observed within 72 hr in 11 of 15 patients . Two patients with inadequate response were successfully rescued with steroids ; 1 patient underwent retransplantation ; and 1 patient developed a biliary fistula that eventually result ed in sepsis and death . In summary , 23 of 28 hepatic recipients ( 82 % ) are alive with the original allograft 1–17 ( mean 7.8 ) months after treatment for acute rejection . Another patient is alive 14 months following retransplantation . Eighteen ( 78 % ) of the survivors required OKT3 as initial ( 11 ) or rescue ( 7 ) therapy , whereas only 5 were successfully managed with steroids . OKT3 is superior to steroids for reversing liver allograft rejection and has greatly reduced the need for retransplantation even in recipients selected on the basis of having failed initial steroid therapy Background . Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation . Interleukin-2 receptor antagonist induction followed by delayed tacrolimus ( Tac ) administration may minimize the renal insult without compromising immunoprotection . Methods . This open , r and omized , multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months ; an observational study was continued for 18 months . Liver transplant patients with a 12-hr serum creatinine ( SrC ) level less than 180 & mgr;mol/L received either delayed Tac with daclizumab induction ( n=98 ) or st and ard Tac ( n=101 ) both combined with mycophenolate mofetil and steroids . The primary endpoint was the incidence of SrC level more than 130 & mgr;mmol/L at 6 months . Results . The incidence was 22.4 % with delayed Tac and 29.7 % with st and ard Tac ( P = ns ) , which remained unchanged at 12 months ( 21.6 % and 23.9 % ) but increasing slightly at 24 months ( 29.0 % and 32.9 % ) , respectively . A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr ( ≤100&mgr;mol/L or > 100 & mgr;mol/L ) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 & mgr;mol/L in the delayed Tac group . Biopsy-proven acute rejection was similar at 6 months ( 17.5 % and 18.75 % ) , 12 months ( 23.5 % and 23.8 % ) , and 24 months ( 24.5 % and 25.7 % ) , respectively . Patient and graft survival in both groups were comparable and good . Similar types and incidences of adverse events were reported in both groups at all time . Conclusions . Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline ACROLIMUS ( Tac ) was approved by the FDA for clinical use in liver transplantation in 1993 and myco-phenolate mofetil ( MMF ) was approved in 1995 for use inkidney transplantation with cyclosporine . The aim of thepresent study was to compare the combination of Tac and steroids ( double therapy , group D ) versus tacrolimus , ste-roids , and MMF ( triple therapy , group T ) in primary adult(age . 18 years ) liver transplantation ( LTx ) . An interimreport was published on the first 200 patients with a meanfollow-up of 12.7 6 0.4 months Background The potential anti-cancer effects of mammalian target of rapamycin ( mTOR ) inhibitors are being intensively studied . To date , however , few r and omised clinical trials ( RCT ) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting , and at present , no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients . Interestingly , since mTOR inhibitors have both immunosuppressive and anti-cancer effects , they have the potential to simultaneously protect against immunologic graft loss and tumour development . Therefore , we design ed a prospect i ve RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant ( LT ) recipients with a pre-transplant diagnosis of HCC . Methods / Design The study is an open-labelled , r and omised , RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC . Patients with a histologically confirmed HCC diagnosis are r and omised into 2 groups within 4 - 6 weeks after LT ; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4 - 6 weeks , at which time sirolimus is initiated . A 21/2 -year recruitment phase is planned with a 5-year follow-up , testing HCC-free survival as the primary endpoint . Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival . The study is a non-commercial investigator-initiated trial ( IIT ) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association ; 13 countries within Europe , Canada and Australia are participating . Discussion If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection , patients should experience less post-transplant problems with HCC recurrence , and therefore could expect a longer and better quality of life . A positive outcome will likely change the st and ard of posttransplant immunosuppressive care for LT patients with HCC.Trial RegisterTrial registered at http://www . clinical trials.gov : NCT00355862(EudraCT Number : 2005 - 005362 - 36 BACKGROUND The long-term ( 5 year ) efficacy and safety of tacrolimus ( FK506 ) and cyclosporine were compared in primary liver transplant recipients who participated in a 1-year r and omized , multicenter trial and a 4-year follow-up extension study . METHODS A total of 529 patients ( 263 tacrolimus group , 266 cyclosporine group ) were r and omized to study drug . Patients were evaluated at 3-month intervals . Patient and graft survival rates , incidence of adverse events , and changes in laboratory and clinical profiles were determined . RESULTS Cumulative 5-year patient and graft survival rates were comparable for the tacrolimus ( 79.0 % , 71.8 % ) and cyclosporine ( 73.1 % , 66.4 % ) groups . However , patient half-life survival was longer for tacrolimus-treated patients ( 25.1+/-5.1 years versus 15.2+/-2.5 years ; P=0.049 ) . Improved patient survival with tacrolimus was also observed for hepatitis C-positive patients ( 78.9 % tacrolimus group versus 60.5 % cyclosporine group ; P=0.041 ) . Both treatments were associated with a low incidence of late acute rejection , late steroid-resistant rejection , and death or graft loss related to rejection . Both treatments demonstrated an acceptable safety profile with maintenance of adequate renal and liver function and a low incidence of malignancy/lymphoproliferative disease and serious infections . CONCLUSIONS Tacrolimus is a safe and effective long-term maintenance immunosuppressive agent in primary liver transplantation Neurological complications were examined in a multicentre , r and omized , parallel-group study of 545 patients undergoing primary liver transplantation to compare the efficacy and safety of FK 506- and cyclosporin A-based immunosuppressive regimens ( CBIR ) . In an additional analysis , patients were divided into early and late r and omized cohorts to detect the influence of protocol amendements that allowed for FK 506 dose reductions . Initial follow-up was for 6 months . Tremor , headache and insomnia were the most frequently reported adverse events involving the neurological system . Whereas these neurological symptoms were observed significantly more often in FK 506-treated patients ( P < 0.05 vs. CsA for the overall population ) , this was no longer the case for the late FK 506 and CBIR cohorts . The risk of FK 506-treated patients developing tremor was related to the initial i.v . dose , the rate of administration of the i.v . dose and the daily dose ( P < 0.01 ) . Headache was significantly correlated with the FK 506 dose ( P < 0.05 ) , and insomnia was not related to any dosing variable . Major neurological symptoms , including psychosis , convulsion , coma , aphasia and intracranial haemorrhage , were reported with a low frequency ( 0.4 - 5.2 % ) , and differences between both treatment groups were neither significant for the overall population nor for the early and late cohorts of FK 506 and CBIR . Data from the late cohorts showed no differences in the overall incidence of neurological adverse events between FK 506- and CBIR-treated patients 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 UNLABELLED The purpose of the study was to introduce mycophenolate mofetil ( MMF ) in liver transplant recipients with renal dysfunction to decrease calcineurin inhibitor ( CNI ) dosages without increasing rejection risk . In this prospect i ve , multicenter , r and omized study , chronic CNI-related renal dysfunction was defined by an increase in serum creatinine with values > 140 micromol/L and < 300 micromol/L. Patients were r and omized in 2 groups . STUDY GROUP combination of MMF ( 2 to 3 g/day ) and reduced dose of CNI > or=50 % of initial dose ; control group : no MMF , but with the ability to reduce CNI doses , but not below 75 % of initial dose . Fifty-six patients were included , 27 in the study group and 29 in the control group . In the study group , there was a significant decrease in serum creatinine values , from 171.7 + /- 24.2 micromol/L at day 0 to 143.4 + /- 19 micromol/L at month 12 and a significant increase in creatinine clearance , from 42.6 + /- 10.9 mL/min to 51.7 + /- 13.8 mL/min . No rejection episode was observed in the study group . In the control group , there was no improvement of renal function , assessed by the changes in serum creatinine values , from 175.4 + /- 23.4 micromol/L at day 0 to 181.6 + /- 63 micromol/L at month 12 , and in creatinine clearance , from 42.8 + /- 12.8 mL/min to 44.8 + /- 19.7 mL/min . The differences between the 2 groups were significant : P = 0.001 for serum creatinine , and P = 0.04 for creatinine clearance . In conclusion , the introduction of MMF combined with the reduction of at least 50 % of CNI dose allowed the renal function of liver transplant recipients to significantly improve at 1 year , without any rejection episode and without significant secondary effects We report the results of a prospect i ve r and omized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin ( ATG‐Fresenius ) plus tacrolimus monotherapy at gradually decreasing doses . Patients were r and omized to either : ( a ) st and ard‐dose tacrolimus plus steroids;or ( b ) peritransplant ATG‐Fresenius plus reduced‐dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation . The primary end‐point was the achievement of very low‐dose tacrolimus ( every‐other‐day or once daily dose with < 5 ng/mL trough levels ) at 12 months after transplantation . Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group ( 52.4 % vs. 25 % ) . Moreover , late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end‐point . This motivated the premature termination of the trial . Tacrolimus trough levels were lower in the ATG‐Fresenius group but no benefits in terms of improved renal function , lower metabolic complications or increased prevalence of tolerance‐related biomarkers were observed . In conclusion , the use of ATG‐Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection , did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits . Clinical Trials.gov identifier : NCT00436722 Abstract Dyslipidemia is common after liver transplantation , but the underlying mechanisms are largely unknown . We studied the lipid profile of 27 liver transplant recipients r and omized to receive either cyclosporin ( CyA , n = 14 ) or tacrolimus ( n = 13 ) and compared them with 20 healthy , matched controls . Before transplantation , patients presented low total and low-density lipoprotein ( LDL ) cholesterol ( as compared to controls ) that increased shortly , i. e. , 3 months , after transplantation . Eighteen months post-transplantation , total and LDL cholesterol levels decreased to pretransplant values but tended to remain higher in CyA-treated patients . However , at that time , prednisone treatment was more prevalent among CyA-treated than tacrolimus-treated patients and fully accounted for the difference in cholesterol levels . Indeed , regardless of therapy , patients not receiving prednisone exhibited lower cholesterol levels than prednisone-treated patients and controls . We conclude that prednisone therapy , rather than CyA or tacrolimus immunosuppression , seems to be the major determinant of increased cholesterol levels 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 As part of a European multicenter study to investigate the potency of FK506 in primary immunosuppression after liver transplantation , this comparison with our conventional cyclosporine-based quadruple regimen was carried out as a controlled , prospect i ve , r and omized trial . The 121 patients entering the study were r and omly assigned to receive immunosuppressive regimens consisting either of FK506 and prednisolone ( FK/n = 61 ) or of cyclosporine , prednisolone , azathioprine , and a 7-day course of rabbit antithymocyte globulin ( CsA/n = 60 ) . Rejection was suspected in the case of scant production of light bile or biochemical graft dysfunction , without evidence of vascular , biliary , or infectious complications . A liver biopsy for confirmation of the diagnosis was obtained each time . Initial therapy entailed a 3-d course of high-dose methyl-prednisolone . Steroid resistant rejections were treated with OKT3 monoclonal antibody or , in the group of primary CsA administration , conversion to FK506 as another treatment option . One-year patient ( FK : 90.2 % ; CsA : 96.7 % ) and graft survival ( FK : 88.5 % ; CsA : 91.7 % ) did not differ significantly . Overall , 41 patients ( 33.9 % ) experienced 50 acute , cellular rejection episodes ( RE ) [ FK : 25 RE in 21 patients ( 34.4 % ) ; CsA : 25 RE in 20 patients ( 33.3 % ) ] . The histological grading ranged from mild ( FK : 14/25 ; CsA : 8/25 ) to moderate ( FK : 9/25 ; CsA : 16/25 ) and severe ( FK : 2/25 ; CsA : 1/25 ) : not significantly different between the two groups . In the CsA-based group , three additional rejection episodes were classified as early chronic ( n = 1 ) and chronic rejection ( n = 2 ) . ( ABSTRACT TRUNCATED AT 250 WORDS This r and omized , comparative study assessed the long-term efficacy and tolerability of thymoglobulin ( TMG ) induction in 93 liver transplant patients with an initial regimen of tacrolimus ( Tac ) , mycophenolate mofetil ( MMF ) , and steroids . Forty-four patients were r and omly allocated to the TMG+ group , and 49 patients were r and omly allocated to the TMG- group . In both groups , Tac was given orally at the initial daily dose of 0.075 mg/kg twice daily , and MMF was given at the initial daily dose of 2 g/day . Steroid withdrawal was planned at 3 months after liver transplantation . The results were evaluated with respect to acute rejection incidence , patient and graft survival , graft function , and medical complications until 5 years or death for all patients . No significant differences were found between groups for the incidence of acute rejection at 5 years ( 11.4 % versus 14.3 % ) , 5-year patient survival ( 77.3 % versus 87.8 % ) , graft function , or postoperative renal function . One patient in the TMG- group underwent retransplantation . There was no difference between groups with respect to the incidence of medical complications , excepted for a higher rate of leukopenia in the TMG+ group , during the 5-year follow-up . In conclusion , the results of this prospect i ve r and omized study suggest that the addition of TMG to a triple immunosuppressive regimen ( Tac , MMF , and steroids ) did not modify the incidence of acute rejection episodes or long-term survival and was responsible for increased leukopenia rates Background Induction immunosuppression with anti-thymocyte globulin ( ATG ) provides potential benefits after liver transplantation ( LT ) . However , its use in patients with LT and hepatitis C ( HCV ) is controversial . Aim To evaluate the 1- and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression ( IPI ) after LT . Methods A total of 49 patients undergoing their first LT for HCV were r and omized to receive ATG during IPI . Patient survival and HCV recurrence were determined at 1 and 2 years . The frequency of acute cellular rejection ( ACR ) , infections , and neoplasms was also evaluated . Results Twenty-six patients were r and omized to receive ATG ( Arm-1 ) and 23 to st and ard induction therapy ( Arm-2 ) . Those given ATG had lower HCV recurrence ( 26.9 vs 73.9 % , p = 0.001 ) . The 1- and 2-year patient survival rates were similar for both arms ( p = 0.33 ) . Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 ( p = 0.562 ) . There was a greater proportion of fungal infections in Arm-1 ( 19.2 vs 0 % , p = 0.032 ) . Conclusions ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT . This , however , did not affect the 1- and 2-year survival and the frequency of ACR , infections , or neoplasms In a r and omized prospect i ve study of liver transplant recipients , we compared prophylaxis with OKT3 , steroids , and azathioprine to cyclosporine , steroids , and azathioprine . Seventy-two percent of patients receiving OKT3 prophylaxis were rejection free in the first 14 days compared to 41 % in the cyclosporine group ( P=0.02 ) . However , after 14 days through a mean of 6.3 months , the overall incidence of rejection did not differ between the two groups ( 74 % for the cyclosporine group and 48 % for the OKT3 group ) . There was no increase in the rate of infectious complications noted in the OKT3-treated group . Thirty-nine percent of the OKT3-treated patients developed anti-OKT3 antibodies . Eight patients in the OKT3 group required reuse of OKT3 for rejection . Six of these continued to have greater than 10 % CD3-positive cells with retreatment . Five were rescued successfully . With a mean survival of greater than 674±209 days in the OKT3-treated group and 626±242 days in the cyclosporine-treated group , no overall differences in graft and patient survival , liver function , renal function , late rejection incidence , or infectious complications were evident between the two groups . We conclude that OKT3 offers no long-term benefit compared to cyclosporine prophylaxis and should be reserved for treatment of rejection in patients in whom cyclosporine may be contraindicated The aim of this prospect i ve r and omized trial was to study the efficacy and safety of tacrolimus monotherapy ( TACRO ) and compare it with our st and ard treatment of tacrolimus plus steroids ( TACRO + ST ) after liver transplant ( LT ) . Furthermore , the impact of steroid-free immunosuppression on outcome of hepatitis C virus ( HCV ) was analysed . Between 1998 and 2000 , 60 patients ( mean age : 57 years ) were included in the study and r and omized to receive TACRO ( n = 28 ) or TACRO + ST ( n = 32 ) . Indication for LT was postnecrotic cirrhosis in all cases ( 58.3 % were HCV-positive ) . Mean follow-up was 44 months . Survival , incidence of rejection , infection and side-effects were compared between the two groups . In patients with HCV infection , incidence and severity of acute hepatitis C , long-term outcome of recurrent hepatitis C and survival were studied in an intention-to-treat analysis or in the real group analysis ( real-TACRO versus real-TACRO + ST ) . Patient survival at 1 , 3 and 5 years , tacrolimus pharmacokinetics , incidence of rejection infections and side-effects were similar . In patients with HCV , the incidence and severity of graft hepatitis C tended to be lower in TACRO ( 47 % ) compared with TACRO + ST ( 67 % ) ( P = NS ) , and also in real-TACRO ( 42 % ) compared with real-TACRO + ST ( 61 % ) ( P = NS ) . A poor outcome considered as evolution to cirrhosis at 3 years was observed in one ( 9 % ) living patient in real-TACRO and nine ( 45 % ) in real-TACRO + ST ( P = 0.04 ) . Patient survival at 1 , 3 and 5 years was 92 % , 92 % and 73 % for real-TACRO and 78 % , 61 % and 51 % for real TACRO + ST ( P = 0.07 ) . Steroid-free immunosuppression appears to be safe and efficacious . The main advantage of this regimen could be in HCV patients , as recurrence of hepatitis in the graft was less severe in the group of patients in whom steroids could be avoided completely The 1‐year results of the tacrolimus versus microemulsified cyclosporin ( TMC ) study found a benefit with tacrolimus immunosuppression after primary liver transplants in adults with respect to freedom from graft loss and immunological failure . The integrity of the r and omization process was preserved for a further 2 years for post study surveillance . The data after 3 years confirms the significant difference between tacrolimus and cyclosporin with tacrolimus less likely to meet the composite primary endpoint ( log rank p = 0.01 ; relative risk 0.75 ; 95 % CI 0.60–0.95 ; p = 0.016 ) . However , freedom from death or retransplantation no longer achieves statistical significance ( relative risk 0.79 ; 95 % CI 0.62–1.02 ; p = 0.065 ) . A total of 62.1 % of patients r and omized to tacrolimus were alive at 3 years with their original graft and still on their allocated study medication , as compared with only 41.6 % in the cyclosporin limb ( p < 0.001 ) . No difference was detected between tacrolimus and cyclosporin in hepatitis‐C‐positive patients with the available data . The TMC study confirms after 3 years of follow‐up the benefits of tacrolimus‐based immunosuppression over cyclosporin using C0 monitoring We studied whether the use of sirolimus with reduced‐dose tacrolimus , as compared to st and ard‐dose tacrolimus , after liver transplantation is safe , tolerated and efficacious . In an international multicenter , open‐label , active‐controlled r and omized trial ( 2000–2003 ) , adult primary liver transplant recipients ( n = 222 ) were r and omly assigned immediately after transplantation to conventional‐dose tacrolimus ( trough : 7–15 ng/mL ) or sirolimus ( loading dose : 15 mg , initial dose : 5 mg titrated to a trough of 4–11 ng/mL ) and reduced‐dose tacrolimus ( trough : 3–7 ng/mL ) . The study was terminated after 21 months due to imbalance in adverse events . The 24‐month cumulative incidence of graft loss ( 26.4 % vs. 12.5 % , p = 0.009 ) and patient death ( 20 % vs. 8 % , p = 0.010 ) was higher in subjects receiving sirolimus . A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm ( 8 % vs. 3 % , p = 0.065 ) . The incidence of sepsis was higher in the sirolimus arm ( 20.4 % vs. 7.2 % , p = 0.006 ) . Rates of acute cellular rejection were similar between the two groups . Early use of sirolimus using a loading dose followed by maintenance doses and reduced‐dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss , death and sepsis when compared to the use of conventional‐dose tacrolimus alone Cyclosporine is an immunosuppressive agent widely used in the management of liver transplant recipients . Cyclosporine has been shown to have antiviral activities against HIV , herpes simplex , and vaccinia viruses . The aim of this study was to determine the effect of Cyclosporine in viral clearance in the liver transplant recipients during therapy with combination of interferon and ribavirin , and to determine the anti-viral potential of Cyclosporine in vitro . Immunosuppression consisted of either Cyclosporine or Tacrolimus-based therapy . Both groups received therapy with interferon and ribavirin for 48 weeks when evidence of progressive histologic disease was determined . We found that subjects on Cyclosporine-based immunosuppression ( n = 56 ) had a higher sustained virological response of 46 % compared to 27 % in the patients on Tacrolimus-based therapy ( n = 59 , P = 0.03 ) . In vitro studies were performed to evaluate the antiviral effect of Cyclosporine in the replicon system . These studies showed that Cyclosporine inhibits hepatitis C viral replication in a dose-dependent manner . Combination of Cyclosporine with interferon showed additive effect , and its function is independent of interferon signaling pathways . In conclusion , Cyclosporine may offer an advantage to Tacrolimus in those patients undergoing interferon-based therapy and should be studied in a prospect i ve r and omized trial A group of 52 liver transplant patients was prospect ively r and omized to receive prophylactic immunosuppressive therapy consisting of either Orthoclone OKT3 for 14 days , azathioprine , and steroids ( 25 patients ) ; or cyclosporine , azathioprine , and steroids ( 27 patients ) . The groups were similarly matched for age , diagnosis , and Child 's classification . The patients were studied to determine the effect of these two regimens on the incidence of rejection , infection , renal dysfunction , and mortality . Seven rejection episodes , as determined by clinical and histological criteria , occurred in seven of 25 patients ( 28 % ) receiving OKT3 compared with 18 episodes in 27 patients ( 67 % ) receiving cyclosporine during the first 14 days after transplantation ( P less than 0.02 ) . In 20 % of the OKT3 patients , CD3 + levels of greater than 10 % developed during therapy , and 16 % of the patients developed anti-OKT3 antibodies during OKT3 treatment . Five patients were retreated with OKT3 for steroid-resistant acute rejection episodes ; all had resolution of the rejection episode . Infectious complications were similar in each group . Renal function , as measured by serum creatinine , was significantly better with OKT3 than with cyclosporine ( P less than 0.003 ) at 14 days . We conclude that prophylactic OKT3 is effective in reducing the number of early rejection episodes after liver transplantation ; after 14 days the incidence of rejection is similar ; reuse of OKT3 has been successful in liver transplant patients ; infectious complications are similar between OKT3 and cyclosporine ; and OKT3 preserves renal function better than cyclosporine and is thus indicated in patients with compromised preoperative renal function The feasibility of de novo everolimus without calcineurin inhibitor ( CNI ) therapy following liver transplantation was assessed in a multicenter , prospect i ve , open‐label trial . Liver transplant patients were r and omized at 4 weeks to start everolimus and discontinue CNI , or continue their current CNI‐based regimen . The primary endpoint was adjusted estimated GFR ( eGFR ; Cockcroft‐Gault ) at month 11 postr and omization . A 24‐month extension phase followed 81/114 ( 71.1 % ) of eligible patients to month 35 postr and omization . The adjusted mean eGFR benefit from r and omization to month 35 was 10.1 mL/min ( 95 % confidence interval [ CI ] −1.3 , 21.5 mL/min , p = 0.082 ) in favor of CNI‐free versus CNI using Cockcroft‐Gault , 9.4 mL/min/1.73 m2 ( 95 % CI −0.4 , 18.9 , p = 0.053 ) with Modification of Diet in Renal Disease ( four‐variable ) and 9.5 mL/min/1.73 m2 ( 95 % CI −1.1 , 17.9 , p = 0.028 ) using Nankivell . The difference in favor of the CNI‐free regimen increased gradually over time due to a small progressive decline in eGFR in the CNI cohort despite a reduction in CNI exposure . Biopsy‐proven acute rejection , graft loss and death were similar between groups . Adverse events led to study drug discontinuation in five CNI‐free patients and five CNI patients ( 12.2 % vs. 12.5 % , p = 1.000 ) during the extension phase . Everolimus‐based CNI‐free immunosuppression is feasible following liver transplantation and patients benefit from sustained preservation of renal function versus patients on CNI for at least 3 years Objectives Chronic kidney disease is frequent in patients after orthotopic liver transplantation ( OLT ) and has impact on survival . Patients receiving calcineurin inhibitors ( CNI ) are at increased risk to develop impaired renal function . Early CNI reduction and concomitant use of mycophenolat mofetil ( MMF ) has been shown to improve renal function . Methods The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate ( GFR ) . 21 patients [ GFR 44.9 ± 9.9 mL/min/1.73 m2 measured by 99m-Tc-DTPA-clearance , serum creatinine ( SCr ) 1.5 ± 0.42 mg/dL ] were r and omized either to exchange CNI for 10 mg prednisone ( group 1 ; n = 8) or to receive CNI at 25 % of the initial dose ( group 2 ; n = 13 ) each in combination with 1000 mg MMF b.i.d . Results At month 12 mean SCr ( -0.3 ± 0.4 mg/dL , p = 0.031 ) and GFR improved ( 8.6 ± 13.1 mL/min/1.73 m2 , p = 0.015 ) in group 2 but remained unchanged in group 1 . Main side effects were gastroinstestinal symptoms ( 14.3 % ) and infections ( 4.8 % ) . Two biopsy proven , steroid-responsive rejections occurred . In group 1 mean diastolic blood pressure ( BP ) increased by 11 ± 22 mmHg ( p = 0.03 ) . Conclusions Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT . Addition of steroids result ed in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function Objective Early results of a r and omised trial showed reduced fibrosis due to recurrent HCV hepatitis with tacrolimus triple therapy ( TT ) versus monotherapy ( MT ) following transplantation for HCV cirrhosis . We evaluated the clinical outcomes after a median 8 years of follow-up , including differences in fibrosis assessed by collagen proportionate area ( CPA ) . Design 103 consecutive liver transplant recipients with HCV cirrhosis receiving cadaveric grafts were r and omised to tacrolimus MT ( n=54 ) or TT ( n=49 ) with daily tacrolimus ( 0.1 mg/kg divided dose ) , azathioprine ( 1 mg/kg ) and prednisolone ( 20 mg ) , the last tailing off to zero by 6 months . Both groups had serial transjugular biopsies with hepatic venous pressure gradient ( HVPG ) measurement . Time to reach Ishak stage 4 was the predetermined endpoint . CPA was measured in all biopsies . Factors associated with HCV recurrence were evaluated . Clinical decompensation was the first occurrence of ascites/hydrothorax , variceal bleeding or encephalopathy . Results No significant preoperative , peri-operative or postoperative differences between groups were found . During 96 months median follow-up , stage 4 fibrosis was reached in 19 MT/11 TT with slower fibrosis progression in TT ( p=0.009 ) . CPA at last biopsy was 12 % in MT and 8 % in TT patients ( p=0.004 ) . 14 MT/ three TT patients reached HVPG≥10 mm Hg ( p=0.002 ) ; 10 MT/three TT patients , decompensated . Multivariately , allocated MT ( p=0.047 , OR 3.23 , 95 % CI 1.01 to 10.3 ) was independently associated with decompensation : 14 MT/ seven TT died , and five MT/ four TT were retransplanted . Conclusions Long term immunosuppression with tacrolimus , azathioprine and short term prednisolone in HCV cirrhosis recipients result ed in slower progression to severe fibrosis assessed by Ishak stage and CPA , less portal hypertension and decompensation , compared with tacrolimus alone . IS RCT N94834276 —R and omised study for immunosuppression regimen in liver transplantation This exploratory phase II study evaluated the safety and efficacy of belatacept in de novo adult liver transplant recipients . Patients were r and omized ( N = 260 ) to one of the following immunosuppressive regimens : ( i ) basiliximab + belatacept high dose [ HD ] + mycophenolate mofetil ( MMF ) , ( ii ) belatacept HD + MMF , ( iii ) belatacept low dose [ LD ] + MMF , ( iv ) tacrolimus + MMF , or ( v ) tacrolimus alone . All received corticosteroids . Demographic characteristics were similar among groups . The proportion of patients who met the primary end point ( composite of acute rejection , graft loss , death by month 6 ) was higher in the belatacept groups ( 42–48 % ) versus tacrolimus groups ( 15–38 % ) , with the highest number of deaths and grafts losses in the belatacept LD group . By month 12 , the proportion surviving with a functioning graft was higher with tacrolimus + MMF ( 93 % ) and lower with belatacept LD ( 67 % ) versus other groups ( 90 % : basiliximab + belatacept HD ; 83 % : belatacept HD ; 88 % : tacrolimus ) . Mean calculated GFR was 15–34 mL/min higher in belatacept‐treated patients at 1 year . Two cases of posttransplant lymphoproliferative disease and one case of progressive multifocal leukoencephalopathy occurred in belatacept‐treated patients . Follow‐up beyond month 12 revealed an increase in death and graft loss in another belatacept group ( belatacept HD ) , after which the study was terminated Allograft reinfection with hepatitis C virus ( HCV ) occurs universally in liver transplant recipients . Corticosteroids can contribute to HCV recurrence . This r and omized study evaluated HCV recurrence in HCV-positive liver allograft recipients using steroid-free immunosuppression . All patients received tacrolimus ( TAC ) at an initial dose of 0.10–0.15 mg/kg . The steroid-free arm ( TAC/daclizumab ( TAC/DAC , n = 67 ) ) received daclizumab induction , and the steroid arm ( TAC/steroid ( TAC/STR , n = 68 ) ) received a steroid bolus ( ≤ 500 mg ) followed by 15–20 mg/day with discontinuation after month 3 . Median HCV viral load at month 12 , the primary endpoint , was similar at 5.46 ( 0.95–6.54 ) IU/mL with TAC/DAC and 5.91 ( 0.95–6.89 ) IU/mL with TAC/STR . Small numerical differences in the estimated rate of freedom from HCV recurrence ( 19.1 versus 13.8 % ) and freedom from biopsy proven rejection ( 78.4 versus 66.1 % ) were observed between TAC/DAC and TAC/STR . Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR ( 83.1 versus 95.5 % ; 95 % CI , −0.227 to −0.019 % ) , and graft survival was numerically lower ( 80.1 versus 91.1 % , P = NS ) . Completion rates ( 45 versus 82 % ) indicated poorer tolerability with TAC/DAC than with TAC/STR . Steroid-free immunosuppression had no real impact on HCV viral load . HCV recurrence was higher with TAC/STR . Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation ( LTx ) c and i date s with hepatocellular carcinoma ( HCC ) . Methods In a prospect ive-r and omized open-label international trial , 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor – free immunosuppression were r and omized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor – free immunosuppression ( group A : 264 patients ) or a group incorporating sirolimus ( group B : 261 ) . The primary endpoint was recurrence-free survival ( RFS ) ; intention-to-treat ( ITT ) analysis was conducted after 8 years . Overall survival ( OS ) was a secondary endpoint . Results Recurrence-free survival was 64.5 % in group A and 70.2 % in group B at study end , this difference was not significant ( P = 0.28 ; hazard ratio [ HR ] , 0.84 ; 95 % confidence interval [ 95 % CI ] , 0.62 ; 1.15 ) . In a planned analysis of RFS rates at yearly intervals , group B showed better outcomes 3 years after transplantation ( HR , 0.7 ; 95 % CI , 0.48 - 1.00 ) . Similarly , OS ( P = 0.21 ; HR , 0.81 ; 95 % CI , 0.58 - 1.13 ) was not statistically better in group B at study end , but yearly analyses showed improvement out to 5 years ( HR , 0.7 ; 95 % CI , 0.49 - 1.00 ) . Interestingly , subgroup ( Milan Criteria -based ) analyses revealed that low-risk , rather than high-risk , patients benefited most from sirolimus ; furthermore , younger recipients ( age ⩽60 ) also benefited , as well sirolimus monotherapy patients . Serious adverse event numbers were alike in groups A ( 860 ) and B ( 874 ) . Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years . However , a RFS and OS benefit is evident in the first 3 to 5 years , especially in low-risk patients . This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC Background Introduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients . However , long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure , neurotoxicity , de novo malignancies , recurrence of hepatitis C viral ( HCV ) infection and hepatocellular carcinoma . Several studies have shown that everolimus has the potential to provide protection against viral replication , malignancy , and progression of fibrosis , as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy . The Hephaistos study evaluates the beneficial effects of early initiation of everolimus in de novo liver transplant recipients . Methods / Design Hephaistos is an ongoing 12-month , multi-center , open-label , controlled study aim ing to enroll 330 de novo liver transplant recipients from 15 centers across Germany . Patients are r and omized in a 1:1 ratio ( 7–21 days post-transplantation ) to receive everolimus ( trough levels 3–8 ng/mL ) with reduced tacrolimus ( trough levels < 5 ng/mL ) , or st and ard tacrolimus ( trough levels 6–10 ng/mL ) after entering a run-in period ( 3–5 days post-transplantation ) . In the run-in period , patients are treated with induction therapy , mycophenolate mofetil , tacrolimus , and corticosteroids according to local practice . R and omization is stratified by HCV status and model of end-stage liver disease scores at transplantation . The primary objective of the study is to exhibit superior renal function ( estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease (MDRD)-4 formula ) with everolimus plus reduced tacrolimus compared to st and ard tacrolimus at Month 12 . Other objectives are : to assess the incidence of treated biopsy-proven acute rejection , graft loss , or death ; the incidences of components of the composite efficacy endpoint ; renal function via estimated glomerular filtration rate using various formulae ( MDRD-4 , Nankivell , Cockcroft-Gault , chronic kidney disease epidemiology collaboration and Hoek formulae ) ; the incidence of proteinuria ; the incidence of adverse events and serious adverse events ; the incidence and severity of cytomegalovirus and HCV infections and HCV-related fibrosis . Discussion This study aims to demonstrate superior renal function , comparable efficacy , and safety in de novo liver transplant recipients receiving everolimus with reduced tacrolimus compared with st and ard tacrolimus . This study also evaluates the antiviral benefit by early initiation of everolimus . Trial registration NCT01551212 DIAMOND : multicenter , 24‐week , r and omized trial investigating the effect of different once‐daily , prolonged‐release tacrolimus dosing regimens on renal function after de novo liver transplantation . Arm 1 : prolonged‐release tacrolimus ( initial dose 0.2mg/kg/day ) ; Arm 2 : prolonged‐release tacrolimus ( 0.15–0.175mg/kg/day ) plus basiliximab ; Arm 3 : prolonged‐release tacrolimus ( 0.2mg/kg/day delayed until Day 5 ) plus basiliximab . All patients received MMF plus a bolus of corticosteroid ( no maintenance steroids ) . Primary endpoint : eGFR ( MDRD4 ) at Week 24 . Secondary endpoints : composite efficacy failure , BCAR and AEs . Baseline characteristics were comparable . Tacrolimus trough levels were readily achieved posttransplant ; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3 . eGFR ( MDRD4 ) was higher in Arms 2 and 3 versus 1 ( p = 0.001 , p = 0.047 ) . Kaplan – Meier estimates of composite efficacy failure‐free survival were 72.0 % , 77.6 % , 73.9 % in Arms 1–3 . BCAR incidence was significantly lower in Arm 2 versus 1 and 3 ( p = 0.016 , p = 0.039 ) . AEs were comparable . Prolonged‐release tacrolimus ( 0.15–0.175mg/kg/day ) immediately posttransplant plus basiliximab and MMF ( without maintenance corticosteroids ) was associated with lower tacrolimus exposure , and significantly reduced renal function impairment and BCAR incidence versus prolonged‐release tacrolimus ( 0.2mg/kg/day ) administered immediately posttransplant . Delayed higher‐dose prolonged‐release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration , but BCAR incidence was comparable In a prospect i ve , multicenter , open‐label study , de novo liver transplant patients were r and omized at day 30±5 to ( i ) everolimus initiation with tacrolimus elimination ( TAC Elimination ) ( ii ) everolimus initiation with reduced‐exposure tacrolimus ( EVR+Reduced TAC ) or ( iii ) st and ard‐exposure tacrolimus ( TAC Control ) . R and omization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy‐proven acute rejection ( tBPAR ) . EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint ( tBPAR , graft loss or death at 12 months posttransplantation ) : 6.7 % versus 9.7 % ( −3.0 % ; 95 % CI −8.7 , 2.6 % ; p<0.001 for noninferiority [ 12 % margin ] ) . tBPAR occurred in 2.9 % of EVR+Reduced TAC patients versus 7.0 % of TAC Controls ( p = 0.035 ) . The change in adjusted estimated GFR from r and omization to month 12 was superior with EVR+Reduced TAC versus TAC Control ( difference 8.50 mL/min/1.73 m2 , 97.5 % CI 3.74 , 13.27 mL/min/1.73 m2 , p<0.001 for superiority ) . Drug discontinuation for adverse events occurred in 25.7 % of EVR+Reduced TAC and 14.1 % of TAC Controls ( relative risk 1.82 , 95 % CI 1.25 , 2.66 ) . Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 ( 95 % CI 1.03 , 3.00 ) . Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function , compared to a st and ard tacrolimus exposure regimen 12 months after liver transplantation A multicenter r and omized trial was performed to compare two immunosuppressive protocol s after first ABO-compatible liver transplantation . Forty six patients were r and omized to a 14-day treatment with Orthoclone ( OKT3 ) in association with steroids and azathioprine , cyclosporine being progressively introduced on day 11 posttransplant . Fifty patients were r and omized to a st and ard protocol of cyclosporine with steroids and azathioprine . Minimum follow-up was 1 year and graft and patient survivals were up date d for the purpose of the study . The cumulative 1-year incidence of acute rejection tended to be greater in the cyclosporine group ( 75 % ) than in the OKT3 group ( 67 % ) , especially when patients who did not receive full-course treatment with OKT3 were excluded ( 59 % ) . Renal function was better preserved during the first two postoperative weeks in the OKT3 group than in the control group but plasma creatinine levels were comparable in both groups thereafter . The incidence of severe infections was lower in the OKT3 group ( 13.6 % ) than in the cyclosporine group ( 32 % ) . The 4-year incidences of patient and graft survival in the OKT3 group ( 69 % and 61 % , respectively ) were not different from those in the cyclosporine group ( 62 % versus 54 % , respectively ) . Thus this prospect i ve trial shows that OKT3 immunoprophylaxis is a safe alternative to cyclosporine immunoprophylaxis in unselected recipients of a first liver graft With the aim of assessing whether fenoldopam can help to preserve renal function after liver transplantation , we r and omized 140 consecutive recipients with comparable preoperative renal function to receive fenoldopam 0.1 microg/kg/minute ( group F , 46 patients ) , dopamine 3 microg/kg/minute ( group D , 48 patients ) , or placebo ( group P , 46 patients ) from the time of anesthesia induction to 96 hours postoperatively . There were no differences between the groups in intraoperative urinary output or furosemide administration ( both P = .1 ) . Daily recordings made during the first 4 postoperative days revealed no significant differences in urinary output ( P = .1 ) , serum creatinine ( P = .5 ) , the incidence of renal insufficiency ( P = .7 ) , the need for loop diuretics ( P = .9 ) or vasoactive drugs ( P = .8 ) . In comparison with preoperative levels , creatinine clearance at the end of the study in the patients receiving fenoldopam remained substantially unchanged , whereas it decreased by 39 and 12.3 % , respectively , in the subjects receiving placebo or dopamine ( P < .001 ) ; blood cyclosporine A ( CsA ) levels were similar in the 3 groups ( P = .1 ) . Three subjects died in the intensive care unit ( 1 in each group , P = .9 ) , 2 of them had renal failure . In conclusion , our results confirm the inefficacy of dopamine in preventing or limiting early renal dysfunction after liver transplantation , and suggest that fenoldopam may preserve creatinine clearance by counterbalancing the renal vasoconstrictive effect of CsA , as it has been reported in previous experimental studies Abstract : Background : This is a 4‐yr follow‐up of a trial using mycophenolate mofetil ( MMF ) induction in orthotopic liver transplantation ( OLT ) . The goal of this study was to evaluate a multidrug approach that would reduce both early and long‐term morbidity related to immunosuppression while maintaining an acceptable freedom from rejection Background : Minimal immunosuppression ( IS ) is desirable in organ transplantation to reduce side effects and to promote the process of tolerance induction . Material and Methods : Between February 2000 and September 2004 , 156 adults ( > 15 years old ) receiving a primary liver graft were enrolled in a prospect i ve , r and omized , double-blind , placebo-controlled , investigator-driven single-center study comparing tacrolimus (TAC)-placebo ( PL ) and TAC-low-dose , short-term ( 64 days ) steroid ( ST ) IS . There were no exclusion criteria at moment of r and omization . All patients had a 12-month follow-up ( range , 12–84 ) . Results : Three- and 12-month patient survival rates were 93.6 % and 87.2 % in the TAC-PL group and 98.7 % and 94.7 % in TAC-ST group ( P = 0.096 and P = 0.093 , respectively ) . Three- and 12-month graft survival rates were 92.3 % and 85.9 % versus 97.4 % and 92.3 % ( P = 0.14 and 0.13 , respectively ) . By 3 and 12 months , rejection treatment had been given in 20.5 % ( 16 pts ) and 23 % ( 18 pts ) of TAC-PL patients and in 12.7 % ( 10 pts ) and 20.5 % ( 16 pts ) of TAC-ST patients ( P = 0.20 and 0.54 ) . Corticosteroid-resistant rejection ( CRR ) at 3 and 12 months was recorded in 12.8 % ( 10 pts ) of TAC-PL patients and 3.8 % ( 3 pts ) of TAC-ST patients ( P = 0.04 ) . When considering the 145 patients transplanted without artificial organ support ( n = 145 ) , CRR at 3 and 12 months was recorded in 8.8 % ( 6/68 pts ) of TAC-PL patients and in 3.9 % ( 3/77 pts ) of TAC-ST patients ( P = 0.22 ) . Vanishing bile duct syndrome was diagnosed in 1 ( 1.2 % ) TAC-PL patient and 4 ( 5.1 % ) TAC-ST patients ( P = 0.17 ) . By 1 year , 78.2 % ( 61/78 ) of TAC-PL patients and 82 % ( 64/78 ) of TAC-ST patients were on TAC monotherapy ( P = 0.54 ) . When considering 67 TAC-PL and 74 TAC-ST survivors , rates of monotherapy were 91 % ( 61 pts ) and 86.5 % ( 64 pts ) ( P = 0.39 ) . At 1 year , 62.5 % ( 42 pts ) of TAC-PL survivors and 64.9 % ( 48 pts ) of TAC-ST survivors were on low-dosage ( < 6 ng/mL ) TAC monotherapy ( P 0.79 ) . Conclusion : TAC monotherapy can be achieved safely without compromising graft nor patient survival in a primary , even unselected , adult liver transplant population . The higher incidence of early CRR in the TAC-PL group related to the significantly higher number of patients transplanted while being on artificial organ support . In such condition , this monodrug immunosuppressive strategy needs to be adapted . TAC monotherapy strategy should lay the basis for further large scale minimization studies in liver transplantation Background . Hepatitis C virus ( HCV ) recurrence in HCV+ liver transplant recipients is almost inevitable and may be promoted by immunosuppression . We compared the amount of liver damage with regard to usage of steroids and basiliximab . Methods . A total of 140 HCV+ adult liver transplant recipients were r and omly allocated to basiliximab+steroids or basiliximab+placebo ( plus cyclosporine and azathioprine ) . Primary endpoint : hepatitis C histological recurrence ( liver damage as for Ishak grading score ≥8 by biopsy at 12 months ) ; secondary endpoints : treatment failure ( death , graft loss , patient withdrawal ) , biopsy proven acute rejection ( BPAR ) , treated acute rejection ( tAR ) , allograft and patient survival rates at 12 months . Results . Any significant difference has been observed in the 12-month hepatitis C histological recurrence rate ( 41.2 % basiliximab+steroids , 37.5 % basiliximab+placebo , P=0.354 ) . The treatment failure rate was significantly higher in basiliximab+steroids ( 28.8 % ) than in basiliximab+placebo ( 15.6 % ) , P=0.03 ; the combination test for the evaluation of the joint hypothesis result ed in a borderline nonsignificant overall result ( P=0.059 ) . BPAR rate was significantly lower in the group treated with steroids ( 24.3 % basiliximab+steroids , 39.4 % basiliximab+placebo , P=0.04 ) , while the tAR rate was similar ( 29.7 % basiliximab+steroids and 37.9 % basiliximab+placebo ) . Any significant differences in 1-year graft and patient survival rates have been observed ( 72.9 % and 84.8 % basiliximab+steroids ; 81.5 % and 89.0 % basiliximab+placebo ) . Conclusions . Results suggest that steroid-free therapy is associated with a significantly lower treatment failure rate , although histological recurrence rate of hepatitis C is similar in the two groups . This benefit is not offset by an evident increase in graft rejection rate requiring treatment The LIS2 T study was an open-label , multicenter study in which recipients of a primary liver transplant were r and omized to cyclosporine microemulsion ( CsA-ME ) ( Neoral ) ( n = 250 ) ( monitoring of blood concentration at 2 hours postdose ) C2 or tacrolimus ( n = 245 ) ( monitoring of trough drug blood level [ predose ] ) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months . All patients received steroids with or without azathioprine . At 12 months , 85 % of CsA-ME patients and 86 % of tacrolimus patients survived with a functioning graft ( P not significant ) . Efficacy was similar in deceased- and living-donor recipients . Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME ( 5/88 , 6 % ) than with tacrolimus ( 14/85 , 16 % ) ( P < 0.03 ) . Recurrence of hepatitis C virus in liver grafts was similar in each group . Based on biopsies driven by clinical events , the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME ( 100 + /- 50 days ) than with tacrolimus ( 70 + /- 40 days ) ( P < 0.05 ) . Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus . More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months ( 13 % vs. 5 % , P < 0.01 ) . Of patients who were diabetic at baseline , more tacrolimus-treated individuals required anti-diabetic treatment at 12 months ( 70 % vs. 49 % , P = 0.02 ) . Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups . In conclusion , the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months , and renal function is similar . More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline Background . Blockade of costimulation and adhesion signaling is an attractive approach to interfere with graft rejection Methods . Between January 1997 and May 1999 , forty adults having benign liver diseases were included in a prospect i ve , r and omized study comparing tacrolimus plus low-dose short-term steroids without ( n=20 , TAC group ) or with a 10-day course of antihuman CD2 monoclonal antibody ( n=20 , BTI group ) . Results . At day 7 , histological rejection expressed by mean Banff scores ( 2.3±1.6 vs. 5.4±1.6 in the TAC group ; P < 0.0001 ) and incidence of moderate to severe rejection ( score ≥6 ) ( 0 vs. 10 [ 50 % ] in the TAC group ; P<0.001 ) were significantly lower in the BTI group . Rejection was treated in 10 % ( two patients ) of BTI patients during the first 3 months and in 15 % during the whole follow-up and in 25 % ( five patients ) of TAC patients ( P = NS ) . None of the BTI- patients presented with an adverse event . Three-month , 1-year , and 5-year actual patient survival rates were 100 % , 95 % , and 95 % in the BTI group and 100 % , 100 % , and 85 % in the TAC group . Graft survival rates were 100 % , 90 % , and 90 % in the BTI group and 95 % , 95 % , and 80 % in the TAC group ( P = NS ) . The mAb had no negative impact on infectious or tumor events . Conclusions . Antihuman CD2 monoclonal antibody is a safe immunosuppressive drug which has a favorable impact on early immunological follow-up of liver transplanted patients . The antibody had no impact on late patient and graft survival A r and omized , double-blind , dose-escalation study evaluated the safety and efficacy of hepatitis C virus (HCV)-Ab(XTL)68 , a neutralizing , high-affinity , fully human , anti-E2 monoclonal antibody , in 24 HCV-positive patients undergoing liver transplantation . HCV-Ab(XTL)68 or placebo was administered at doses from 20 - 240 mg as 2 - 4 infusions during the first 24 hours after transplantation , followed by daily infusions for 6 days , weekly infusions for 3 weeks , and either 2 or 4 weekly infusions for 8 weeks . Serum concentrations of total anti-E2 obtained during daily infusions of 120 - 240 mg HCV-Ab(XTL)68 were 50 - 200 microg/mL above concentrations in the placebo group . Median serum concentration of HCV RNA dropped below baseline in all groups immediately after transplantation . On day 2 , median change from baseline in HCV RNA was -1.8 and -2.4 log in the 120-mg and 240-mg groups , respectively , compared with -1.5 log with placebo . The difference was lost after day 7 when the dosing frequency was reduced . The coincidence of increases in anti-E2 with decreases in HCV RNA concentration indicate that the dose-related changes in HCV RNA concentration were a result of HCV-Ab(XTL)68 administration in the 120- and 240-mg groups . The overall incidence of nonfatal serious adverse events was higher with placebo ( 60 % ) vs. all active treatments combined ( 42 % ) . In conclusion , HCV-Ab(XTL)68 may decrease serum concentrations of HCV RNA in patients after liver transplantation . Studies evaluating more frequent daily dosing at doses > 120 mg are necessary to investigate sustained viral suppression in this population We report a multicenter , prospect i ve , r and omized , open‐label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients . Adult patients with good renal function undergoing primary liver transplant were r and omized to either : group A ( st and ard‐dose tacrolimus [ target trough levels > 10 ng/mL ] and corticosteroids ; n = 183 ) ; group B ( mycophenolate mofetil [ MMF ] 2g/day , reduced‐dose tacrolimus [ target trough levels ≤8 ng/mL ] , and corticosteroids ; n = 170 ) ; group C ( daclizumab induction , MMF , reduced‐dose tacrolimus delayed until the fifth day posttransplant and corticosteroids , n = 172 ) . The primary endpoint was change from baseline in estimated glomerular filtration rate ( eGFR ) at 52 weeks . The eGFR decreased by 23.61 , 21.22 and 13.63 mL/min in groups A , B and C , respectively ( A vs C , p = 0.012 ; A vs B , p = 0.199 ) . Renal dialysis was required less frequently in group C versus group A ( 4.2 % vs. 9.9 % ; p = 0.037 ) . Biopsy‐proven acute rejection rates were 27.6 % , 29.2 % and 19.0 % , respectively . Patient and graft survival was similar . In conclusion , daclizumab induction , MMF , corticosteroids and delayed reduced‐dose tacrolimus was associated with less nephrotoxicity than therapy with st and ard‐dose tacrolimus and corticosteroids without compromising efficacy or tolerability REFINE was a 12‐month , prospect i ve , open‐label study in 356 patients receiving de novo liver transplantation for hepatitis C virus ( HCV ) cirrhosis , r and omized to cyclosporine A ( CsA ) or tacrolimus with ( i ) no steroids , IL‐2 receptor antibody induction and mycophenolic acid , or ( ii ) slow steroid tapering . The primary analysis population based on availability of liver biopsies comprised 165 patients ( 88 CsA , 77 tacrolimus ) . There was no difference in the primary endpoint , fibrosis stage ≥2 at 12 months , which occurred in 63/88 CsA‐treated patients ( 71.6 % ) and 52/77 tacrolimus‐treated patients ( 67.5 % ) ( odds ratio [ OR ] 1.11 ; 95 % CI 0.56 , 2.21 ; p = 0.759 ) . Similarly , no significant between‐group difference occurred at month 24 ( OR 1.15 ; 95 % CI 0.47 , 2.80 ; p = 0.767 ) . Among steroid‐free patients , fibrosis score ≥2 was significantly less frequent with CsA versus tacrolimus at month 12 ( 7/37 [ 18.9 % ] vs. 16/38 [ 42.1 % ] ; p = 0.029 ) . HCV viral load was similar in both the tacrolimus‐ and CsA‐treated cohorts . Mean blood glucose was significantly higher with tacrolimus from day 15 onward . Biopsy‐proven acute rejection , graft loss and death were similar . These results showed no differences in posttransplant HCV‐induced liver fibrosis between patients treated with CsA or tacrolimus in steroid‐containing regimens , whereas CsA in steroid‐free protocol s was associated with reduced severity of fibrosis progression at 1 year posttransplant BACKGROUND Immunosuppression in patients with hepatitis C virus ( HCV ) following orthotopic liver transplantation can lead to significant increases in serum viral loads . Our aim was to analyze the effect of a r and omized study of two immunosuppressive agents ( tacrolimus vs. microemulsion cyclosporine ) on the outcome of HCV patients following orthotopic liver transplantation . METHODS From December 1995 to September 1996 , 50 adult patients transplanted for HCV cirrhosis were r and omly assigned to receive tacrolimus ( Prograf ) ( group 1 , 25 patients ) or microemulsion cyclosporine ( Neoral ) ( group 2 , 24 patients ) . All patients received alpha-interferon after transplantation , and the overall steroid doses were no different between the groups . Serum RNA levels were measured by signal amplification of Chiron . Biopsies were taken when transaminases were greater than 2x base line or when there was an inappropriate response to alterations in immunosuppression regimens . RESULTS There were more episodes of rejection in the Neoral group , but there were no differences in bacterial and viral infections , nor in the rate of HCV recurrence between the two groups . There were seven deaths in group 1 and eight in group 2 . Overall patient and graft survival rates in the Prograf and Neoral groups at 18 months were 72 and 68 % and 67 and 64 % , respectively . CONCLUSIONS ( a ) Both immunosuppression regimens had similar HCV recurrence rates ; ( b ) there were no differences in bacterial or opportunistic infections ; and ( c ) patient and graft survival was similar between the two groups The steroid-sparing effect and the use of concomitant medication during the treatment of liver transplant patients with the novel immunosuppressant FK 506 were evaluated within the European multicentre , r and omized , parallel-group study in liver transplantation . Patients undergoing primary liver transplantation were r and omized to treatment with FK 506 ( n = 267 ) or with a cyclosporin-based immunosuppressive regimen ( n = 273 ) . The total cumulative steroid usage was significantly reduced in the FK 506 treatment group , which is likely to have result ed from the lower incidence of acute rejection in these patients . The number of patients receiving antidiabetic , diuretic and antihypertensive therapy did not differ between the two treatment groups , even though the incidence of diabetes mellitus and oliguria was significantly higher in the FK 506 group . It can , therefore , be assumed that in a number of such cases the severity of these events was very mild necessitating no specific therapy The early safety and efficacy of tacrolimus after liver transplantation has been shown in two multicenter trials . Herein , we report our single-center long-term follow-up of a r and omized controlled trial . As part of a European multicenter trial , 121 patients entered the study at our institution and were r and omly assigned to receive either tacrolimus and steroids ( n=61 ) or a quadruple protocol ( n=60 ) using ciclosporin A , steroids , azathioprine , and antithymocyte globulin ( ATG ) . Twelve-year figures of patient survival were 74 % in the tacrolimus group and 66 % in the cyclosporine-based group . Graft survival after 12 years was 69 % in the tacrolimus group compared to 56 % in the cyclosporin-based group ( not significant , p=0.15 ) . The total rate of graft loss and retransplantation decreased significantly in the tacrolimus arm ( p<0.05 ) . De novo malignancies increased significantly in the ciclosporin-based group and dominated as single cause of death beyond 5 years posttransplant . The use of tacrolimus after liver transplantation result ed in a decreased rate of graft loss over the long-term . An increased number of de novo malignancies in the ciclosporin-based group may be attributable to the use of ATG as induction therapy This open , r and omized ( 1 : 1 ) , multicenter , 3-month study compared a dual tacrolimus plus steroids ( Tac / steroids ) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy ( Tac / Dac ) in adult liver transplant recipients . The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group . Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups ; mean whole-blood trough levels during month 3 were 10.9 ng/mL ( Tac / steroids ) and 10.6 ng/mL ( Tac / Dac ) . The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups : 26.5 % in the Tac / steroids group and 25.4 % in the Tac / Dac group ( P = .727 ) . However , the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group ( 6.3 vs. 2.8 % ; P = .027 ) . Kaplan-Meier estimates of graft survival ( 92.2 vs. 90.5 % ) and patient survival ( 94.5 vs. 93.7 % ) were similar in both groups . While also the overall adverse event profiles were similar , the incidences of diabetes mellitus ( 15.3 vs. 5.7 % , respectively ; P < .001 ) and cytomegalovirus infection ( 11.5 vs. 5.1 % , respectively ; P = .002 ) were higher in the Tac / steroids group compared with the Tac / Dac group . Mean cholesterol levels increased by 16 % in the Tac / steroids group , but were unchanged in the Tac / Dac group during the study . In conclusion , tacrolimus monotherapy following daclizumab induction is an effective and safe regimen , with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection , and a lower incidence of steroid-resistant acute rejection Acute hepatic allograft rejection occurs in approximately 50 % to 60 % of the patients undergoing liver transplantation . In this study , we compared the rate of acute rejection in liver transplant recipients r and omized in a double-blind comparative study to treatment with mycophenolate mofetil ( MMF ) or azathioprine ( AZA ) , both in combination with cyclosporine and corticosteroids . Five hundred sixty-five primary liver transplant recipients were r and omly assigned to treatment with MMF , 1 g twice daily intravenously followed by 1.5 g twice daily orally ( n = 278 ) , or AZA , 1.0 to 2.0 mg/kg/d intravenously followed by oral administration ( n = 287 ) , in combination with cyclosporine and corticosteroids . Patients were followed up for at least 1 year , and efficacy analysis was based on intent-to-treat methods . Acute rejection was defined according to the Banff histological criteria . The two study groups were balanced for demographic and clinical baseline characteristics . The incidence of acute rejection or graft loss was 47.7 % in the AZA patients and 38.5 % in the MMF patients ( P < .03 ) . The incidence of biopsy-proven and treated rejection censoring for graft loss was 40.0 % in the AZA group versus 31.0 % in the MMF group ( P < .06 ) . Steroid-resistant rejection requiring treatment with either OKT3 or antithymocyte globulin occurred in 8.2 % of AZA patients versus 3.8 % in MMF patients ( P < .02 ) . Patient and graft survival rates at 1 year posttransplantation were 85.4 % in the AZA group and 85.3 % in the MMF group ( P = not significant ) . MMF was superior to AZA in preventing acute rejection in the first 6 months posttransplantation . MMF and AZA were equivalent in preventing graft loss at 1 year , and the safety profiles between the two immunosuppressive agents were similar Two-hour postdose cyclosporine ( C2 ) monitoring is becoming an accepted method of therapeutic drug monitoring , although it is not known whether C2 monitoring is superior to tacrolimus (FK)-based immunosuppression . The purpose of this trial was to compare the safety , efficacy , and pharmacoeconomics of cyclosporine A ( CsA ) monitored by C2 levels versus FK monitored by trough levels in de novo liver transplant recipients . After informed consent , 60 de novo liver transplant recipients were r and omized in a 1:1 fashion to receive either FK ( trough , 6 - 10 ng/mL ) or CsA ( C2 , 600 - 1200 ng/mL ) and corticosteroids . The 2 groups were similar for gender , race , indication for liver disease , and age . At 1 year , patient survival was similar ( 93 % for FK versus 90 % for C2 ) . One patient in the FK arm was retransplanted because of recurrent hepatitis C virus ( HCV ) . Early acute rejection occurred in 27 % of FK-treated patients and 23 % of CsA-treated recipients [ P = not significant ( NS ) ] . Recurrent HCV occurred in 21 % of FK-treated patients and 61 % of CsA-treated patient ( P = 0.04 ) . The incidence of other infections , new onset diabetes mellitus , requirement for antihypertensives , and requirement for cholesterol medications were similar between the groups . Annual calcineurin inhibitor costs were lower in the C2 arm ( $ 5432 + /- 2091 for C2 versus $ 8291 + /- 3948 for FK , P = 0.001 ) . Annual pretransplant drug costs ( $ 2292 + /- 2331 for C2 versus $ 2831 + /- 2358 for FK , P = NS ) and 1-year posttransplant drug costs ( $ 17,214 + /- 16,600 for C2 versus $ 15,151 + /- 11,699 for FK , P = NS ) were similar . In conclusion , immunosuppression with CsA , monitored by C2 levels , is safe , effective , and economical in liver transplant recipients and provides immunosuppression at least equivalent to that of FK A prospect i ve trial was conducted to assess the efficacy of induction immunosuppression with antilymphocyte monoclonal antibodies in 129 primary liver transplant patients who were r and omly divided into three groups according to immunosuppression during the first 10 days post-OLT : triple drug therapy only ( TDIS : cy-closporine , steroids , azathioprine ) ( group I : n=42 ) ; TDIS with a 10-day course of OKT3 ( group II : n=44 ) ; and LO-Tact-1 ( anti-IL-2 receptor mAb ) ( group III : n=43 ) . Biopsy-proved acute rejection ( AR ) was treated using the same biopsy-guided protocol in the 3 groups . One-year patient survival rates were 67 % , 84 % , and 93 % in groups I , II , and III , respectively ( I vs. II , NS ; I vs. III , P=0.001 ; II vs. III , P=0.044 ) . Incidences of AR were studied in the subgroup of 100 patients who were exposed to the risk of developing rejection , with The efficacy and safety of FK 506 compared with cyclosporin were evaluated in a European multicentre study with primary liver transplant patients . The daily intravenous doses ranged from 0.15 to 15.9 mg and the daily oral doses from 0.5 to 30 mg . Trough concentrations of FK 506 in blood and plasma were determined by an enzyme immunoassay . Blood concentrations ranged from 0.5 to 391 ng/ml and from 0.5 to 616 ng/ml after intravenous and oral doses , respectively . The corresponding plasma levels ranged from 0.05 to 56 ng/ml and from 0.05 to 104 ng/ml , respectively . In comparison to the parallel US trial , the mean oral doses in this European study were about 20 % lower and the mean blood concentrations were 40 % lower . However , the efficacy in these two trials was similar . No significant relationship between blood levels and selected adverse events or serum creatinine concentrations were observed in the European study ( 6-month data ) . An analysis of plasma protein and albumin concentrations showed an increase to normal ranges 4 - 8 weeks post-transplantation . The level of both markers remained lower in patients who withdrew due to adverse events Hepatitis C virus (HCV)-induced cirrhosis is the commonest indication for orthotopic liver transplantation , but HCV recurrence is nearly universal and may worsen patient / graft outcomes . The frequency and severity of HCV recurrence has apparently increased in recent years , raising concern about a possible role for newer immunosuppression regimens in this increase , including potentially tacrolimus . We r and omized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation . A pathologist blinded to treatment review ed serial liver biopsies . Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus- and cyclosporine-treated patients were .38 and .54 ( P = .19 ) and failure / death were .25 and .28 , respectively ( P = .789 ) . Although cyclosporine-treated patients had significantly larger increases in median serum HCV RNA levels ( months 1 , 6 , and 12 ) , no significant differences were observed between the two treatment arms in histologically-diagnosed HCV recurrence / survival rates . In conclusion , choice of calcineurin inhibitors does not impact severity of recurrent HCV Triple therapy combining an anticalcineurin agent , corticosteroids , and azathioprine ( AZA ) in liver transplantation has been frequently applied , particularly in Europe . Debates have arisen concerning the use of a third drug ( AZA ) , mainly in patients receiving tacrolimus ( TAC ) . An open-label , multicenter , prospect i ve , and r and omized trial was performed to assess the efficacy and safety of TAC and corticosteroids ( dual therapy [ D ] ) vs. TAC , corticosteroids , and AZA ( triple therapy [ T ] ) in liver transplantation . A total of 180 patients were r and omized , 92 in D and 88 in T group . Patients were followed during 3 months for efficacy and safety and up to 24 months for patient and graft survival assessment s. The rate of biopsy-proven acute rejection was higher in D than in T group ( 40.7 % vs. 24.4 % ; P = 0.021 ) . A higher incidence of positive HCV status in D group ( 55.6 % vs. 40.7 % ; P = 0.049 ) may explain this difference , since significantly more patients of this HCV sub population experienced acute rejection when treated with D therapy ( 48 % vs. 20 % ; P = 0.008 ) . No treatment differences were apparent for HCV-negative patients . The 24-month graft survival tended to be inferior in T group , 69.8 % vs. 75.8 % ( P = 0.283 ) . Similar results were observed regarding patient survival at the same time point , with values of 72.9 % vs. 76.9 % ( P = 0.573 ) , favoring D group . Both regimens showed comparable safety profiles with the exception of hematological abnormalities , which were more frequently observed in T group . In conclusion , both regimens were shown to be effective although increased toxicity and a trend towards a lower graft and patient survival were observed in T group BACKGROUND Many reports of successful early withdrawal of regular maintenance steroids in transplant recipients have appeared in recent years . The question now arises whether , in the current age of powerful nonsteroidal immunosuppressants such as Neoral and Tacrolimus , routine administration of steroids posttransplant is necessary at all . This single center pilot study reports on the feasibility , safety , and efficacy of single agent immunosuppression " ab initio " with either Neoral or Tacrolimus , and no routine or maintenance steroids . METHODS A total of 64 adult patients receiving first liver grafts for a variety of indications were r and omized to receive either Neoral 5 mg/kg BDS or Tacrolimus 0.05 mg/kg BDS orally . Liver biopsies were performed on postoperative days 5 and 10 , and whenever else clinical ly indicated . Rejection episodes were treated with 1.0 g of Methylprednisolone daily for 3 consecutive days . A further episode of rejection after two courses of Methylprednisolone was considered to be monotherapy failure , and consequently other immunosuppressive agents , usually Prednisolone 1 mg/kg/day , was started on a regular basis , tapering slowly . RESULTS Actuarial 1 year survival was 85 % for Tacrolimus patients , and 78 % for Neoral patients ( P = NS ) , with 80 % for Tacrolimus and 73.5 % for Neoral at 30 months . Graft survival at 1 and 2.5 years was 73 and 62 % for Tacrolimus and Neoral , respectively ( P = NS ) . Two-thirds of patients in both groups showed biopsy evidence of acute cellular rejection . Rejection severity measured by a histological scoring system was similar for both patient groups . Additional longterm immunosuppressive therapy was necessary in 36 % of patients receiving Neoral , compared with 13 % of Tacrolimus patients ( P = NS ) . No graft was lost on account of acute or chronic rejection . Short-term pulse steroid therapy to treat acute rejection was necessary for 60 % of Tacrolimus patients and 40 % of Neoral patients . CONCLUSION Tacrolimus or Neoral monotherapy after liver transplantation provides adequate immunosuppression for 87 % of Tacrolimus patients and 64 % of Neoral patients . In this study , 33 % of patients in both groups showed no evidence of acute rejection , either clinical ly , biochemically or histologically , and were not exposed to steroids at any time . Evaluation of the long-term morbidity related to the side effects of the immunosuppressants given as monotherapy , for example , renal impairment and posttransplant lymphoproliferative disorder , and the effect on recurrent viral hepatitis in the graft , would be suitable areas for further study Background Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration . Methods In a prospect i ve , multicenter , open-label study , de novo liver transplant patients were r and omized at day 30 to ( i ) everolimus + reduced exposure tacrolimus ( EVR + Reduced TAC ) , ( ii ) everolimus + tacrolimus elimination ( TAC Elimination ) , or ( iii ) st and ard exposure tacrolimus ( TAC Control ) . Results R and omization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection ( tBPAR ) during TAC withdrawal . Of 370 patients who completed the 24-month core study on-treatment , 282 ( 76.2 % ) entered an additional 12-month extension phase . The composite efficacy failure endpoint ( tBPAR , graft loss or death ) occurred in 11.5 % of EVR+Reduced TAC patients versus 14.6 % TAC Controls from r and omization to month 36 ( difference , ‐3.2 % ; 95 % confidence interval , ‐10.5 % to 4.2 % ; P = 0.334 ) . Treated BPAR occurred in 4.8 % versus 9.2 % of patients ( P = 0.076 ) . From r and omization to month 36 , mean ( SD ) estimated glomerular filtration rate decreased by 7.0 ( 31.3 ) mL/min per 1.73 m2 in the EVR+Reduced TAC group , and 15.5 ( 22.7 ) mL/min per 1.73 m2 in the TAC Control group ( P = 0.005 ) . Rates of adverse events , serious adverse events , and discontinuation due to adverse events were similar in both groups during the extension . Conclusions A clinical ly relevant renal benefit after introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study , with comparable efficacy and no late safety concerns BACKGROUND Tacrolimus in combination with prednisolone has been proven to be a safe and effective immunosuppressive induction therapy in solid organ transplantation . However , it remains unclear whether a tacrolimus-based quadruple induction regimen with azathioprine and an antilymphocytic preparation could further improve the results after orthotopic liver transplantation . Therefore , we design ed a prospect i ve , r and omized study to compare the immunosuppressive efficacy of dual ( tacrolimus and prednisolone ) and quadruple ( tacrolimus , azathioprine , ALG Merieux and prednisolone ) induction after liver transplantation . METHODS After r and omization , 120 consecutive patients of primary liver transplants were divided into the dual group ( n=59 ) and the quadruple group ( n=61 ) and followed for a minimum of 3 years . RESULTS Patient survival at 3 years was 88.2 % in the dual versus 94.9 % in the quadruple group . Overall 25 patients in each group ( 41 and 42 % , respectively ) developed acute rejection . There was no difference in the number and severity of rejections . In each group only four patients required OKT3-therapy , however , although three of four patients in the quadruple group responded to OKT3 and cleared rejection , none of the four patients in the dual group were treated successfully with OKT3 ( P<0.02 ) . Rejection in these patients resolved only after additional treatment with mycophenolate mofetil . Adverse events and infections were equally distributed in both groups . Asymptomatic Cytomegalovirus infections were more common in the quadruple group ( P<0.02 ) . As of today , only one patient developed posttransplant lymphoproliferative disease ( dual group ) . CONCLUSIONS The data from our single-center study indicate that both tacrolimus-based dual and quadruple immunosuppressive induction regimens yield similar safety and effectiveness after liver transplantation OBJECTIVES Steroids are a mainstay of treatment in orthotopic liver transplantation ( OLT ) and are associated with significant morbidity . This trial was conducted to assess the efficacy of steroids avoidance . METHODS Patients undergoing OLT between June 2002 and April 2005 were entered into a prospect i ve , r and omized trial of complete steroids avoidance and followed until November 2011 . Recipients received either st and ard therapy ( n = 50 ) or complete steroids avoidance ( n = 50 ) . Analyses were performed on an intention-to-treat basis . The mean follow-up of all recipients was 2095 ± 117 days . Sixteen ( 32 % ) recipients r and omized to the steroids avoidance group ultimately received steroids for clinical indications . RESULTS Incidences of diabetes and hypertension prior to or after OLT were similar in both groups , as was the incidence of rejection . Patient and graft survival rates at 1 , 3 and 5 years were lower in the steroids avoidance group than in the st and ard therapy group ( patient survival : 1-year , 80 % versus 86 % ; 3-year , 68 % versus 76 % ; 5-year , 60 % versus 72 % ; graft survival : 1-year , 76 % versus 76 % ; 3-year , 64 % versus 74 % ; 5-year , 56 % versus 72 % ) , but the differences were not statistically different . CONCLUSIONS Complete steroids avoidance provides liver transplant recipients with minimal benefit and appears to result in a concerning trend towards decreased graft and recipient survival . The present data support the use of at least a short course of steroids after liver transplantation Background Cyclosporine has antiviral activity in vitro against hepatitis C ( HCV ) . We performed a pilot study to prospect ively determine the antiviral effect of cyclosporine during therapy with PEGalfa-2a and ribavirin in liver transplant recipients with recurrent HCV infection . Methods Patients with HCV recurrence ( Ishak Fibrosis Stage ≥ 2 ) were enrolled for 2 years at the University of Florida . Thirty-eight patients were r and omized to continued tacrolimus or switched to cyclosporine . Both groups received PEGalfa-2a and ribavirin . Results Twenty patients received tacrolimus and 18 cyclosporine , with a mean age of 53 . Eighty-two percent were men , 84 % Caucasian , and 90 % genotype 1 . In patients switched from tacrolimus to cyclosporine , HCV-RNA levels decreased by a mean of 0.39 million IU/ml during the 1 month prior to initiating PEG/RBV . Sustained viral response for cyclosporine was higher than in patients on tacrolimus receiving PEG/RBV therapy . Conclusions This r and omized controlled pilot study is the first in vivo study evaluating cyclosporine versus tacrolimus in liver transplant recipients undergoing antiviral therapy . Change from tacrolimus to cyclosporine led to a modest HCV RNA drop and appeared to enhance the antiviral response of PEG/RBV . A larger r and omized study is necessary to see if cyclosporine offers any advantage over tacrolimus Lymphoproliferative disorders ( LPDs ) are a serious side effect of immunosuppression after liver transplantation , and the introduction on the market of a new immunosuppressive drug has been associated with an increased risk of these disorders . To compare the effect of cyclosporine A ( CSA ) and FK506 in a clinical setting , the incidence of monoclonal or oligoclonal gammopathies known to often precede the appearance of LPDs was evaluated . A total of 88 adult patients was analyzed , 46 were prospect ively r and omized to CSA and 42 to FK506 for immunosuppression . None of these patients had gammopathy before transplantation . All the patients were tested for immunoglobulin abnormalities five to nine times during a period of 1 year and then two to four times per year thereafter from December 1990 until March 1997 . The same incidence of serum immunoglobulin ( Ig ) abnormalities was observed in both groups ( 13 % ) with a mean delay of appearance of 11.1 + /- 5.9 versus 7.6 + /- 3.6 months for CSA and FK506 , respectively ( P > .05 ) . In each group , the gammopathies were transient in 3 patients and persisted in 2 . The class of Ig involved was IgG , and a monoclonal component was documented in 2 patients treated with CSA and in 3 patients with FK506 . One patient treated with FK506 developed an LPD localized to the lymph nodes 8 months after the occurrence of serum protein abnormalities . The lymphoproliferative lesions subsequently disappeared with the reduction of immunosuppression . In this study , an immunosuppressive regimen of FK506 has not shown an increased incidence of lymphoproliferation compared with CSA in adult liver transplant patients Long-term renal function was compared in 49 liver recipients [ 25 patients received cyclosporin ( CyA ) and 24 patients received FK 506 ] followed for a period of 1 year . Creatinine ( CR ) and glomerular filtration rate ( GFR ) pretransplantation ( pre-Tx ) and at 1 , 3 , 5 , and 12 months post-Tx were recorded , as well as incidences of hyperkalemia , post-Tx hypertension , and insulin-dependent diabetes mellitus ( IDDM ) in the two groups . At 1 year post-Tx , the mean Cr had risen from baseline by 56 % and 60 % in the FK and CyA groups , respectively ; the mean GFR had dropped by 32 % in FK patients and by 27 % in CyA patients . Acute nephrotoxicity occurred in 7/25 CyA patients ( 2/7 required dialysis ) and 9/26 FK patients ( 7/9 required dialysis ; 2/7 were switched to CyA ) . None remained on dialysis at 3 months . Renal insufficiency persisted at 1 year in 7/16 patients with early toxicity ( CyA , 4 ; FK , 3 ) and in 3 of the remaining 36 pts ( P < 0.001 ) . Hyperkalemia occurred in 4/25 CyA , and in 12/24 FK patients ( P < 0.025 ) , post-Tx hypertension occurred in 15 CyA , and 7 FK patients ( P < 0.05 ) , and IDDM occurred in 4 CyA and 7 FK patients ( P = ns ) . FK 506 and CyA , thus , exerted similar chronic renal effects . Although acute renal insufficiency improved upon dose reduction , renal impairment was permanent in some cases The severity of recurrent hepatitis C virus ( HCV ) is likely related to several factors . Controversial results have been reported regarding the effect of specific calcineurin-inhibitors . The aim of this research was to determine whether there are differences on posttransplantation outcome in HCV-infected patients based on initial immunosuppression . Prospect i ve r and omized trial comparing tacrolimus vs. cyclosporine-based immunosuppression in a cohort of patients undergoing primary orthotopic liver transplantation between 2001 and 2003 was used . Yearly biopsies were performed . Patients with at least 1 protocol biopsy and those with very severe recurrence despite a follow-up of less than 1 yr ( cholestatic hepatitis , progression to bridging fibrosis/cirrhosis ) were included . Baseline characteristics ( demographics , liver function at transplantation , genotype distribution , donor , surgery , immunosuppression except for the type of calcineurin inhibitor ) did not differ between the 2 groups . Severe disease ( defined as bridging fibrosis , cirrhosis , cholestatic hepatitis , and /or death due to recurrent disease in the first year ) was present in 27 in 90 ( 30 % ) , and was equally distributed in the cyclosporine and tacrolimus groups ( 15/46 vs. 12/44 , respectively ) . A total of 33 in 90 ( 37 % ) patients had no fibrosis in the first year biopsy with no difference between the cyclosporine and tacrolimus groups ( 36.5 vs. 37 % ) . The percentage of patients developing recurrent acute hepatitis was also similar ( 32 % vs 35 % ) ; time to acute hepatitis though was shorter in the tacrolimus group ( 59 days [ 35 - 185 ] vs. 92 days [ 39 - 343 ] in the cyclosporin group ; P = 0.02 ) . Cholestatic hepatitis was observed in 4 of 44 and 5 of 46 patients under cyclosporine and tacrolimus , respectively ( P = not significant ) . In conclusions , the short-term posttransplantation course of hepatitis C is not related to the calcineurin inhibitor used Abstract : Background : Interventions that minimize hepatic ischemia/reperfusion injury ( IRI ) can exp and the donor organ pool . Thymoglobulin ( TG ) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients . This controlled r and omized trial was design ated to assess the ability of TG to protect against IRI in liver transplant recipients BACKGROUND Long-term complications of calcineurin inhibitor (CNI)-based immunosuppression after liver transplantation ( LT ) have a marked impact on patient morbidity and mortality . METHODS In this prospect i ve study , LT patients with renal dysfunction were r and omized ( 2:1 ) to either receive mycophenolate mofetil ( MMF ) followed by stepwise reduction of CNI with defined minimal CNI trough levels ( MMF group ) or to continue their maintenance CNI dose ( control group ) . RESULTS In the MMF group ( n = 60 ) , renal function assessed by serum creatinine improved > 10 % in 67 % of patients , was stable in 32 % , and deteriorated > 10 % in 2 % after 12 months compared with baseline values . Mean serum creatinine levels ( + /-SD ) significantly decreased from 1.86 + /- 0.43 to 1.55 + /- 0.38 mg/dL and the corresponding calculated glomerular filtration rate ( cGFR ) significantly increased from 39.9 + /- 10.1 to 49.2 + /- 11.9 mL/min over a 12-month follow-up period . Blood pressure and levels of liver enzymes significantly decreased , and no allograft rejection occurred . In the control group ( n = 30 ) , there were no significant changes in mean serum creatinine and cGFR ( 1.78 + /- 0.59 mg/dL at baseline vs 1.93 + /- 0.86 mg/dL at month 12 , and 41.3 + /- 13.2 mL/min vs 38.7 + /- 11.2 mL/min , respectively ) , liver enzymes and blood pressure throughout the study . CONCLUSIONS Combined MMF and minimal dose CNI therapy after LT is safe , and improves kidney function and the cardiovascular risk profile Corticosteroid therapy contributes significant toxicity to liver transplantation . The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A ( micro-CsA ) . The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation . From the seven Canadian adult liver transplant centers , 143 patients were r and omly allocated oral treatment with either tacrolimus ( n = 71 ) or micro-CsA ( n = 72 ) , together with corticosteroids and azathioprine . Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months , and prednisone < /=0.15 mg/kg/d . In eligible patients , the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved . At 1 year after transplantation , 75 % of the tacrolimus patients and 63 % of the micro-CsA patients were steroid-free ( P = .20 ) . Of all of the patients who became eligible for steroid withdrawal , steroid discontinuation was achieved in over 80 % . One-year patient survival was 97 % with tacrolimus and 89 % with micro-CsA ( P = .052 ) . Graft survival was 97 % and 86 % , respectively ( P = .017 ) . The overall incidence of acute rejection during the first year was 35 % with tacrolimus and 43 % with micro-CsA ( P = .26 ) . There was no difference in survival , acute rejection , or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive . Steroid-resistant rejection occurred in 5.6 % of the tacrolimus and 9.7 % of the micro-CsA patients . One patient , in the micro-CsA group , experienced refractory rejection . Chronic rejection was not observed in either group . The toxicity profiles were similar . Postoperative serum creatinine levels were similar , and dialysis was required in less than 10 % of patients in each group . Infectious complications were similar in both groups . Neurotoxicity was a serious adverse event in 13 % and 10 % of patients receiving tacrolimus and micro-CsA , respectively . Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis AIM study impact of steroid avoidance on HCV recurrence after transplantation . METHODS AND MATERIAL 35 HCV pats , being part of prospect i ve , r and omized , double-blind , placebo-controlled study comparing Tacrolimus (TAC)-Placebo ( PLAC ) ( n = 14 ) to TAC-short-term ( 2 mo ) low-dose steroid ( STER ) ( n = 21 ) , had 5 years follow-up . Primary endpoint was 1 and 5 years survival ; secondary ( composite ) endpoint comprised HCV related cirrhosis , re-transplantation ( re-LT ) and death . RESULTS 1 and 5-years survival were 93 % and 75 % in TAC-PLAC group ; 91 % and 66 % in TAC-STER group ( p 0.38 ) . Two ( 14.3 % ) TAC-PLAC pats died due to HCV cirrhosis at 54 and 72 mo ; 7 ( 33 % ) TAC-STER pats died due to cholestatic hepatitis at 5.8 and 9 mo , to cirrhosis at 18 , 22 , 34 , 73 and 79 mo ( p 0.20 ) . Composite endpoint at 5 years did n't show advantage in favor of TAC-PLAC patients ( 5/14 [ 35.7 % ] vs. 9/21 [ 42.8 % ] pts , p.0.69 ) . Early biopsies seemed more favorable in TAC-PLAC pats ; at 5 years results were identical for both groups . Only 1 ( 7.1 % ) TAC-PLAC and 2 ( 9.5 % ) TAC-STER pats needed rejection treatment . CONCLUSION immunosuppression using steroid avoidance or short-term use had similar outcomes . Well documented long-term follow-up , including biopsies , is necessary in order to make conclusions in relation to impact of steroid use on outcome of HCV liver recipients Recurrence of hepatitis C ( HepC ) has been a most difficult dilemma in liver transplantation ( OLT ) because the effects of immunosuppression with steroid , mycophenolate mofetil ( MMF ) calcineurin antagonists , and anti-interleukin-2 antibody as well as the role of preemptive antiviral therapy are uncertain . In this study , we r and omized OLT recipients with HepC into two treatment arms : tacrolimus+daclizumab+MMF ( study arm ) versus tacrolimus+steroids+MMF ( control arm ) . The study arm only received steroids for the treatment of biopsy-proven rejection episodes . Both arms received preemptive anti-viral therapy with Pegasys and ribavirin . The 39 enrolled patients ( among 50 to be enrolled ) have median follow-up of 458 days with 23 patients ( 8 in study arm , 15 in control arm ) having reached 1 year . The incidences of rejection episodes within 0 to 3 months , 3 to 6 months , and 6 to 12 months were ( study vs control ) : 0 % vs 28 % ; 0 % vs 6 % ; and 13 % vs 20 % ; respectively ( P = NS ) . The 1-year protocol biopsies showed advanced fibrosis ( stage 3 or greater ) in 20 % ( 3 of 15 ) of the control arm , but none ( 0 of 7 ) of the study arm ( P = NS ) . We compared anticipated side effects of steroids in the first 3 months ( study vs control ) : hypertension ( 36 % vs 58 % , P = NS ) , PTDM ( 7 % vs 43 % , P = .02 ) , and wound infections ( 14 % vs 37 % , P = NS ) . In conclusion , liver transplant recipients with HepC tolerate a steroid-free protocol . There was a trend toward reduced steroid side effects and a lower incidence of advanced fibrosis in 1-year biopsy sample s among patients receiving the steroid-free protocol BACKGROUND Choice of calcineurin inhibitor may influence response to antiviral therapy in liver transplant patients with hepatitis C virus ( HCV ) infection . MATERIAL AND METHODS In a r and omized , multicenter , 80-week trial , liver transplant recipients ( > 6 months and £ 10 years post-transplant ) with recurrent HCV infection received cyclosporine ( n=50 ) or tacrolimus ( n=42 ) with a 48-week course of pegylated interferon ( peg-IFNα2a ) and ribavirin . Twenty-three patients in each group completed the trial on study medication . The primary endpoint was sustained virological response ( SVR ) 24 weeks after the end of antiviral therapy , for which 43 patients were eligible for analysis . RESULTS The rate of SVR was 60.0 % ( 12/20 ) with cyclosporine and 43.5 % ( 10/23 ) with tacrolimus ( adjusted odds ratio 1.85 ; 95 % CI 0.53 - 6.43 ; p=0.331 ) . There were no significant intergroup differences for rapid or early virological response , relapse , HCV RNA viral load , or fibrosis progression . One cyclosporine-treated patient experienced acute rejection . One patient died in each group . Adverse events , treatment-related adverse events , and serious adverse events were similar between groups . CONCLUSIONS Since fewer patients were recruited than planned ( 92 versus 355 ) , the study was underpowered and robust conclusions can not be drawn regarding the effect of cyclosporine and tacrolimus on virological responses to antiviral treatment for recurrent HCV after liver transplantation . However , as reported in other trials , SVR was higher in cyclosporine-treated patients Background . Basiliximab ( B ) , an anti-CD25 monoclonal antibody , may represent an alternative to steroids ( S ) in immunosuppression after liver transplantation ( LTx ) . The aim of this prospect i ve r and omized clinical trial was to compare B with S in a cyclosporin A (CsA)-based immunosuppression regimen in primary LTx . Methods . Forty-seven adult recipients of LTx were r and omly assigned to receive B or S. CsA was administered at the initial dose of 10 mg/kg/day and adjusted to the target C2 level of 800 to 1000 ng/mL by day 7 . Clinical ly suspected acute cellular rejection ( ACR ) was histologically confirmed . Endpoints include ACR , survival , and disease-free survival . Results . In group B ( 26 patients ) , there were seven biopsy-confirmed ACR with an ACR rate of 15.4 % ; in group S ( 21 patients ) , 8 ACR with an ACR rate of 28.6 % ( P = n.s . ) . Cumulative survival at 36 months after transplantation was 84.3 % for group B and 61.0 % for group S. In hepatitis C virus patients ( n=20 : 12 in group B , 8 in group S ) , the ACR rate was 25 % in group B and 50 % in group S. The incidence of infection and other adverse events was similar in the two treatment groups . Conclusions . B may represent a valid alternative to S in the induction of immunosuppression in LTx . Further studies of basiliximab in a large cohort are needed Biliary lipids output is reduced after liver transplantation and tends to normalize thereafter . Cyclosporine A ( CyA ) is reported to interfere with the normal bile-restoring process after liver grafting , but data are inconclusive , in particular regarding the comparison with the other widely used calcineurin inhibitor tacrolimus ( TCR ) . Furthermore , previous research es were conducted in patients taking multiple immunosuppressive therapies and with a short follow up . In this study we readdressed this issue by comparing biliary lipids in the first 3 months after liver transplant , in 20 patients r and omized to receive immunosuppression with CyA or TCR monotherapy . Bile sample s , harvested through a T-tube at days 1 , 3 , 7 , 15 , 30 , 60 and 90 were assessed for cholesterol , phospholipids , and total and individual concentrations of bile acids ( BA ) . Liver and kidney function tests were evaluated as well . We found no differences between CyA and TCR in biochemical findings or in total biliary BAs , cholesterol , and phospholipids . However , CyA-treated patients showed lower levels of glycochenodeoxycholic acid at day 15 , compared to those treated with TCR ( P < 0.04 ) . This difference normalized thereafter , without any biochemical or clinical effect at 3-month follow up Neurotoxicity is a serious complication following orthotopic liver transplantation leading to increased morbidity and mortality . Neurotoxicity may be evoked by various perioperative factors , or may be due to drug-specific toxicity of immunosuppression . In the present study we evaluated the incidence of central nervous system ( CNS ) toxicity occurring within the early postoperative period of 121 patients , 61 r and omly assigned to FK 506- and 60 to CsA-based immunosuppression as part of a multicentre study . The incidence of moderate or severe CNS toxicity was higher in patients treated with FK 506 ( 21.3 % ) than in patients receiving CsA ( 11.7 % ) . The duration of symptoms was also greater in patients treated with FK 506 than in patients receiving CsA. The incidence of moderate or severe neurotoxicity after retransplantation was markedly greater in patients treated with FK 506 ( 100 % of the patients ) Background . Due to the known high recurrence rate of hepatitis C virus ( HCV ) among orthotopic liver transplant ( OLT ) recipients who receive tacrolimus+corticosteroid maintenance , use of steroid-free induction was considered . Methods . OLT recipients with HCV were r and omized to receive tacrolimus+daclizumab ( steroid-free ) vs. tacrolimus+corticosteroids during 1999–2001 and then tacrolimus+mycophenolate mofetil (MMF)+daclizumab ( steroid-free ) vs. tacrolimus+MMF+corticosteroids during 2002–2005 . Patients in the steroid-free arm of both periods received no steroids except for treating biopsy-proven rejection . Primary objective was to compare mean fibrosis stage at the 1-year protocol biopsy , between the steroid-free and corticosteroid arms , stratifying by period . Results . No noticeable differences in mean fibrosis stage between the two treatment arms , either averaging across periods ( P=0.99 ) or during either period ( P>0.35 ) were found . Occurrence of acute rejection during the first year was the only factor associated with a significantly increased fibrosis stage at 1 year ( P=0.0003 ) ; stage ≥2 was seen in 63 % ( 17 of 27 ) vs. 19 % ( 8 of 43 ) of those with vs. without rejection . In addition , MMF use was associated with significantly fewer patients experiencing acute rejection during the first 6 and 12 months posttransplant ( P=0.006 and 0.046 ) . Regarding steroid-related side effects , posttransplant diabetes mellitus occurred in 10 % vs. 45 % , and wound infection in 6 % vs. 31 % of steroid-free vs. corticosteroid patients ( P=0.003 and 0.01 ) . Conclusions . OLT recipients with HCV tolerated the steroid-free protocol with fewer side effects ; however , its use had no apparent impact on hepatic fibrosis progression . Occurrence of acute rejection was strongly associated with increased hepatic fibrosis at 1 year , and MMF use appears to have significantly reduced the rejection rate We investigated possible explanations for the common occurrence of perivenular lesions in liver allografts of patients on FK506 within a few weeks to several months after OLT . Hematoxylin and eosin-stained sections of pre- and postperfusion biopsy specimens and day 7 post-transplant protocol biopsy specimens from 31 patients , r and omly assigned to either FK506 or CsA as primary immunosuppressive agent , were review ed , and immu-nohistochemical stains for HLA-DR antigen and S-100 protein were performed by the avidin-biotin peroxidase complex method . The histologic features of cellular rejection in the portal tracts of day 7 posttransplant allograft biopsy specimens from patients on FK506 were milder than those from patients on CsA. Immunohisto-chemical stains for HLA-DR showed intense positivity in a variety of cell types in day 7 posttransplant specimens from both groups , including sinusoidal-lining cells , bile duct epithelial cells , vascular endothelial cells , inflammatory cells , and occasional injured hepatocytes . Although diffuse tabular staining was seen in the majority of cases in both groups , either with or without rejection , liver biopsy specimens from patients on FK506 showed concentration of positively stained cells in perivenular regions more often , and at a lower overall histologic grade of rejection , than specimens from patients on CsA. There were no differences in the number and distribution of S-100 protein-positive dendritic APC between biopsy specimens from FK506 versus CsA-treated patients , or between specimens with and without cellular rejection in either group . It is suggested that the development of perivenular injury , which is seen frequently in allograft biopsy specimens from patients on FK506 obtained at various intervals after transplantation , may be related to drug toxicity rather than to the process of allograft rejection BACKGROUND In OLT induction therapy with interleukin-2-receptor antibodies is often applied as part of the st and ard immunosuppression protocol . It was the aim of this study to determine if Basilixirnab mduction therapy serves to reduce the incidence of acute rejection episodes and improves graft function and survival in the long term after OLT . MATERIAL / METHODS We prospect ively analysed 99 patients transplanted at our institution ( 1997 - 2000 ) . Patients were r and omised to two study groups : 51 patients received Basiliximab induction combined with Calcineurin inhibitors and steroids , 48 patients received CNIs and steroids only . Incidence and severity of rejection , graft and patient survival and intensity of long-term immunosuppression were analysed . Frequency of CNI and steroid induced adverse effects were recorded . RESULTS In our patient collective we could not detect a significant impact of Basiliximab induction therapy on the fre queny of acute or chronic rejection . CNI levels were almost identical in both groups ; graft and patient survival rates were not influenced by the application of induction therapy . CONCLUSIONS In our patient collective induction therapy does not have a general positive influence on the post transplant course . A slight improvement in long term renal function could be detected for Basiliximab treated patients We examined the occurrence of renal complications and hypertension in 540 primary liver recipients entered into the European liver trial comparing primary FK 506 to a cyclosporin A based immunosuppression regimen ( CBIR ) . No difference in serious renal impairment or mean creatinine levels was observed with similar rates of " kidney failure " ( FK 506 9.4 % vs. CBIR 7.3 % ) and dialysis requirements ( FK 506 12 % vs. CBIR 11 % ) . " Abnormal kidney function " , a less serious parameter of renal impairment , was reported in 89 recipients ( 33 % ) in the FK 506 group versus 58 ( 21 % ) in the CBIR group ( P < 0.01 ) . Development of this complication was associated with elevated intravenous FK 506 dosing schedules , with the mean cumulative dose 43 % higher than treated patients with unaffected kidney function . In a later cohort of patients where intravenous dosing was lower , no significant difference in renal complications was detectable . The 6-month prevalence rate of systemic arterial hypertension was noted to be lower in the FK 506-treated patients compared to the CBIR group [ 33 ( 17.2 % ) vs. 47 ( 25.7 % ) ] The aim of this study was to evaluate the impact of a steroid‐free regimen with tacrolimus and mycophenolate mofetil ( modified therapy ) vs. a st and ard regimen of tacrolimus and steroids on the cardiovascular risk score of liver transplant recipients . Patients who received a liver transplant were r and omized to a modified therapy ( n = 58 ) or a st and ard regimen ( n = 59 ) . Both groups were balanced at baseline , except for a higher prevalence of diabetes mellitus ( DM ) ( p < 0.01 ) and a higher serum creatinine concentration ( p < 0.05 ) in the modified therapy group . After 12 months , the prevalence of new‐onset DM , arterial hypertension , hypercholesterolemia , hypertriglyceridemia , and changes in cardiovascular risk factors was similar in both groups . The increase in serum creatinine ( mg/dL ) compared to baseline at one yr post‐transplantation was numerically lower in the modified therapy group ( 0.22 ± 0.42 ) than in the st and ard regimen group ( 0.41 ± 0.67 ) ( p = 0.068 ) . Although estimated cardiovascular risk score did not vary significantly compared to baseline in either group , there was a slight reduction in the modified regimen ( −0.27 ± 2.87 ) vs. a mild increase ( 0.17 ± 2.94 ) in the st and ard regimen ( p = 0.566 ) . In conclusion , a steroid‐free regimen with tacrolimus and mycophenolate mofetil was associated with a trend toward better preservation of kidney function and reduction of cardiovascular risk score We evaluate 5-year results of a prospect i ve r and omized trial that compared cyclosporine microemulsion ( CsA-me ) and Tacrolimus ( Tac ) for primary immunosuppression . One hundred one adult patients undergoing liver transplantation were r and omized to receive Tac ( n = 50 ) or CsA-me ( n = 51 ) . The most frequent indication for the procedure was cirrhosis due to virus C followed by alcoholism . Survival rates at 1 , 3 , and 5 years were 86 % , 75 % , and 72 % , respectively ; there was no significant difference between CsA-me versus Tac arms . Acute rejection occurred in 30 cases ( 30 % ) , independent of the type of primary immunosuppression . Serious adverse events were reported significantly more among patients under CsA-me ( 48 episodes ) than under Tac ( 32 episodes ) . Nineteen patients were switched to the other calcineurin inhibitor . The switch was much more frequent from CsA-me to Tac ( n = 15 ; 29.4 % ) , mainly because of lack of efficacy ( n = 10 ; 19.6 % ) . There were no cases of chronic rejections in the Tac arm . Four patients were switched from Tac to CsA-me for side effects ; only 1 remains alive , after treatment was changed from CsA-me to an antimetabolite . There were no statistical differences in renal dysfunction , diabetes , hypertension , neurologic disorders , new-onset malignancies , or infections . There were no differences in survival or rejection among the intention-to-treat groups . Serious adverse events , total patients with switch of calcineurin inhibitor , as well as switches due to lack of efficacy , were statistically more frequent under CsA-me . Tacrolimus seems to be a more appropriate drug to be used for primary immunosuppression in liver transplantation BACKGROUND / AIMS We describe the histological patterns of rejection in liver transplant recipients using induction therapies with cyclosporine and tacrolimus monotherapy compared with st and ard triple therapy as historical control . METHODS Patients formed part of the initial cohort in an open-labelled , r and omised pilot study and were selected consecutively if they had histological rejection and no other confounding diagnoses . There were 13 patients in the cyclosporine monotherapy group ( CsA ) , 11 in the tacrolimus monotherapy group and 13 in the triple therapy group ( CAP ) . The histology of liver biopsies was reassessed blindly and the severity of rejection was recorded . RESULTS The total Royal Free Hospital ( RFH ) rejection scores as well as other histological features ( zone 3 haemorrhage , apoptosis in zones 1 and 3 , steatosis , cholestasis , nuclear vacuolation , lymphoblasts and ballooning ) were comparable in the three groups . There was no difference in individual components of the histological features comprising the diagnosis of rejection , except that the portal inflammation score was significantly lower in the tacrolimus group when compared with the CsA group ( p=0.04 ) . There was no significant difference in the number of patients with moderate/severe rejection between the three groups . Overall , there was no significant increase in histological severity of rejection in the monotherapy groups . CONCLUSIONS The results suggest that the monotherapy may be as effective as the triple therapy in the initial post-transplant phase and that no particular graft histological changes were associated with the type of treatment Liver transplantation has never been the subject of a r and omized controlled trial , and there remains uncertainty about the magnitude of benefit and cost-effectiveness for specific patient groups . This article reports the results of an economic evaluation of adult liver transplantation in Engl and and Wales . Patients placed on the waiting list for a liver transplant were observed over 27 months . The costs and health benefits of a comparison group , representing experience in the absence of liver transplantation , were estimated using a combination of observed data from patients waiting for a transplant and published prognostic models . The analysis focuses on three disease groups , for each of which prognostic models were available : primary biliary cirrhosis ( PBC ) , alcoholic liver disease ( ALD ) , and primary sclerosing cholangitis ( PSC ) . A higher proportion of patients with ALD were assessed for a transplant but not placed on the waiting list . The estimated gain in quality -adjusted life-years from transplantation was positive for each of the disease groups . The mean incremental cost per quality -adjusted life-year ( 95 % bootstrap confidence intervals ) from time of listing to 27 months for patients with PBC , ALD , and PSC are pound 29,000 ( pounds 1,000 to pounds 59,000 ) , pounds 48,000 ( pounds 12,000 to pounds 83,000 ) and pounds 21,000 ( -pounds 23,000 to pounds 60,000 ) , respectively . In conclusion , liver transplantation increases the survival and health-related quality of life of patients with each of three end-stage liver diseases . However , the extent of this increase differs between different disease groups . Cost-effectiveness estimates were poorer for patients with ALD over the 27-month period than for patients with PBC or PSC . This in part reflects the costs of the higher number of ALD patients assessed for each transplant Eighty-one liver recipients were r and omised to FK 506 or cyclosporin ( CyA ) and azathioprine ( AzA ) , both in combination with steroids . Twenty-seven FK 506 and 29 CyA/AzA patients continued in the trial 3 months after transplantation . Steroids were ceased in 23 ( 85 % ) FK 506 patients and in 27 ( 93 % ) CyA patients . After steroid withdrawal , 2 FK 506 and 4 CyA patients were excluded from the study , all for reasons other than rejection . The median follow-up was 16 months for the FK 506 , and 19 months for CyA group . There were no acute rejection episodes or graft losses in the FK 506 group . None of the CyA patients lost their graft but three ( 13 % ) had episodes of acute rejection requiring steroids to be recommenced in two cases . There was no evidence of chronic rejection in any of the annual review biopsies in either group . Our results suggested no advantage of FK 506 over CyA in its steroid-sparing effect Posttransplant chronic renal failure , secondary to calcineurin inhibitor agents , is emerging as a major problem in liver transplantation . We report a r and omized clinical trial comparing daclizumab , delayed low-dose tacrolimus ( target trough level 4 - 8 ng/mL , starting day 4 - 6 ) , Investigational Arm ( n = 72 ) , to st and ard tacrolimus induction/maintenance dosing , St and ard Arm ( n = 76 ) , with mycophenolate mofetil and tapering corticosteroids in both study arms . The end-points were renal function indicated by the Modification of Diet in Renal Disease ( MDRD ) . There was no significant difference in patient survival ( 86.6 % Investigational Arm vs. 92.9 % St and ard Arm ; P = 0.21 ) or acute rejection ( 23.2 % vs. 27.7 % , respectively ; P = 0.68 ) . Statistically significant differences in median glomerular filtration rate ( GFR ) were found in favor of the Investigational Arm . With the CG equation , the GFR at the end of the first week was 110.7 vs. 89.6 mL/min ( P = 0.019 ) without significant differences thereafter . With the MDRD , statistically significant differences extended to the first posttransplant month ( 86.8 vs. 70.1 mL/min/1.73 m(2 ) ; P < 0.001 ) with and was seen at month 6 ( 75.4 vs. 69.5 mL/min/1.73 m(2 ) ; P = 0.038 ) . In conclusion , delayed low-dose tacrolimus , in combination with daclizumab and mycophenolate mofetil , preserves early renal function post-liver transplantation without the cost of increased acute rejection Treatment with monoclonal IL-2 receptor antibodies has been successfully used for immunosuppressive induction therapy following organ transplantation in the recent past . The present study was conducted to compare for the first time a cyclosporine-based quadruple immunosuppressive regimen including a monoclonal IL-2 receptor antibody or ATG as induction therapy after orthotopic liver transplantation . In two groups of 33 patients each , postoperative survival , graft biopsies , liver function enzymes , and the clinical courses after OLT were evaluated . Our results indicate that monoclonal IL-2 receptor antibody therapy as part of a quadruple immunosuppressive regimen is better tolerated and is at least as effective as ATG in prevention of allograft rejection following OLT . Furthermore , our data indicate that a slightly better liver function in general and a lower incidence of rejection reactions necessitating treatment could be observed in the group of patients treated with the monoclonal IL-2 receptor antibody . This study provides evidence that monoclonal IL-2 receptor antibody therapy may be a useful tool for the immunosuppressive induction therapy following clinical orthotopic liver transplantation Mycophenolate mofetil ( MMF ) and sirolimus ( SRL ) have been used for calcineurin inhibitor ( CNI ) minimization to reduce nephrotoxicity following liver transplantation . In this prospect i ve , open-label , multicenter study , patients undergoing transplantation from July 2005 to June 2007 who were maintained on MMF/CNI were r and omized 4 to 12 weeks after transplantation to receive MMF/SRL ( n = 148 ) or continue MMF/CNI ( n = 145 ) and included in the intent-to-treat population . The primary efficacy endpoints were the mean percentage change in the calculated glomerular filtration rate ( GFR ) and a composite of biopsy-proven acute rejection ( BPAR ) , graft lost , death , and lost to follow-up 12 months after transplantation . Patients were followed for a median of 519 days after r and omization . MMF/SRL was associated with a significantly greater renal function improvement from baseline with a mean percentage change in GFR of 19.7 ± 40.6 ( versus 1.2 ± 39.9 for MMF/CNI , P = 0.0012 ) . The composite endpoint demonstrated the noninferiority of MMF/SRL versus MMF/CNI ( 16.4 % versus 15.4 % , 90 % confidence interval = -7.1 % to 9.0 % ) . The incidence of BPAR was significantly greater with MMF/SRL ( 12.2 % ) versus MMF/CNI ( 4.1 % , P = 0.02 ) . Graft loss ( including death ) occurred in 3.4 % of the MMF/SRL-treated patients and in 8.3 % of the MMF/CNI-treated patients ( P = 0.04 ) . Malignancy-related deaths were less frequent with MMF/SRL . Adverse events caused withdrawal for 34.2 % of the MMF/SRL-treated patients and for 24.1 % of the MMF/CNI-treated patients ( P = 0.06 ) . The use of MMF/SRL is an option for liver transplant recipients who can benefit from improved renal function but is associated with an increased risk of rejection ( but not graft loss ) The immunosuppressive agent cyclosporin A ( CsA ) is reportedly associated with clinical ly adverse effects on circulating lipid and apolipoprotein concentrations . To date few data have been reported concerning the effects on lipid metabolism of the new macrolide immunosuppressive agent FK 506 , and no comparative studies of the effects of these drugs have been performed . In consideration of the pivotal role of the liver in lipid metabolism , we measured fasting serum lipids and apolipoproteins a median of 8 ( range 5 to 9 ) months after the operation in 20 clinical ly stable liver transplant recipients r and omly allocated to maintenance immunosuppression with CsA + /- azathioprine ( n = 10 ) or FK 506 ( n = 10 ) . To avoid the confounding effects of corticosteroids on lipid metabolism , prednisolone was withdrawn at least 6 weeks beforeh and in each case . Ten healthy volunteers matched for age and body mass index served as control subjects . Serum total cholesterol concentration was significantly lower in both the CsA ( p < 0.001 ) and FK 506 ( p < 0.05 ) treatment groups when compared with the healthy control subjects . Serum high-density lipoprotein ( HDL ) cholesterol concentration was also significantly lower in both the CsA ( p < 0.005 ) and FK 506 ( p < 0.01 ) treatment groups . Neither the ratio of serum total cholesterol to HDL cholesterol nor the fasting triglyceride concentrations were significantly different ( p > 0.1 ) from those of the healthy control subjects for either transplant group . Serum apolipoprotein B level was lower than that of the control group in both the CsA ( p < 0.005 ) and FK 506 groups ( p = 0.06 ) . ( ABSTRACT TRUNCATED AT 250 WORDS 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 Objective : To evaluate patient survival and allograft function and health-related quality of life ( HRQOL ) 20 years after orthotopic liver transplantation ( LT ) . Summary of Background Data : Although LT is the established treatment of choice for acute and chronic liver failure , allograft function and recipient HRQOL 20 years after LT remain undefined . Methods : We performed a prospect i ve , cross-sectional study of LT recipients surviving 20 years or more . Clinical data were review ed to identify factors associated with 20-year survival . Survivors were directly contacted and offered a survey to assess HRQOL ( SF-36 ; Liver Disease Quality of Life ) , social support , and cognition ( Neuropsychological Impairment Scale ) . Logistic regression analysis was performed to identify clinical factors influencing HRQOL 20 years after LT . Results : Between February 1 , 1984 and December 31 , 1988 , a total of 293 patients ( 179 adults , 114 children ) received 348 LTs . Of the 293 patients , 168 ( 56 % ) survived for 20 years or more . Actuarial 20-year survival was 52 % ( patient ) and 42 % ( graft ) . Factors associated with 20-year survival included recipient age < 18 ( P = 0.01 ) , nonurgent LT ( P = 0.01 ) , no retransplantation ( 0.02 ) , female gender ( 0.03 ) , absence of biliary complications ( P = 0.04 ) , and short total ischemia time ( P = 0.05 ) . Rejection episodes were seen in a greater proportion of 20-year survivors than in nonsurvivors ( 35 % vs. 27 % ; P = 0.3 ) . Of the 168 survivors , 87 were contacted , and 68 ( 78 % ) completed the HRQOL surveys . Compared with the general population , survivors had lower physical scores ( P < 0.01 ) but comparable mental scores on the SF-36 . Overall HRQOL was significantly better in 20-year survivors than in patients with chronic liver disease , congestive heart failure , or diabetes . Clinical factors associated with improved post-LT HRQOL were younger age at LT , allograft longevity , and strong social support . More than 90 % of pediatric survivors completed high school . After LT , 34 % of pediatric recipients married , and 79 % remained married at 20 years ' follow-up . Conclusions : More than 50 % of LT recipients survive 20 years , achieve important socioeconomic milestones , and report quality of life superior to patients with liver disease or other chronic conditions . LT is a durable surgery that restores both long-term physiologic and psychologic well-being in patients with end-stage liver disease A large prospect i ve , open‐label , r and omized trial evaluated conversion from calcineurin inhibitor (CNI)‐ to sirolimus (SRL)‐based immunosuppression for preservation of renal function in liver transplantation patients . Eligible patients received liver allografts 6–144 months previously and maintenance immunosuppression with CNI ( cyclosporine or tacrolimus ) since early posttransplantation . In total , 607 patients were r and omized ( 2:1 ) to abrupt conversion ( < 24 h ) from CNI to SRL ( n = 393 ) or CNI continuation for up to 6 years ( n = 214 ) . Between‐group changes in baseline‐adjusted mean Cockcroft – Gault GFR at month 12 ( primary efficacy end point ) were not significant . The primary safety end point , noninferiority of cumulative rate of graft loss or death at 12 months , was not met ( 6.6 % vs. 5.6 % in the SRL and CNI groups , respectively ) . Rates of death at 12 months were not significantly different , and no true graft losses ( e.g. liver transplantation ) were observed during the 12‐month period . At 52 weeks , SRL conversion was associated with higher rates of biopsy‐confirmed acute rejection ( p = 0.02 ) and discontinuations ( p < 0.001 ) , primarily for adverse events . Adverse events were consistent with known safety profiles . In conclusion , liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI‐ to SRL‐based immunosuppression Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression , it is important to establish the superior immunosuppressive agent for the individual patient . In the present study , 121 patients , 61 r and omly assigned to FK506- and 60 assigned to CsA-based immunosuppression , were analyzed according to the primary diagnosis for liver transplantation . One-year patient survival was similar in all groups . However , the incidence and severity of acute rejection within the 1st year after transplantation was significantly higher in patients transplanted due to HCV disease who were receiving FK506 ( 58.8 % ) compared with those patients receiving CsA ( 27.8 % ; p < or = 0.05 ) . Furthermore , the incidence of moderate and severe neurotoxicity was significantly higher during the 1st month after LTX in patients transplanted owing to HCV disease treated with FK506 ( 35.3 % ) compared with those patients receiving CsA ( 16.7 % ; p < or = 0.05 ) . Irrespective of the immunosuppressive regimen , the incidence of early postoperative neurotoxicity was significantly lower in patients transplanted owing to HBV disease , alcoholic cirrhosis and various other liver diseases summarized than in patients transplanted due to HCV disease receiving FK506 therapy . During the 1st year , the incidence and severity of rejection in patients transplanted due to alcoholic cirrhosis and PBC was significantly lower in patients treated with FK506 ( 11.1 % for both groups ) compared with those patients receiving CsA ( 54.5 % and 60.0 % , respectively ; p < or = 0.05 . Furthermore , this was accompanied by a lower incidence of toxicity . ( ABSTRACT TRUNCATED AT 250 WORDS We design ed a r and omized trial to assess whether the early withdrawal of cyclosporine ( CsA ) followed by the initiation of everolimus ( Evr ) monotherapy in de novo liver transplantation ( LT ) patients would result in superior renal function compared to a CsA‐based immunosuppression protocol . All patients were treated with CsA for the first 10 days and then r and omized to receive Evr in combination with CsA up to day 30 , then either continued on Evr monotherapy ( Evr group ) or maintained on CsA with/without mycophenolate mofetil ( CsA group ) in case of chronic kidney disease ( CKD ) . Seventy‐eight patients were r and omized ( Evr n = 52 ; CsA n = 26 ) . The 1‐year freedom from efficacy failure in Evr group was 75 % versus 69.2 % in CsA group , p = 0.36 . There was no statistically significant difference in patient survival between the two groups . Mean modification of diet in renal disease ( MDRD ) was significantly better in the Evr group at 12 months ( 87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min ; p < 0.001 ) . The incidence of CKD stage ≥3 ( estimated glomerular filtration rate < 60 mL/min ) was higher in the CsA group at 1 year ( 52.2 % vs. 15.4 % , p = 0.005 ) . The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novo LT patients is associated with an improvement in renal function , with a similar incidence of rejection and major complications Background Calcineurin inhibitor (CNI)‐related nephrotoxicity significantly contributes to chronic renal failure after liver transplantation Nephrotoxicity represents a serious side effect of immunosuppression following liver transplantation . In order to compare the nephrotoxic action of CsA and FK506 in a clinical setting , we evaluated the incidence of early and late nephrotoxicity in 121 patients , 60 of whom were r and omly assigned to CsA- and 61 to FK506-based immunosuppression . Early postoperative renal insufficiency ( between PODs 0 and 30 ; SCr 1.5 - 3 mg/dl ) was observed to a similar extent in patients treated with CsA ( 38.3 % ) and FK506 ( 42.6 % ) . Early postoperative acute renal failure ( ARF ) ( SCr > 3 mg/dl ) was observed in 18.0 % of patients in the FK506 treatment group and 18.3 % of patients receiving CsA therapy . Approximately half the patients with ARF required hemodialysis ( CsA : 11.7 % ; and FK506 : 8.2 % ) . All patients with early postoperative ARF requiring hemodialysis survived for more than one year . New onset of late ARF ( between PODs 30 and 365 ) was observed in 6.6 % of patients receiving FK506 therapy and in 1.7 % in the CsA treatment group as a result of severe infection with multiple organ failure syndrome ( MOFS ) . There was 100 % mortality in patients with late ARF requiring hemodialysis . Etiology and prognosis of early and late ARF seem to be completely different . Early ARF was associated with severe coagulopathy and a rise in bilirubin and free hemoglobin , and was accompanied by impaired liver function . Mean onset of hemodialysis in CsA-treated patients was POD 1 and in FK506-treated patients POD 6 , which disclosed a different time course of drug-specific nephrotoxicity of CsA and FK506 in early ARF . In contrast , late ARF occurred in both treatment groups only as a part of the MOFS in association with severe infections , an observation consistent with the assumption of overimmunosuppression rather than a primary nephrotoxic effect . Late renal insufficiency appeared in 23.3 % of CsA- and in 29.4 % of FK506-treated patients , and represented a slowly progressing form of drug-specific nephrotoxicity of CsA and FK506 . These preliminary results demonstrate a similar outcome in terms of both early and late nephrotoxicity , but longer follow-up will delineate the overall efficacy and toxicity in humans Objective : To investigate the safety of minimal immunosuppression ( IS ) in liver transplantation ( LT ) . Background : The lack of long-term follow-up studies , including pathologic data , has led to a protean h and ling of IS in LT . Methods : Between February 2000 and September 2004 , 156 adults were enrolled in a prospect i ve , r and omized , double-blind , placebo-controlled minimization trial comparing tacrolimus placebo ( TAC-PLAC ) and TAC short-term steroid ( TAC-STER ) IS . All patients had a minimum clinical , biochemical , and histological follow-up of 5 years . Results : Five-year actual patient and graft survival rates in TAC-PLAC and TAC-STER groups were 78.1 % and 82.1 % ( P = 0.89 ) and 74.2 % and 76.9 % ( P = 0.90 ) , respectively . Five-year biopsies were available in 112 ( 89.6 % ) of 125 survivors . Twelve patients refused a biopsy because of their excellent evolution ; tissue material was insufficient in 1 patient ; 11 had normal liver tests ; and 2 patients had developed alcoholic and secondary biliary cirrhosis . Histology was normal in 44 ( 39.3 % ) patients ; 35 ( 31.3 % ) had disease recurrence . The remaining biopsies showed nonspecific chronic hepatitis ( 14.3 % ) , mild inflammatory infiltrates ( 10.7 % ) , and steatosis ( 3.5 % ) . All findings were equally distributed between both groups . In each group , 3 patients ( 4.8 % ) presented with acute cellular rejection after the first year and only 1 ( 0.9 % ) TAC-PLAC patient developed chronic rejection after IS withdrawal because of pneumonitis . Arterial hypertension , diabetes mellitus , renal insufficiency , hypercholesterolemia , gout , and obesity were equally low in both groups . Conclusions : Excellent long-term results can be obtained under minimal IS and absence of steroids . TAC-based monotherapy is feasible in most adult liver recipients until 5 years of follow-up Background . The aim of this prospect i ve , r and omized , double-blinded , placebo-controlled single center study was to evaluate an early steroid-free immunosuppression in liver transplant patients . Methods . From March 2000 to October 2004 , 110 patients were included . All patients received tacrolimus and steroids during the first 2 weeks after orthotopic liver transplantation ( OLT ) . Thereafter , patients in the steroid group ( n=54 ) received steroids and the remaining 56 a placebo . After 6 months , the immunosuppression for all was steroid free . Thirty patients were hepatitis C positive . Five years after inclusion , patient survival , organ survival , steroid side effects , and recirrhosis in hepatitis C virus ( HCV ) patients were reevaluated . Results . After 5 years , the following parameters were comparable in both groups : patient survival ( P=0.236 ) , organ survival ( P=0.509 ) , and acute rejections ( P=0.409 ) . Steroid-free immunosuppression lead to a higher rate of chronic rejections ( P=0.023 ) . Six months after OLT , there was a difference in rates of posttransplant diabetes mellitus ( PTDM ) ( P=0.024 ) and hypercholesterolemia ( P=0.002 ) . However , 5 years after OLT , there was no difference in hypertension ( P=0.647 ) , PTDM ( P=0.453 ) , hypercholesterolemia ( P=0.412 ) , and osteoporosis ( P=0.624 ) . In HCV patients , we could not find any differences in patient survival ( P=0.096 ) , organ survival ( P=0.424 ) , time free from recirrhosis ( P=0.647 ) . The rate of recirrhosis was influenced by steroid bolus therapy ( P=0.01 ) but not by avoiding continuous steroid therapy . Conclusions . Early tapering down of steroids to a tacrolimus monotherapy is possible with comparable acute rejection rates . During steroid therapy , PTDM and hypercholesterolemia are cumulative . These side effects are reversible . The recirrhosis in HCV patients is not influenced by continuous steroid therapy but more frequent in HCV patients receiving a steroid bolus therapy A prospect i ve r and omised study was conducted to evaluate the efficacy and safety of FK 506 administered with corticosteroids compared with a cyclosporin A-based immunosuppressive regimen in patients undergoing primary liver transplantation . 545 patients were recruited in eight European centres , of whom 267 were r and omised to FK 506 therapy and 273 to cyclosporin A-based therapy . The estimated Kaplan-Meier patient and graft survival figures of 82.9 % and 77.5 % respectively in the FK 506 group were higher than the comparable figures in the cyclosporin A group ( 77.5 % and 72.6 % , respectively ) . These differences did not reach statistical significance . Retransplantation rates , time to first rejection episode and number of rejection episodes were all lower ( P < 0.001 ) in the FK 506 group . The infection rates were comparable between the two groups . During the study , the dose of FK 506 was reduced ; this did not compromise efficacy and reduced the associated toxicity . FK 506 provides effective immunosuppression in patients undergoing primary liver transplantation and is associated with a lower incidence of rejection The introduction of quadruple induction therapy after liver transplantation with the murine anti-interleukin-2 receptor ( IL-2R ) antibody ( BT563 ) has decreased the incidence of serious side effects , such as tachycardia , hypertension , rash , fever and nausea since it does not lyse its target cell . To investigate the immunosuppressive efficacy of BT563 , a placebo-controlled trial was performed and BT563 was added to the st and ard triple induction after liver transplantation . Forty consecutive recipients of primary orthotopic liver transplants ( OLT ) ( median age 47 yr [ range 18 - 65 ] ) were r and omized . All patients received triple immunosuppression with cyclosporine A ( CyA ) , prednisolone ( PRED ) and azathioprine ( AZA ) . In addition , 19 patients received BT563 ( Biotest , Dreieich , Germany ) at a dose of 10 mg/d from day 0 until day 12 . The remaining 21 patients received a placebo infusion at the same days after transplantation . Minimal follow-up for all patients was 3 yr . Patient survival at 3 yr was 74 % in the BT563 group and 90 % in placebo group . Similar results were observed for graft survival . Two acute rejection episodes were detected in the BT563 group and 9 acute rejections ( 5 steroid-resistant ) were observed in the placebo group ( p < 0.034 ) . The incidences of sepsis , pneumonia , cholangitis , urinary tract infections as well as cytomegalo-virus ( CMV ) infections were similar in both groups . Side effects of the BT563 therapy and /or post-transplant lymphoproliferative disease ( PTLD ) were not detected . Quadruple induction therapy with BT563 significantly reduces the incidence of rejection episodes after liver transplantation , while infectious complications and /or PTLD is not increased . Therefore , the anti-IL2 receptor antibody BT563 constitutes a safe and efficient addition to the immunosuppressive induction regimen following OLT Abstract To evaluate the efficacy and safety of oral tacrolimus-based immunosuppressive induction therapy , 130 primary orthotopic liver transplant ( OLT ) recipients were r and omised to treatment in an open , parallel-group , European multicentre trial . Following OLT , patients were immediately administered either tacrolimus ( 0.10 mg/kg ) and prednisolone ( dual therapy group ) or tacrolimus ( 0.06 mg/kg ) in conjunction with prednisolone and azathioprine ( triple therapy group ) both orally . Patient survival at 1 year was 79.4 % for the dual therapy group and 88.7 % for the triple therapy group ( P = 0.194 ) ; 1-year graft survival rates were 76.5 % in the dual therapy group and 80.6 % in the group receiving triple therapy ( P = 0.615 ) . The frequencies of rejection ( dual therapy 42.6 % , triple therapy 50.0 % ; P = 0.482 ) , infection , and other complications ( renal , neurological and glucose metabolic disorders ) were similar in both groups . Tacrolimus whole blood trough concentrations were detectable on days 1 and 2 , respectively , in the dual and triple therapy treatment groups whilst median tacrolimus blood concentrations in the triple therapy group reached levels similar to those in the dual therapy group on postoperative day 11 following a steady increase in dose . After 1 year , 54.4 % of the patients r and omised to dual therapy were receiving tacrolimus monotherapy and only 56.4 % of the patients r and omised to triple therapy continued to receive azathioprine . In conclusion , oral tacrolimus-based immunosuppression is both potent and safe when administered as induction therapy after OLT . Treatment may commence at either 0.06 or 0.10 mg/kg per day , but doses may need to be increased to the latter value within the first 10 days to maintain effective immunosuppression The utility of formulas estimating glomerular filtration rate ( GFR ) in liver transplant patients has not been well described . The purpose is to determine the correlation between the radionuclide GFR ( rGFR ) with formulas commonly used to estimate GFR . This study represented a secondary outcome measure of a multicenter r and omized trial comparing the effectiveness of two immunosuppressive regimens in adult liver transplant patients ( n=148 ) . A total of 68 rGFR were measured , 33 at baseline and at 35 at three months after transplantation . GFR was estimated using 1/Scr and Cockcroft-Gault , MDRD , and Nankivell equations . At both time points assessed , all correlations with rGFR were poor : 1/Scr ( r : 0.17 and 0.25 ) , Cockcroft-Gault ( r : 0.31 and 0.35 ) , MDRD ( r : 0.27 and 0.35 ) , and Nankivell ( r : 0.11 and 0.20 ) . Accepted formulas to estimate GFR correlate poorly with rGFR during the first three months after liver transplantation . Recalibration of these formulas is required to improve the estimation of GFR in liver transplant patients Acute rejection following orthotopic liver transplantation is a common problem despite current immunosuppressive regimens . Ursodeoxycholic acid ( UDCA ) has been shown in small , open-labeled studies to prevent rejection episodes , although its effects on complications such as infections , length of hospital stay , and survival have not been evaluated . We conducted a r and omized , placebo-controlled , double-blind trial to determine if UDCA ( 10 - 15 mg/kg/d ) added to a cyclosporine-based immunosuppressive regimen was associated with a decrease in the incidence of at least one episode of acute cellular rejection . Secondary end-points included determining differences in the total number of rejection episodes , the use of muromonab-CD3 , the incidence of infections , length of hospital stay , and survival at 90 days and 1 year . Fifty-two patients were r and omized , 28 to the treatment group and 24 to the placebo group . During the 3 months of the trial , there was no difference between the placebo and UDCA groups in the number of patients who were rejection-free ; however , there were significantly fewer patients in the treatment group who had multiple episodes of acute rejection ( 0 vs. 6 ; P = .007 ) . Patients in the treatment group experienced a significantly lower incidence of bacterial infections ( 4 % vs. 29 % ; P = .02 ) , shorter hospital stay ( 25 days vs. 34 days ; P = .03 ) , and better 90-day survival ( 100 % vs. 83 % ; P = .04 ) and 1-year survival ( 93 % vs. 79 % ) . The addition of UDCA to a cyclosporine-based immunosuppressive regimen results in significantly fewer patients experiencing multiple episodes of rejection and improved survival at 90 days and at 1 year . The use of UDCA as adjuvant therapy for patients undergoing liver transplantation who are treated with a cyclosporine-based immunosuppressive regimen should be considered Steroids are a mainstay in liver transplantation for induction and maintenance immunosuppression but are associated with significant adverse effects . While prior studies have successfully limited the use of steroids , whether complete steroid avoidance will improve outcomes remains unclear . To further evaluate the need for steroids , consenting patients who underwent liver transplantation between June 2002 and May 2004 were entered into a prospect i ve , r and omized trial to receive either st and ard therapy ( tacrolimus , mycophenolate mofetil , steroid induction/maintenance ) or complete steroid avoidance ( st and ard therapy without steroid induction/maintenance ) . Clinical ly suspected rejection was confirmed by biopsy and treated with pulse steroid therapy . Outcomes were compared on an intention to treat basis . Of the 72 patients enrolled , 36 ( 50 % ) were r and omized to the steroid avoidance group with a mean follow up of 412 + /- 41 days . Donor and recipient characteristics were similar between groups . The steroid avoidance group was more likely to have significant infections ( 52 % vs 28 % , P = .03 ) . There was a trend toward an increased rate of acute rejection ( 25 % vs 14 % , P = .23 ) . Twelve of 36 recipients ( 33 % ) enrolled in the steroid avoidance group later received steroids . The incidence of recurrent hepatitis C was similar between groups . The 1-year patient ( 90 % vs 83 % , P = .44 ) and graft survivals ( 90 % vs 81 % , P = .27 ) were similar between groups . These data suggest complete steroid avoidance in liver transplantation results in acceptable patient and graft survival . However , the potential long-term benefits of steroid avoidance , including a decrease in severity of recurrent hepatitis C , remain under investigation The authors studied 31 liver transplant patients to compare neuropsychiatric side effects of a newer immunosuppressant , FK506 , to cyclosporine A ( CYA ) . Patients were r and omly assigned to either FK506 or CYA . At the 1-week postoperative stage , cognitive status was assessed with the Mini-Mental State Exam , Trailmaking Tests ( TMT ) A and B , Delirium Rating Scale , and a neuropsychiatric symptom checklist . No statistically significant differences were found on any outcome variable between these two drugs , though scores on the TMTs were impaired as compared with published norms . The FK506 patients had moderately impaired TMT scores , whereas the CYA patients had only mild impairment . The patients demonstrate good cognitive recovery at 1 week post-transplantation , with only mild evidence of cognitive impairment This work is a 1-yr interim analysis of a prospect i ve , r and omized , multicenter trial evaluating the effect of corticosteroid-free immunosuppression on hepatitis C virus-positive ( HCV(+ ) ) liver transplant recipients following liver transplantation ( LT ) . Patients received tacrolimus and corticosteroids ( Arm 1 ; n = 80 ) ; tacrolimus , corticosteroids , and mycophenolate mofetil ( MMF ) ( Arm 2 ; n = 79 ) ; or daclizumab induction , tacrolimus , and MMF ( Arm 3 ; n = 153 ) . At 1 yr , 64.1 % , 63.4 % , and 69.4 % of patients achieved the composite primary endpoint of freedom from rejection , freedom from HCV recurrence , and freedom from treatment failure , respectively . Excellent patient and graft survival did not differ significantly among treatment arms . Freedom from HCV recurrence at 1 yr was 61.8 + /- 6.2 % , 60.1 + /- 6.1 % , and 67.0 + /- 4.3 % in Arms 1 , 2 , and 3 , respectively ( P = not significant ) . Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 ( 93.0 + /- 2.2 % vs. 81.9 + /- 4.4 % ; P = 0.011 ) . Multivariate analysis identified acute rejection ( hazard ratio = 2.692 ; P = 0.001 ) and donor age ( hazard ratio = 1.015 ; P = 0.001 ) as significant risk factors for HCV recurrence . HCV recurrence was not influenced by recipient demographics , HCV genotype , or immunosuppression . In conclusion , these results suggest that a corticosteroid-free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV(+ ) liver transplant recipients In this r and omized controlled trial comparing FK-506 to CsA , we report parameters of nephrotoxicity in adult patients surviving > 90 days after orthotopic liver transplant ( OLT ) . Patients r and omized to FK-506 first received 0.15 mg/kg IV/day followed by 0.3 mg/kg PO/day . Doses were modified to avoid toxicity and to achieve FK-506 levels of 0.5 to 1.5 ng/ml . CsA was administered in the usual manner with dose adjustments to whole blood HPLC levels . A pre-OLT glomerular filtration rate ( GFR ) of ≥30 ml/min/1.73/m2 and /or serum creatinine ≤2.0 mg/dl were required for inclusion in the study . GFRs were obtained at post OLT days 28 , 180 , and 360 . Other parameters of renal function evaluated were creatinine , magnesium , serum electrolytes , blood pressure , use of antihypertensives , and magnesium supplements . There were 38 patients in the FK-506 group and 34 in the CsA group . The mean days of follow up for each group was similar : 456 ± 135 days for the FK-506 group and 451 ± 112 days for the CsA group . The mean oral dose for the FK-506 group ranged from 0.13–0.16 mg/kg/day with mean FK-506 levels of 0.6–0.8 ng/ml . In the FK-506 group , there was a significant fall in the pre-transplant GFR from 89 ± 31 ml/min/173 m2 to 43 ± 15 ml/min/173 m2 at day 360 . Similarly , for the CsA group , the pre-transplant GFR of 75 ± 31 ml/min/1.73 m2 fell to 49 ± 17 ml/min/1.73 m2 at day 360 . At each time point studied , there was no significant difference in mean GFR between the two groups . There were no significant differences in the monthly mean values for creatinine , electrolytes , magnesium , or blood pressure between the two groups . Magnesium levels were in the low normal range ( 1.4–1.6 mEq/L ) , and the mean potassium levels in the high normal range ( 4.4–4.7 mEq/L ) . In both groups , a similar number of patients required magnesium supplementation or hypertensive medications . The nephrotoxicity of FK-506 given at low oral doses and with concomitant low levels was comparable to that of CsA. The two drugs were remarkably similar in their spectrum of electrolyte disturbances and incidence of hypertension OBJECTIVE To evaluate the safety and reliability of cyclosporine microemulsion ( CsA-ME ) C(2 ) monitoring and to determine the target level of C(2 ) in Chinese adult liver transplant recipients . METHODS 53 Chinese adult liver transplant recipients were r and omly divided into three groups ( group C(0 ) , n = 17 ; group high level C(2 ) , n = 18 ; group low level C(2 ) , n = 18 ) . Blood chemistry reflecting heart , liver and renal function and CsA level were examined at certain interval during follow-up . The change of immune status and episodes of rejection were also observed closely . RESULTS The group low level C(2 ) had the lowest CsA oral dose ( 2.51 + /- 0.37 mg/kg/d ) , and had significant difference compared with the other groups ( P < 0.01 ) . The best liver , heart and renal function was observed in group low level C(2 ) . The CD(4)(+)/CD(8)(+ ) ratio of group low level C(2 ) was 1.04 + /- 0.68 , which had no significant difference with C(0 ) group . The rejection incidence of the three groups had no significant difference . group low level C(2 ) had highest clinical benefit ratio ( 72.22 % ) , while the clinical benefit of group high level C(2 ) is the lowest ( 11.11 % ) . CONCLUSIONS With rational target level , C(2 ) monitoring can show us the proper oral dose of CsA which can decrease the side effects remarkably without rejection episodes increasing . The target level of C(2 ) in Chinese adult liver transplant recipients might be : 600 - 800 ng/ml 1 to 6 months posttransplant , 400 - 600 ng/ml 7 - 12 months posttransplant Everolimus ( EVR ) is a semi-synthetic mammalian target of rapamycin inhibitor currently under development for liver transplantation ( LTx ) in combination with reduced exposure tacrolimus ( rTAC ) . The relative potency of EVR was assessed in order to generate evidence for concomitant EVR+rTAC exposure in LTx recipients ( LTxR ) . Twelve month data from study H2304 ( NCT00622869 ) , a 24-month , r and omized , multicenter study in 719 de novo LTxR comparing EVR+rTAC to st and ard TAC demonstrated superior renal function and comparable efficacy , including fewer and less severe biopsy proven acute rejections with EVR+rTAC . Relative potency ( p ) of EVR was defined as factor by which the effect of 1 ng/mL of EVR must be multiplied to get comparable immunosuppression as with TAC : p = ( TACcon - TACred)/EVRred . Relative efficacy of EVR in 4 different subpopulatlons was consistently 0.64 , 0.60 , 0.69 , and 0.62 , respectively . This assessment determined the relative potency of EVR as 0.64 compared to TAC in LTx indicating that EVR and TAC are not equipotent per ng/mL exposure . Knowledge about relative potency will help to rationalize co-exposure of EVR and TAC In an effort to determine the total one-year cost of liver transplantation , the underlying drivers of that cost , and any cost differences between alternative immunosuppressive regimens , an analysis was performed comparing the average one-year posttransplant charges of 322 patients participating in the " U.S. Multi-center Prospect i ve R and omized Trial Comparing FK-506 to Cyclosporine in Liver Transplantation . " Total one-year inpatient charges including all readmissions were examined . Professional fees and outpatient charges were excluded . Costs for tacrolimus drug and blood assays were assumed to be equal to those in the CsA group . For patients completing the study , the tacrolimus group had an average length of stay and average one-year cost seven days ( P = .06 ) and $ 19,290 ( P = .05 ) lower than the CsA group . The difference in rejection profiles between the two arms seems to largely account for the lower costs . The tacrolimus arm consistently had fewer patients in the more severe rejection groups . Increased incidence and severity of rejection were directly related to higher average lengths of stay and costs of transplantation ( P < .001 ) . Tacrolimus immunosuppression during the first year after liver transplantation is more cost-effective than CsA in achieving similar patient and graft survival rates . Differing incidence and severity of rejection can dramatically affect the first-year cost of liver transplantation BACKGROUND Reducing immunosuppression not only reduces complications but also may lessen recurrent hepatitis C virus ( HCV ) infection after liver transplantation . PATIENTS / METHODS HCV-infected cirrhotic patients r and omised to tacrolimus monotherapy ( MT ) or triple therapy ( TT ) using tacrolimus 0.1 mg/kg/day , azathioprine 1 mg/kg/day , and prednisolone 20 mg/day , tapering over 3 months . RESULTS Twenty-seven patients ( MT ) and 29 (TT)--median follow up 661 days ( range , 1 - 1603 ) . Rejection episodes ( protocol /further biopsies ) within first 3 months and use of empirical treatment were evaluated . New rejection was diagnosed if repeat biopsy ( 5-day interval ) did not show improvement . Treated rejection episodes : 20 MT ( 15 biopsy-proven ) vs. 24 TT ( 21 biopsy-proven ) , with 19 ( MT ) vs. 24 ( TT ) methylprednisolone boluses . Overall : 35 episodes ( MT ) and 46 ( TT ) . Fewer MT patients had histological rejection ( 70 % ) than TT patients ( 86 % ) , with fewer episodes of rejection ( 18.5 % vs. 10 % ) , and more moderate rejection ( 22 % vs. 41 % ) . The MT group had higher early tacrolimus levels . Rates of renal dysfunction , retransplantation , and death were not significantly different . CONCLUSION Tacrolimus monotherapy is a viable immunosuppressive strategy in HCV-infected liver transplant recipients We previously reported our experience of infectious complications occurring following liver transplantation ( OLT ) under an experimental immunosuppressive agent FK 506.1 In February 1990 we initiated a r and omized trial comparing this new drug to cyclosporine ( CyA ) in patients undergoing their first OLT . In this report we analyzed the infectious complications in the first 110 patients enrolled in this study Some clinical studies in liver transplantation have recently reported safety advantages and similar acute rejection rates with early steroid withdrawal . The aim of this study was to evaluate the efficacy and safety of an immunosuppressive regimen with steroid withdrawal at day 14 . A multicenter , 1-year , comparative , double blind , placebo-controlled study was performed . Patients undergoing a first cadaveric liver transplantation were recruited and all received basiliximab + cyclosporine + intravenous methylprednisolone . Patients without severe postoperative complications were r and omized at day 7 to receive a maintenance regimen with Neoral ( cyclosporine ) + prednisolone ( group 1 ) or without steroids ( Neoral + placebo ; group 2 ) , after a 7-day blinded oral steroid tapering period . A total of 174 patients were r and omized at day 7 ( group 1 : n = 90 ; group 2 : n = 84 ) . The incidence of biopsy-confirmed and treated acute rejection at 6 months was 38.1 % in group 2 vs. 24.4 % in group 1 ( P = .03 ) with a trend for a higher incidence of Grade II / III acute rejection ( 28.6 % vs. 18.9 % ; P = .12 ) . Changes from baseline were similar with regard to metabolic parameters ( glycemia , total cholesterol , and triglycerides ) . A trend toward a better glucose tolerance was observed , as fewer patients received an antidiabetic treatment in the placebo group ( 2 vs. 10 ) . In conclusion , this first double-blind , placebo-controlled study of steroid withdrawal at day 14 showed a higher incidence of acute rejection , only balanced by a trend of a lower need of antidiabetic treatment This is the first multicenter , r and omized , open-label study to compare the efficacy and safety of cyclosporine A microemulsion ( CsA-ME ) ( Neoral , Novartis , Basel , Switzerl and ) with C2 monitoring versus tacrolimus in de novo liver transplant recipients . Patients were stratified according to hepatitis C virus status and r and omized to receive CsA-ME ( n= 250 ) or tacrolimus ( n= 245 ) with steroids , with or without azathioprine . The primary endpoint was the incidence of biopsy-proven acute rejection ( BPAR ) at 3 months . Secondary endpoints included death or graft loss and safety evaluations at 6 months . The incidence of BPAR at 3 months was 26 % in the CsA-ME group and 24 % in the tacrolimus group ( not significant ) . At 6 months , 89 % of patients receiving CsA-ME and 88 % of patients receiving tacrolimus were alive with a functioning graft . Among the hepatitis C virus-positive patients , there was no difference in BPAR , but death or graft loss was more frequent in those receiving tacrolimus ( 15 % vs. 6 % , P < 0.05 ) . Diabetes mellitus ( 14 % vs. 7 % , P < 0.02 ) and diarrhea ( 29 % vs. 14 % , P < 0.001 ) were significantly more often reported in patients receiving tacrolimus . The incidence of hypertension was similar in both groups . At 6 months , the median total cholesterol was 4.7 mmol/L ( 2.9–7.4 mmol/L ) in the CsA-ME arm versus 4.3 mmol/L ( 2.5–6.4 mmol/L ) in the tacrolimus arm ; the median serum creatinine was 106 μmol/L ( 52–238 μmol/L ) in the CsA-ME arm versus 103 μmol/L ( 44–477 μmol/L ) in the tacrolimus arm . Efficacy is equivalent with CsA-ME using C2 monitoring or tacrolimus in liver transplant recipients . The incidence of adverse events is comparable except for a significantly higher incidence of diabetes mellitus and diarrhea in the tacrolimus group . Both agents are effective primary immunosuppressants in liver transplant recipients This open-label , r and omized study compared the efficacy of a regimen of corticosteroids and tacrolimus ( st and ard therapy group , n = 79 ) with a regimen of daclizumab induction therapy in combination with mycophenolate mofetil and tacrolimus ( modified therapy group , n = 78 ) in primary liver transplant recipients . The primary endpoint was biopsy-proven acute rejection ( BPAR ) at 24 weeks . Secondary endpoints included time to rejection and patient and graft survival . The incidence of BPAR was significantly reduced in the modified therapy group compared to the st and ard therapy group ( 11.5 % versus 26.6 % , respectively , P = 0.017 ) . The time to rejection was significantly shorter in the st and ard therapy group compared with the modified therapy group ( P = 0.044 ) . There was no significant difference between groups in patient or graft survival . Hepatitis C virus-positive patients exhibited no differences from hepatitis C virus-negative patients with respect to the incidence of BPAR . A steroid-sparing regimen of daclizumab , mycophenolate mofetil , and tacrolimus was effective and well tolerated in the prevention of BPAR in adult liver transplant recipients in comparison with a st and ard regimen of tacrolimus and steroids OBJECTIVE To investigate the effects of tacrolimus-based immunosuppression regimens after orthotopic liver transplantation and search a reasonable regimen of combination therapy and suitable blood concentration of tacrolimus . METHODS Ninety-four adult recipients of cadaveric livers were r and omly divided into 3 groups to undergo different tacrolimus-based immunosuppression regimens : dual ( tacrolimus + glucocorticoid ) , triple [ tacrolimus + mycophenolate mofetil ( MMF ) + glucocorticoid ] ; quadruple [ tacrolimus + MMF + glucocorticoid in addition of induction treatment by daclizumab ] . The efficacy and safety of the 3 groups 6 months after the transplantation were compared . RESULTS The frequencies of acute rejection were 25.9 % , 11.1 % , and 7.5 % for the dual , triple , and quadruple therapy groups , that of the quadruple therapy group being significantly lower than that of the dual therapy group ( P = 0.038 ) . There were no significant differences in the rates Three months after transplantation , the levels of ALT and total cholesterol of the dual therapy groups were significantly higher than those of the quadruple therapy group ( P(ALT ) = 0.011 , P(Tch ) = 0.002 ) . Within the first month post-operatively the concentration of tacrolimus of the triple therapy group could be controlled at the level 8 ng x ml(-1)-13 ng x ml(-1 ) . CONCLUSIONS Quadruple tacrolimus-based immunosuppression regimen is the most effective and safest , followed by the triple therapy and dual therapy . Low-dose tacrolimus combination therapy provides an effective protection to the liver graft with mild drug toxicity to the patient New immunosuppressive agents and regimens should be evaluated specifically in living donor liver transplant patients due to potential clinical and pharmacokinetic differences between deceased donor and living donor transplant recipients . The analysis presented here is the first direct comparison of clinical outcomes using cyclosporine microemulsion ( CsA-ME ) with monitoring of blood concentration at 2 hours postdose ( C2 ) and tacrolimus-based immunosuppression in living donor liver transplantation . The analysis was conducted on the data provided by the 39 recipients of a living donor transplant out of the 495 patients enrolled in a 6-month , r and omized , prospect i ve , multicenter , open-label study ( LIS2 T ) . Patients were r and omized to CsA-ME ( C2 monitoring ) or tacrolimus ( monitoring of predose trough drug blood level [ C0 ) ] ) and were administered corticosteroids with or without azathioprine . Twenty-three living-donor patients received CsA-ME and 16 received tacrolimus . By month 6 , 9 % of patients receiving CsA-ME and 19 % of those receiving tacrolimus had lost their graft or died ( not significant [ NS ] ) . Nine episodes of biopsy-proven acute rejection were reported : 4 in the CsA-ME group ( 17 % ) and 5 in the tacrolimus cohort ( 31 % , NS ) . There were no significant differences in any safety parameter between groups . The most frequently reported serious adverse events were infections , which occurred in 14 patients in the CsA-ME group ( 61 % ) and 13 patients in the tacrolimus arm ( 81 % , NS ) . Twelve patients in the CsA-ME arm ( 52 % ) and 5 in the tacrolimus arm ( 31 % , NS ) discontinued the study prematurely . In conclusion , CsA-ME C2 monitoring or tacrolimus both offer effective protection against rejection in living donor liver transplants while maintaining a good safety profile BACKGROUND Chronic kidney disease ( CKD ) has emerged as a significant cause of morbidity and a risk factor for mortality after orthotopic liver transplantation ( OLT ) . The use of calcineurin inhibitor (CNI)-based immunosuppression is an important etiologic factor for developing CKD . CNI discontinuation or minimization protocol s with replacement of the CNI with non-nephrotoxic drugs , such as mycophenolate mofetil ( MMF ) or sirolimus ( SRL ) , may have the potential to preserve or recover renal function . PATIENTS AND METHODS In this prospect i ve , r and omized , single-center study with CNI discontinuation , OLT recipients with CKD ( measured glomerular filtration rate [ GFRm ] 15 - 45 mL/min/1.73 m(2 ) ) were r and omized to either SRL or MMF-based immunosuppression . The main objective was to study the effect of CNI discontinuation on renal function . Secondary aims were to assess the frequency of biopsy-proven acute rejection episodes ( BPAR ) and adverse events ( AE ) . Renal function was followed with GFRm using 51-Chromium EDTA clearance at baseline , 3 months , and 1 year . Patients were stratified according to baseline GFRm > versus < 30 mL/min/1.73 m(2 ) . The 25 patients were enrolled for MMF ( n = 13 ) or SRL ( n = 12 ) . The median age at inclusion was 59 years ( range , 25 - 66 ) and the median number of years after OLT was 4.4 ( range , 1 - 13 ) . Twenty-two patients were followed up for a year ; MMF ( n = 12 ) and SRL ( n = 10 ) . RESULTS Mean GFRm for the whole cohort ( n = 25 ) was 31+/-8 mL/min/1.73 m(2 ) at baseline . After 3 months the GFRm ( n = 23 ) increased to 40+/-10 mL/min/1.73 m(2 ) ( P = .0001 ) and at 1 year 42 + /- 11 mL/min/1.73 m(2 ) ( n = 22 ) . There was not significant difference between the MMF and the SRL study arms . The cohort ( n = 8) with baseline GFRm < 30 mL showed a 63 % ( P = .003 ) increased filtration after 1 year . There was no significant difference in the frequency or severity of AE between the study arms with the exception of oral ulcerations and persistent hypertriglyceridemia in the SRL group . Two deaths occurred , 1 in each study arm , both probably unrelated to the change in immunosuppression . There were no BPAR episodes . CONCLUSION CNI discontinuation and replacement with either MMF or SRL result ed in a significant improvement in renal function even in those patients with severe CKD . The protocol was effective with no acute rejection episodes . The SRL arm showed a higher frequency of oral apthous ulcerations and hypertriglyceridemia . Future studies addressing long-term renal function after CNI discontinuation are needed Background . In 2001 , we published early results of a prospect i ve r and omized trial of 71 patients who received either steroids or rabbit antithymocyte globulin ( RATG ) for orthotopic liver transplantation ( OLT ) . We now report follow-up on these patients and additional patients undergoing steroid-free OLT . Methods . A total of 119 adult OLT recipients were prospect ively r and omized to receive either methylprednisolone 1,000 mg followed by a 3-month steroid taper or a steroid-free regimen of RATG 1.5 mg/kg during the anhepatic phase followed by a 1.5 mg/kg dose on posttransplant day 1 . Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil in both groups . Mycophenolate mofetil was weaned over 3 months in the first 71 patients and over 2 weeks in the last 48 patients , achieving tacrolimus monotherapy by 2 weeks posttransplant . Subsequently , a group of 24 sequential OLT recipients received the steroid-free ( RATG ) protocol . Endpoints of the study were survival , rejection , infectious complications , posttransplant diabetes , and recurrent hepatitis C virus . Results . One-year patient survival was 85 % in each group of the prospect i ve r and omized trial with a mean follow-up of 18.5 months . One-year graft survival was 82 % in the RATG group and 80 % in the steroid group ( P = not significant ) . Patient and graft survival of the 24 nonr and omized RATG patients was 96 % with a mean follow-up of 3 months . The incidence of rejection was not significantly different ; however , 50 % of the patients in the steroid group required pulse steroids to reverse the rejection compared with only one patient ( 1.6 % ) in the RATG group ( P = .03 ) . The incidence of cytomegalovirus infection ( P < .05 ) and posttransplant diabetes was higher in the steroid group ( P = .03 ) . There was a trend toward decreased severity of hepatitis C virus in the RATG group . Conclusions . Steroid-free liver transplantation using RATG and early tacrolimus monotherapy effectively reduces immunosuppression-related complications with excellent survival Seventy-nine hepatic allograft recipients were r and omized to receive either conventional immunosuppression , including cyclosporine , azathioprine , and steroids ( 41 patients ) , or investigational therapy in which OKT3 replaced cyclosporine during the first postoperative week ( 38 patients ) . Early rejection occurred in 29 patients ( 71 % ) in the conventional group and 15 patients ( 39 % ) in the OKT3 group . Posttransplantation renal dysfunction occurred in 12 patients ( 29 % ) in the conventional group and 6 patients ( 16 % ) in the OKT3 group . Mean initial hospital stay was 34.1 + /- 18.8 days in the conventional group compared with 29.1 + /- 16.8 days in the OKT3 group . Cumulative patient survival ( mean follow-up , 17.8 + /- 7.1 months ) was 73.2 % ( 30/41 ) for the conventional group and 84.2 % ( 32/38 ) for the OKT3 group . Prophylactic OKT3 is indicated especially for liver allograft recipients with other complicating conditions that make management of early rejection unusually difficult BACKGROUND & AIMS Robust clinical data evaluating fibrosis progression in hepatitis C virus ( HCV ) liver transplant patients receiving an mTOR inhibitor vs. calcineurin inhibitor ( CNI ) are lacking . To evaluate fibrosis progression in maintenance liver transplant patients receiving everolimus- or CNI-based immunosuppression . METHODS In a r and omised , multicentre , open-label study , 43 maintenance liver transplant patients with recurrent HCV infection were r and omised to continue CNI-based immunosuppression or switch to everolimus . RESULTS For patients with biopsy data at month 12 , mean Ishak-Knodell fibrosis score at baseline was 2.6 ± 0.9 ( n = 14 ) with everolimus vs. 1.9 ± 1.1 ( n = 18 ) with CNI ( P = 0.043 ) , and 1.9 ± 1.2 vs. 2.2 ± 1.3 at month 12 . Ishak-Knodell fibrosis score decreased from baseline to month 12 by a mean of -0.7 ± 1.1 with everolimus , but increased by 0.2 ± 1.2 with CNI ( P = 0.046 ) . No acute rejection or graft losses occurred up to month 12 . Estimated GFR at month 12 was 65.6 ml/min/1.73 m² with everolimus and 62.2 ml/min/1.73 m² with CNI [ mean difference 3.4 ml/min/1.73 m² compared to CNI control group , 95 % CI -4.9 , 11.8 ml/min/1.73 m² , P = 0.411 ( analysis of covariance adjusting for baseline GFR ) ] . Adverse events occurred in 95.5 % of everolimus patients and 71.4 % of CNI patients ( serious adverse events 31.8 % and 0.0 % , respectively ) . Adverse events led to everolimus discontinuation in five patients ( 22.7 % ) . CONCLUSIONS This exploratory study suggests that conversion from CNI to everolimus reduces progression of liver fibrosis , and preserves renal function without jeopardising efficacy in liver transplant recipients with recurrent HCV , but is associated with a higher incidence of adverse events and serious adverse events . These preliminary findings merit examination in a larger trial Everolimus is a macrolide immunosuppressive agent with known consistent absorption . In this double-blind study , we examined the safety and tolerability of everolimus vs. placebo in de novo liver transplant recipients . One hundred and nineteen liver allograft recipients were r and omized to 1 of 4 groups : everolimus 0.5 mg bid , everolimus 1.0 mg bid , everolimus 2 mg bid , or placebo . Patients received oral cyclosporine to achieve a target trough level of 150 - 400 ng/mL in combination with prednisone . Primary and secondary endpoints of safety , tolerability , and efficacy were determined at 12 months , and patients were followed through 36 months . There was a trend toward fewer treated acute rejections in the everolimus group than in the placebo group : everolimus 0.5 mg : 39.3 % ; everolimus 1.0 mg : 30.0 % ; everolimus 2 mg : 29.0 % ; placebo : 40.0 % ( P = not significant ) . Adverse events were higher in everolimus-treated patients especially at the 4-mg/day dose , but there was no difference in the incidence of thrombocytopenia or leukopenia between all groups and renal function as determined by serum creatinine , and creatinine clearance remained stable to 36 months in everolimus-treated patients . Mean cholesterol and triglycerides increased from baseline in all treatment groups , and maximum levels were seen at 6 months . In conclusion , this study demonstrates that everolimus in combination with oral cyclosporine had an acceptable safety and tolerability profile , paving the way for additional studies in this transplant indication Neurotoxicity represents a serious complication following orthotopic liver transplantation . Neurotoxicity may be evoked by various perioperative factors or develop due to drug-specific toxicity of immunosuppression . We evaluated the incidence of neurotoxicity in 121 patients , 61 r and omly assigned to FK506 and 60 to CsA-based immunosuppression . The incidence of moderate or severe neurotoxicity was markedly higher in patients treated with FK506 in the early postoperative period ( 21.3 % vs. 11.7 % in patients receiving CsA ) , after retransplantation ( 100 % vs. 0 % in patients receiving CsA ) , and late ( 8 of 10 patients ; P < or = 0.05 vs. CsA ) . Furthermore late neurotoxicity was highly associated with severe infections and MOFS , which had a lethal outcome in more than 50 % of the patients . Patients who subsequently died developed neurologic symptoms in 67 % of the cases . These patients also experienced moderate or severe neurotoxicity significantly more often in the early postoperative period compared with patients with a successful outcome ( 50 % vs. 17.3 % ; P < or = 0.01 ) . However , various blood and serum parameters , including ALT , bilirubin , urea , creatinine and glucose , when analyzed alone or in multivariate fashion , also correlated significantly with the incidence and severity of early postoperative neurotoxicity , indicating that neurotoxicity following LTX may be caused by various factors and is not exclusively a drug-specific side effect of immunosuppression Background We conducted a r and omized multicenter open-label trial in de novo liver transplant recipients to assess the feasibility and potential benefit of a corticosteroid (CS)-free regimen coupled with tacrolimus ( Tac ) and dose-intensified mycophenolate mofetil ( MMF ) further adjusted individually . Methods Adult liver transplant recipients were r and omized on the day of transplantation to a CS-free regimen with Tac and MMF starting at 3 g/d and dose adjusted from day 5 according to mycophenolic acid ( MPA ) exposure ( arm A ) or a regimen with CS maintained up to 6 months , Tac and fixed-dose MMF ( 2 g/d ) ( arm B ) . The primary end point was the proportion of patients who experienced treated biopsy-proven acute rejection ( BPAR ) during the first year posttransplant . Results One hundred eighty-seven patients were r and omized , and 174 comprised the per- protocol population ( 87 in each arm ) . The primary objective of noninferiority was met : 7 patients in arm A ( 8 % ) and 8 in arm B ( 9 % ) experienced treated BPAR in the first year . Two patients in arm A ( 2 % ) and 5 in arm B ( 6 % ) lost their graft , and 12-month patient survival was similar in both arms ( 90.8 % vs 89.8 % ; P = 0.86 ) . Adverse events were comparable between arms , except for a lower incidence of de novo diabetes ( 19.8 % vs 32.6 % , P = 0.049 ) and a higher incidence of leukopenia less than 2000/mm3 ( 28.6 % vs 9.8 % ; P = 0.001 ) and neutropenia ( 26.7 % vs 7.9 % ; P < 0.001 ) in arm A. Conclusions Mycophenolate mofetil at intensified and individually adjusted dose in combination with Tac in de novo liver transplant recipients allows CS discontinuation from day 1 posttransplant with good tolerance and very low rejection incidence This pilot trial was design ed to assess the safety and efficacy of SRL in liver transplant recipients with renal dysfunction . Forty patients with renal dysfunction ( 24-hr CrCl 40–80 mL/min ) were r and omized to be withdrawn from the calcineurin inhibitor ( CNI ) and receive sirolimus ( SRL ) or to continue CNI ( control arm ) . Improvement in 24-hour CrCl was seen in the SRL arm at 3 months ( 75 mL/min SRL vs. 56 mL/min control , P=0.012 ) , whereas at 12 months there was a trend toward improvement in the SRL arm ( 72 mL/min SRL vs. 58 mL/min control , P=0.09 ) . Two patients , one in each arm , developed steroid-sensitive rejection . Side effects of SRL were limited and included hyperlipidemia requiring treatment ( 15 % ) , pruritis ( 5 % ) , and mouth sores ( 25 % ) . In this trial , SRL-based immunosuppression was a safe alternative to CNI . Although early improvements were observed , withdrawing CNI and replacing it with SRL did not result in a statistically significant improvement in renal function at 12 months of follow-up To assess the efficacy and safety of a primary immunosuppressive regimen with tacrolimus ( Tac ) and low-dose mycophenolate mofetil ( MMF ) without steroids and to determine the exposure to mycophenolic acid ( MPA ) in the early postoperative period , we performed a single-center , r and omized 1:1 , open-label , controlled study planned to be 60 liver transplantation patients r and omized into 2 groups : group A , tacrolimus + MMF ( 750 mg orally twice a day ) ; and group B , tacrolimus + MMF ( 750 mg orally twice a day ) + steroids . After an interim analysis by the ethical committee patient enrollment was stopped . Data from 30 patients ( 12 in group A and 18 in group B with a mean follow-up period of 31 + /- 7 months ) showed a patient survival rate of 91.7 % in group A and 100 % in group B and a graft survival rate of 91.7 % and 88.9 % , respectively . Nine patients ( 75 % ) in group A suffered an acute rejection episode , whereas in group B only 3 patients ( 16.7 % ) showed acute rejection ( P = .002 ) . All rejection episodes occurred in both groups at 1 week after transplantation . The difference in histological grading was statistically significant ( P = .021 ) . The toxicity profiles were similar in both groups . A primary immunosuppressive regimen based on Tac and low-dose MMF without steroids is safe but unable to prevent acute rejection at 1 week after transplantation even if early acute rejection does not affect the outcome in terms of morbidity and graft or patient survival Cyclosporine ( CsA ) and tacrolimus ( FK506 ) have recently been reported to inhibit canalicular transport of bile acids in vitro and thereby possibly induce cholestasis . A relative reduction of chenodeoxycholic acid ( CDCA ) has been observed after liver transplantation when CsA is used as immunosuppressant . We tested the hypothesis that CsA induces cholestasis and reduces CDCA secretion as compared with treatment with monoclonal antibodies ( OKT3 ) , and that CsA differs from FK506 with regard to its effects on biliary lipid secretion . Bile flow , biliary lipid secretion rates , and biliary bile acid composition were determined during the first 10 days after transplantation in 29 liver transplant recipients . Two prospect i ve r and omized studies were performed that compared CsA and OKT3 and compared CsA- and FK506-based regimens . In study 1 , bile acid output averaged 0.75+/-0.15 micromol/min in the CsA I group and 0.54+/-0.11 micromol/min in the OKT3 group on postoperative day 1 . Bile flow and bile acid output then increased , and there was no significant difference between the two groups . The relative proportion of CDCA decreased to the same extent in both groups . In study 2 , mean bile acid outputs on postoperative day 1 were 0.57+/-0.26 micromol/min and 0.55+/-0.15 micromol/min in the CsA 2 and FK506 groups , respectively . The following increase in bile acid secretion was significantly larger in the FK506 group . After transplantation , the relative proportion of CDCA decreased with time in both groups , but the reduction was more rapid in the FK506 group . In conclusion , CsA did not inhibit bile secretion during short-term treatment after liver transplantation . Compared with patients given CsA-based treatment , patients with FK506-based treatment recovered bile secretion more rapidly There are several case reports in the literature that describe cardiac complications in the first few weeks after orthotopic liver transplantation ( OLT ) in patients receiving tacrolimus as their primary immunosuppressive therapy . In this study , we investigated the cardiac function of patients on tacrolimus ( T ) compared with those on cyclosporin ( C ) ( Neoral ; Novartis , Basel , Switzerl and ) immunosuppression , after OLT , in a prospect i ve r and omized trial . We r and omized 40 adult patients with cirrhosis to either T or C with azathioprine and prednisolone immunosuppression and followed up on them for 3 months after OLT . All had detailed clinical , biochemical , electrocardiographic and echocardiographic assessment s at regular intervals . Abnormalities in cardiac function were common after OLT and significant deterioration in left ventricular diastolic function was demonstrable up to 3 months in both patient groups . Cardiac function was similar in the T and C arms and no significant electrocardiographic differences were observed , although reduced heart rate variability ( HRV ) and higher mean serum brain natriuretic peptide ( BNP ) levels were identified in the T group . The percentage increase in posterior wall thickness was higher in the T group . Cardiac dysfunction as shown by worsening echocardiographic measures of left ventricular diastolic function and by clinical cardiac events is common in the first 3 months after OLT in patients with cirrhosis . HRV and BNP values in the T group were worse than in the C group , but this was not translated to an increase in cardiac clinical events in this study Early steroid withdrawal after liver transplantation ( LT ) is desirable in order to reduce steroid side effects . Between February 2000 and August 2004 , 110 patients after LT were included in this prospect i ve , r and omized , double‐blind , placebo‐controlled trial . R and omization was performed before LT . In all patients , tacrolimus was used without induction therapy . All patients received methylprednisolon for 14 days , thereafter a double‐blinded medication containing either placebo ( n = 56 ) or methylprednisolon ( n = 54 ) for 6 months , which was completely stopped thereafter . End points were patient and graft survival , acute and chronic rejection , and incidence of steroid side effects during the first year after LT . One‐year patient survival was 85.7 % ( placebo ) and 88.8 % ( steroid ) ( p = 0.572 ) . Twenty‐seven ( 48.2 % ) and 19 ( 35.2 % ) patients experienced acute rejection ( placebo versus steroid , respectively ; p = 0.116 ) . Two patients in the placebo group but none in the steroid group experienced chronic rejection ( p = 0.257 ) . The rates of side effects were ( placebo versus steroid , respectively ) : CMV infection 25 % versus 33 % ( p = 0.336 ) , post‐transplant diabetes 30 % versus 53 % ( p = 0.024 ) , hypertension 39 % versus 52 % ( p = 0.248 ) , hypercholesterolemia 10 % versus 41 % ( p = 0.002 ) and hypertriglyceridemia 32 % versus 54 % ( p = 0.046 ) . In conclusion , early steroid withdrawal after LT is feasible under tacrolimus monotherapy without increased rejection rates and with a lower rate of side effects Background . Liver transplantation ( LTX ) recipients with renal dysfunction may benefit from mycophenolate mofetil ( MMF ) and reduction or discontinuation of nephrotoxic calcineurin inhibitors ( CNI ) . The authors report the first r and omized , multicenter pilot studies of this approach ( one study for patients on cyclosporine [ CsA ] and one for those on tacrolimus [ Tac ] ) . Methods . Patients 3 to 27 months post-LTX with greater than 20 % reduced renal function since LTX , and creatinine 1.8 to 4.0 mg/dL , creatinine clearance 20 to 60 mL/min , or both , were r and omized to discontinuation ( group 1 ) or 50 % reduction ( group 2 ) of CNI dose , together with MMF 1.5 g administered twice daily and prednisone . Endpoints included measured glomerular filtration rate ( GFR ) 52 weeks after study entry and biopsy-proven rejection . Results . In the CsA and Tac trials , 15 and 12 patients , respectively , completed the 52-week follow-up . In the CsA trial , the mean GFR at baseline and week 52 were 35.0 and 57.8 mL/min ( > 15 % improvement , five of six ; unchanged , one of six ) for group 1 and 46.0 and 63.8 mL/min ( > 15 % improvement , four of nine ; unchanged , three of nine ; > 15 % deterioration , two of nine ) for group 2 . In the Tac trial , GFRs were 55.4 and 56.0 mL/min ( > 15 % improvement , two of five ; unchanged , three of five ) for group 1 and 46.7 and 60.2 mL/min ( > 15 % improvement , four of seven ; unchanged , three of seven ) for group 2 . Mild or moderate rejection occurred in 38 % and 9 % of patients in groups 1 and 2 of the CsA trial and in 14 % of each group of the patients in the Tac trial . Conclusions . These pilot studies show that in LTX recipients with renal dysfunction , MMF allows CNI dose reduction or discontinuation , improving or stabilizing GFR in most patients BACKGROUND Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation . However , the use of polyclonal antibody preparations ( e.g. antithymocyte globulin [ ATG ] ) is associated with side effects such as fever and tachycardia . To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor ( BT563 ) in comparison with ATG as part of a quadruple induction regimen , a prospect i ve , r and omized study was conducted . METHODS Eighty consecutive adult recipients of primary orthotopic liver transplants were r and omized to receive either BT563 ( 10 mg/day ; days 0 - 12 ; n=39 ) or ATG ( 5 mg/kg/day ; days 0 - 6 ; n=41 ) in addition to the st and ard immunosuppressive protocol consisting of cyclosporine , and prednisolone , and azathioprine . RESULTS Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes ( 3 vs. 11 ; P<0.025 ) and also significantly fewer drug-related side effects ( 4 vs. 18 , P<0.038 ) when compared with patients treated with ATG . The incidence of infectious complications was not different between the two groups . Patient survival did not differ significantly between the two groups ( 84.6 % at 1 , 2 , and 3 years in the BT563 group and 90.2 % at 1 year and 87.8 % at 2 and 3 years for the ATG group ) . Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels . However , no differences were observed in long-term follow-up between the two groups . CONCLUSIONS Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG The aim of this study was to evaluate the success of steroid ( PRED ) withdrawal due to replacement by mycophenolate mofetil ( MMF ) in orthotopic liver transplant ( OLT ) recipients with autoimmune hepatitis ( AIH ) . Thirty patients with AIH > 12 months after OLT r and omized to receive either PRED and tacrolimus ( TAC ) or MMF and TAC were followed for 24 months . Withdrawal of steroids showed no difference regarding graft and patient survival . Also we demonstrated significantly lower glucose levels with lower HbA1c and a reduced need for insulin as well as a significantly lower serum cholesterol in the MMF group . Patients without steroids showed a lower incidence of osteopenia . Maintenance therapy in OLT patients with AIH may be performed safely using MMF instead of prednisone Introduction . Long-term steroid administration may predispose liver transplant recipients to infectious and metabolic complications . Maintaining effective immunoprophylaxis while minimizing the negative consequences of steroid therapy could be a key factor in improving clinical outcomes . Methods . Six hundred two patients were r and omized to receive tacrolimus ( TAC ) immunosuppression with a single-steroid bolus and two doses of daclizumab ( DAC ) or mycophenolate mofetil ( MMF ) . Results . The incidence of biopsy-proven acute rejection was 19.7 % in the TAC/DAC group and 16.2 % in the TAC/MMF group ( ns ) . Three-month patient and graft survival were similar . Steroid use at month-3 was low at 5.5 % in the TAC/DAC group and 3.9 % in the TAC/MMF group . Significantly higher incidences of causally related adverse events ( AEs ) and significantly more dose modifications , interruptions , or discontinuations due to an AE were reported with TAC/MMF . Study withdrawal due to leucopenia was significantly higher with TAC/MMF ( 0.0 % vs. 1.7 % . P≤0.05 ) . AEs were generally reported less frequently in the TAC/DAC group . However , specifically headache and supraventricular arrhythmia were significantly higher with TAC/DAC , whereas leucopenia and bacterial infection were significantly higher with TAC/MMF . Laboratory indices of renal function were similar , and increases in serum lipids were negligible in both groups . Incidences of de novo diabetes mellitus ( ≥2 fasting plasma glucose values ≥7.0 mmol/L ) were low at 9.5 % ( TAC/DAC ) and 11.0 % ( TAC/MMF ) . Conclusion . Both TAC-based regimens allowed optimization of immunoprophylaxis while eliminating some of the negative consequences associated with steroids . Efficacy outcomes were comparable ; however , TAC monotherapy after DAC induction was associated with significantly less leucopenia and less bacterial infection than a dual regimen incorporating MMF BACKGROUND Tacrolimus ( TAC ) and mycophenolate mofetil ( MMF ) are currently approved immunosuppressants for prevention of rejection in liver transplantation ( LTx ) . They have different modes of action and toxicity profiles , but the efficacy and safety of MMF in primary liver transplantation with TAC has not been determined . METHODS An Institutional Review Board-approved , open-label , single-center , prospect i ve r and omized trial was initiated to study the efficacy and toxicity of TAC and steroids ( double-drug therapy ( D ) ) versus TAC , steroids , and MMF ( triple-drug therapy ( T ) ) in primary adult LTx recipients . Both groups of patients were started on the same doses of TAC and steroids . Patients r and omized to T also received 1 gm MMF twice a day . RESULTS Between August 1995 and May 1998 , 350 patients were enrolled at a single center-175 in the D and 175 in the T groups . All patients were followed until May 1998 , with a mean follow-up of 33.8+/-9.1 months . Using an intention-to-treat analysis , the 1- , 2- , 3- , and 4-year patient survival was 85.1 % , 81.6 % , 78.6 % , and 75.8 % , respectively , for D and 87.4 % , 85.4 % , 81.3 % , and 79.9 % , respectively , for T. The 4-year graft survival was 70 % for D and 72.1 % for T. Although the rate of acute rejection in the first 3 months was significantly lower for T than for D ( 28 % for triple vs. 38.9 % for double , P=0.03 ) , the overall rate of rejection for T at the end of 1 year was not significantly lower than for the D ( 38.9 % triple vs. 45.2 % double ) . The median time to the first episode of rejection was 14 days for D versus 24 days for T ( P=0.008 ) . During the study period , 38 of 175 patients in D received MMF to control ongoing acute rejection , nephrotoxicity , and /or neurotoxicity . On the other h and , 103 patients in the T discontinued MMF for infection , myelosuppression , and /or gastrointestinal disturbances . The need for corticosteroids was less after 6 months for T and the perioperative need for dialysis was lower with use of MMF . CONCLUSION This final report confirms similar patient survival and graft survival up to 4 years with a trend towards fewer episodes of rejection , lower need for steroids , and better perioperative renal function . However , the complex nature of LTx patients and their posttransplantation course prevents the routine application of MMF BACKGROUND Corticosteroids have long been a cornerstone of orthotopic liver transplant ( OLTx ) immunosuppression . Newer , more potent , agents have successfully allowed for more rapid tapering and discontinuation of corticosteroids in OLTx recipients . We hypothesize that corticosteroids can be safely avoided after the first postoperative day ( POD ) using these newer agents . METHODS Thirty adult OLTx recipients were prospect ively enrolled in a r and omized open-label , institutional review board-approved protocol . Fifteen patients ( group A ) received our st and ard regimen of tacrolimus , mycophenolate mofetil , and corticosteroids , and 15 patients ( group B ) received daclizumab , 2 mg/kg on POD 0 and 14 , with tacrolimus , mycophenolate mofetil , and corticosteroids on POD 0 and 1 and then discontinuation . In both groups , mycophenolate mofetil was tapered off between 3 and 4 months after OLTx . Bone mineral densitometry was performed at 1 , 3 , and 6 months after OLTx . Quantitative hepatitis C virus ( HCV ) polymerase chain reaction was obtained at days 0 , 7 , 14 , 21 , and 28 . Retransplant recipients , patients with autoimmune hepatitis , or status 1 or 2A patients were excluded . RESULTS Patient and graft survival rates were 93 % ( group A ) and 100 % ( group B ) with mean follow-up of 18 months . Patients in group B had more rejection diagnosed ( 25 % ) compared with group A ( 6.7 % ) . Yet , the incidence of biopsy-proven acute rejection requiring steroid therapy was 6.7 % in both groups . Hispanic race was common in groups A and B ( 87 % and 74 % ) . A total of six biopsies were performed in group B , with three patients having mild rejection responding to an increase in tacrolimus without the need for corticosteroids . One patient in group B was switched to cyclosporine for severe neurotoxicity and remains on monotherapy with normal graft function . No patient in either group developed a requirement for additional antihypertensive medication . Likewise , there were no patients with new-onset diabetes . The bone mineral densitometry was higher in group B at every time point but did not reach statistical significance . Serum cholesterol level was significantly ( P=0.03 ) lower in group B at 6 months after OLTx . Serum triglycerides were also lower , but the difference was not significant . Quantitative polymerase chain reaction for HCV-positive patients ( group A , n=7 ; group B , n=8 ) frequently increased after OLTx . There was no correlative decrease associated with daclizumab . At present , two patients in group A have documented HCV recurrence . CONCLUSION Corticosteroids can be safely avoided after POD 1 with the current regimen . With early follow-up , there is no difference in hypertension or diabetes or bone density . Lipid panels tended to be lower in patients who were not on corticosteroids . Longer term follow-up will be needed to demonstrate the potential advantage of corticosteroid avoidance in regard to hypertension , diabetes , and possibly HCV recurrence Posttransplant immunosuppression with calcineurin inhibitors ( CNIs ) is associated with impaired renal function , while mTor inhibitors such as everolimus may provide a renal‐sparing alternative . In this r and omized 1‐year study in patients with liver transplantation ( LTx ) , we sought to assess the effects of everolimus on glomerular filtration rate ( GFR ) after conversion from CNIs compared to continued CNI treatment . Eligible study patients received basiliximab induction , CNI with/without corticosteroids for 4 weeks post‐LTx , and were then r and omized ( if GFR > 50 mL/min ) to continued CNIs ( N = 102 ) or subsequent conversion to EVR ( N = 101 ) . Mean calculated GFR 11 months postr and omization ( ITT population ) revealed no significant difference between treatments using the Cockcroft‐Gault formula ( −2.9 mL/min in favor of EVR , 95%‐CI : [ −10.659 ; 4.814 ] , p = 0.46 ) , whereas use of the MDRD formula showed superiority for EVR ( −7.8 mL/min , 95%‐CI : [ −14.366 ; −1.191 ] , p = 0.021 ) . Rates of mortality ( EVR : 4.2 % vs. CNI : 4.1 % ) , biopsy‐proven acute rejection ( 17.7 % vs. 15.3 % ) , and efficacy failure ( 20.8 % vs. 20.4 % ) were similar . Infections , leukocytopenia , hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group . No hepatic artery thrombosis and no excess of wound healing impairment were noted . Conversion from CNI‐based to EVR‐based immunosuppression proved to be a safe alternative post‐LTx that deserves further investigation in terms of nephroprotection Less potent immunosuppression is considered to reduce the severity of hepatitis C virus ( HCV ) recurrence after liver transplantation . An optimal regimen is unknown . We evaluated tacrolimus monotherapy versus triple therapy in a r and omized trial of 103 first transplants for HCV cirrhosis . One hundred three patients who underwent transplantation for HCV were r and omized to tacrolimus monotherapy ( n = 54 ) or triple therapy with tacrolimus , azathioprine , and steroids ( n = 49 ) , which were tapered to zero by 3 to 6 months . Both groups had serial transjugular biopsies with hepatic venous pressure gradient ( HVPG ) measurement . The time to reach Ishak stage 4 was the predetermined endpoint . All factors documented in the literature as being associated with HCV recurrence and the allocated treatment were evaluated for reaching stage 4 and HVPG > or= 10 mm Hg . No significant preoperative , perioperative , or postoperative differences , including the frequency of biopsies between groups , were found . During a mean follow-up of 53.5 months , 9 monotherapy patients and 6 triple therapy patients died , and 5 monotherapy patients and 4 triple therapy patients underwent retransplantation . Stage 4 fibrosis was reached in 17 monotherapy patients and 10 triple therapy patients ( P = 0.04 ) , with slower fibrosis progression in the triple therapy patients ( P = 0.048 ) . Allocated therapy and histological acute hepatitis were independently associated with stage 4 fibrosis . HVPG increased to > or=10 mm Hg more rapidly in monotherapy patients versus triple therapy patients ( P = 0.038 ) . In conclusion , long-term maintenance immunosuppression with azathioprine and shorter term prednisolone with tacrolimus in HCV cirrhosis recipients result ed in a slower onset of histologically proven severe fibrosis and portal hypertension in comparison with tacrolimus alone , and this was independent of known factors affecting fibrosis A prospect i ve trial was conducted in 129 recipients of primary liver transplantation , to compare induction immunosuppression using triple drug therapy ( cyclosporine , steroids , and azathioprine ; group 1 , n = 42 ) , versus triple drug therapy with a 10-day course of OKT3 ( group 2 , n = 44 ) or of the anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 ( group 3 , n = 43 ) . Two-year actual patient survival rates were 64 % , 79 % , and 93 % in groups 1 , 2 , and 3 , respectively ( 1 vs. 2 , NS ; I vs. III , P = 0.003 ; 2 vs. 3 , NS ) . Up to 2 years after transplantation , 18 % , 44 % , and 53 % of the grafts in groups 1 , 2 , and 3 , respectively , had not experienced steroid-resistant acute rejection ( 1 vs. 2 , P = 0.002 ; 1 vs. 3 , P = 0.007 ; 2 vs. 3 , NS ) . The overall incidence of chronic rejection was 4 % . OKT3 therapy , but not LO-Tact-1 , significantly increased the incidence of cytomegalovirus infections ( P = 0.019 ) . In conclusion , immunoprophylaxis with LO-Tact-1 seemed to provide a liver graft acceptance rate at least as satisfactory as that with OKT3 , without an increase in the incidence of infections BACKGROUND / AIMS Acute rejection is still a major problem after liver transplantation . Ursodeoxycholic acid has beneficial effects in cholestasis by reducing the expression of major histocompatibility complex antigens . METHODS We have performed a double-blind r and omised study comparing ursodeoxycholic acid with placebo for the prevention of acute cellular rejection after liver transplantation . Twenty-six patients received ursodeoxycholic acid 600 mg per day and 24 patients received placebo for 2 months . RESULTS Neither rejection incidence nor rejection severity was significantly different in the two groups ( p > 0.90 ) . CONCLUSIONS We conclude that adjuvant ursodeoxycholic acid administration does not prevent rejection after liver transplantation We report the long-term follow-up ( > 1 year ) of 46 patients ( 12 pediatric ) r and omized to receive OKT3 for the first 14 days after OLT with low-dose steroids compared with 39 patients ( 8 pediatric ) who received cyclosporine , steroids , and azathioprine . The mean period of follow-up for survivors was 648±261 days for the OKT3 group and 682±216 days for the cyclosporine group . Of the OKT3 patients , 46 % were rejection-free in the first month compared with 31 % of CsA-treated patients ( P = NS ) . Rejection occurred after 1 month in 21 % of the OKT3 group patients compared with 19 % of the CsA group patients . One patient in each group developed vanishing bile duct syndrome . Eight patients in the OKT3 group and 13 in the CsA group experienced steroid-resistant rejection and required OKT3 rescue . In the 8 patients in whom OKT3 was reused , 4 had a positive ELISA after prophylaxis , and in 6 , CD3-positive cells were greater than 10 % during OKT3 reuse . Five patients resolved the episode . Of patients receiving OKT3 prophylaxis , 39 % developed anti-OKT3 antibodies . In the OKT3 group 83 % of patients and in the CsA group 75 % currently have normal liver function . There was no difference in serum creatinine for either adult or pediatric recipients at 12 months in the two groups . Eight episodes ( 2 CMV ) of severe infection occurred after 1 month in the OKT3 group compared to 11 ( 4 CMV ) in the CsA group . Graft survival , 63 % for the OKT3 group and 73 % for the CsA group , and patient survival , 67 % for the OKT3 group and 84 % for the CsA group , were not significantly different in the two groups . We recommend reserving the use of OKT3 for resistant rejection or when cyclosporine is contraindicated , as we can show no long-term benefit from its routine prophylactic use BACKGROUND The success of liver transplantation in this decade has become the stimulus to extend the donor and recipient pool . Reducing early posttransplant morbidity to maintain our success , as we exp and our frontiers , has led us to focus on balanced testing of multidrug immunosuppression regimens . METHODS A prospect i ve trial in orthotopic liver transplantation using Mycophenolate Mofetil and an identical steroid taper with r and omization of patients to Neoral ( N ) or Tacrolimus ( FK ) is the basis of this report . This was an intent-to-treat study design ed to compare the 6-month primary endpoints of rejection and infection and to compare the 6-month secondary endpoints of liver function , renal function , bone marrow function , hypertension , and serum cholesterol levels . RESULTS Ninety-seven patients completed the 6-month follow-up period ( N=49 , FK=48 ) . The actual 6-month patient and graft survival rates were 98 % and 94 % , respectively . There was no difference in the number of patients with rejection episodes ( N=11 , FK=8 ) ( P=0.61 ) . There were 24 infections ( 3 cytomegalovirus ) in the FK group and 30 infections ( 9 cytomegalovirus ) in the N group . The cholesterol levels at 6 months were not significantly different ( P=0.07 ) between the groups . The other secondary 6-month endpoints were not significantly different , except total bilirubin , which was lower in the FK arm ( P=0.02 ) . CONCLUSIONS The use of Mycophenolate Mofetil with N or FK and an identical steroid taper after orthotopic liver transplantation is associated with excellent graft and patient survival , and at 6 months , only 191 % of the patients experienced rejection , with a 48 % overall infection rate Renal impairment is common in patients after liver transplantation and is attributable in large part to the use of calcineurin inhibitor (CNI)-based immunosuppression . We sought to determine whether conversion to sirolimus-based immunosuppression was associated with improved renal function . In a single-center , r and omized , controlled trial , 30 patients at least 6 months post liver transplantation were r and omized to remain on CNI-based immunosuppression or to switch to sirolimus-based immunosuppression . The primary outcome measure was change in measured glomerular filtration rate ( GFR ) between baseline and 12 months . Of 30 patients r and omized , 3 were withdrawn at r and omization , leaving 14 patients on CNI and 13 on sirolimus . There was a significant improvement in delta GFR following conversion to sirolimus at 3 months ( 7.7 mL/minute/1.73 m2 ; 95 % confidence interval , 3.5 - 11.9 ) and 1 yr ( 6.1 mL/minute/1.73 m2 ; 95 % confidence interval , 0.9 - 11.4 ) . The difference in absolute GFR between the 2 study groups was significant at 3 months ( P=0.02 ) , but not at 12 months ( P=0.07 ) . The principal adverse events following conversion were the development of skin rash ( 9 of 13 patients , 69 % ) and mouth ulcers ( 5 of 13 patients , 38 % ) . Two patients developed acute rejection at 2 and 3 months following conversion , 1 in association with low sirolimus levels and 1 having stopped the drug inadvertently . In conclusion , overall , this study suggests that conversion to sirolimus immunosuppression is associated with a modest improvement in renal function . Side effects were common , but tolerable in most patients and controlled with dose reduction The purpose of this study was to evaluate the influence of a steroid-free immunosuppression on hepatitis C virus ( HCV ) recurrence . A total of 198 liver transplantation ( LT ) patients were r and omized to receive immunosuppression with basiliximab and cyclosporine , either with prednisone ( steroid [ St ] group ) or without prednisone ( no steroids [ NoSt ] group ) . The group of 89 HCV-infected patients was followed up with protocol biopsies for 2 years after LT . This group of HCV patients are the patients evaluated in the present study . The rejection rate was 19 % ( St : 21 % versus NoSt : 17 % ; P = 0.67 ) . Patients in the St group had a slightly higher rate of bacterial infections ( 59 % versus 38 % ; P = 0.05 ) . Almost all patients had histological HCV-recurrence ( St : 39/40 ( 97 % ) versus NoSt : 40/41 ( 97 % ) ; P = 1 ) . The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months , 1 year , and 2 years were , 23 % , 49 % , and 49 % in the NoSt group , compared to 33 % , 55 % , and 69 % in the St group , respectively ( P = 0.04 at 2 years ) . The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months , 1 year , and 2 years were 0 % , 8 % , and 22 % in the NoSt group , compared to 8 % , 19 % , and 31 % in the St group , respectively . Immunosuppression without steroids in HCV patients is safe , reduces bacterial infections and metabolic complications , and improves histological short-term evolution of HCV recurrence THE USE of cyclosporine ( CyA ) has greatly impacted the success of liver transplantation . FK 506 is a newly described immunosuppressive agent , with mechanisms of action similar to those of CyA , but more potent on a weight-to-weight basis . Pilot studies of FK 506 in primary liver transplantation have shown encouraging results .1 A r and omized trial using FK 506 with low-dose steroids ( LDS ) was compared to two different CyA regimens , one with LDS and the other with st and ard steroid therapy ( SST ) . The primary end point was to examine the incidence of rejection following liver transplantation , and to compare graft and patient survival rates after FK 506 with LDS , CyA with LDS , and CyA with SST The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Data from the 24‐month r and omized , multicenter , open‐label H2304 study in 719 de novo liver transplant recipients were analyzed to evaluate the influence of variables potentially affecting immunological or renal response : recipient age , gender , end‐stage disease , hepatitis C virus ( HCV ) status , and Model for End‐stage Liver Disease score and estimated glomerular filtration rate ( eGFR ) at r and omization ( day 30 ) . Treated BPAR was similar between everolimus with reduced tacrolimus ( EVR + Reduced TAC ) vs. conventional tacrolimus‐based therapy ( TAC Control ) in all sub population s , with a trend to lower risk under everolimus with reduced tacrolimus ( EVR + Reduced TAC ) in patients < 60 yrs and HCV‐negative recipients . Risk of graft loss or death was similar in both treatment groups for all sub population s. The change in eGFR to month 24 showed a benefit for EVR + Reduced TAC vs. TAC Control in all sub population s other than those with the lowest baseline eGFR ( 30 to < 55 mL/min/1.73m2 ) , with a significant difference in favor of EVR + Reduced TAC for younger recipients ( < 60 yr ) , female patients , HCV‐negative patients and those with baseline eGFR of 55 to < 70 mL/min/1.73 m2 . Everolimus with reduced tacrolimus maintains efficacy to at least two yr after liver transplantation even in patients with risk factors for rejection , with particular renal benefits in specific patient sub population Maintenance of adequate immunosuppression and avoidance of side‐effects are the goals of long‐term management of all organ‐transplanted patients . We here report the final results of a prospect i ve , r and omized trial comparing early cyclosporine monotherapy versus double‐drug therapy ( cyclosporine and steroids ) in adult liver transplantation patients . One hundred four patients were r and omized 3 months after transplantation either to continue ( Group I = 50 patients ) or to stop steroids ( Group II = 54 patients ) . Patients on a double‐drug regimen were maintained long term on methylprednisolone at a dose of 0.1 mg/kg/d . Target cyclosporine trough levels were between 150 and 250 ng/mL in both groups . Our main points of interest were the prevalence of acute and chronic rejections and steroid‐related side‐effects in the two groups of patients . Mean follow‐up was 41 ± 16 months ( range , 4‐68 months ) . Patient actuarial survival 2 and 5 years after r and omization was similar in the two groups ( 82 % vs. 83 % and 82 % vs. 77 % ) . The prevalence of acute rejections after r and omization was , respectively , 8 % and 4 % . A single episode of chronic rejection was observed only in a patient on long‐term steroid therapy . Side‐effects of steroid therapy were less frequent in patients weaned off steroids , and when considering hypertension and diabetes , the differences between the two groups were statistically significant . Early cyclosporine monotherapy is a safe undertaking in liver transplantation because it allows a significant reduction of steroid‐related side‐effects without increasing the risk of acute and chronic rejection . After 5 years , patient survival was similar in patients with or without steroids Calcineurin inhibitors ( CNIs ) contribute to renal dysfunction following liver transplantation . This prospect i ve , r and omized , multicenter , 6-month study ( with an additional 6 months of follow-up ) evaluated whether everolimus with CNI reduction or discontinuation would improve renal function in maintenance liver transplant recipients experiencing CNI-related renal impairment . Patients started everolimus therapy with CNI reduction or discontinuation ( n = 72 ) or continued receiving st and ard-exposure CNI ( n = 73 ) . At month 6 , 80 % of the patients who had converted to everolimus had discontinued the CNI . The mean change in creatinine clearance ( CrCl ) from baseline to month 6 was similar between groups ( everolimus , 1.0 + /- 10.2 mL/minute ; controls , 2.3 + /- 7.8 mL/minute ; P = 0.46 ) , so the primary study endpoint ( 8 mL/minute difference in the change in CrCl ) was not achieved . Among patients who continued everolimus according to the protocol , the mean increase in CrCl was 2.1 ( n = 53 ) and 3.8 mL/minute ( n = 38 ) at months 6 and 12 , respectively , versus 2.4 ( n = 68 ) and 3.5 mL/minute in controls ( n = 51 ) . The high frequency of CNI dose reductions in controls ( 77 % of the patients ) and the relatively long mean time post-transplant ( > 3 years ) likely contributed to the small difference in CrCl . Biopsy-proven acute rejection occurred in 1.4 % of the patients in each group , with no graft losses . Study drug discontinuation was higher in everolimus-treated patients , and adverse events were more frequent . These data demonstrate that everolimus allows for discontinuation or a major reduction of CNI exposure in liver allograft recipients suffering CNI-related renal dysfunction without a loss of efficacy . Trials targeting earlier conversion post-transplantation are required to confirm the efficacy and safety of everolimus for improving renal function after liver transplantation The purpose of this prospect i ve , r and omized , multicenter trial was to evaluate the effects of a steroid-avoiding immunosuppression protocol on hepatitis C virus (HCV)-positive recipients of living donor liver transplantation ( LDLT ) . Seventy-five HCV-positive LDLT recipients were included in this study , and they were r and omized to receive tacrolimus ( TAC ) plus a corticosteroid ( ST ; n = 35 ) or TAC plus mycophenolate mofetil ( MMF ; n = 40 ) . Biopsy-proven acute rejection ( BPAR ) was treated with steroid pulse therapy in both groups . Protocol biopsy was performed 3 , 6 , and 12 months after LDLT and annually thereafter . Histological recurrence of HCV ( fibrosis stage ≥ F1 according to the METAVIR score ) , BPAR resistant to 2 sets of steroid pulse therapy , hepatocellular carcinoma ( HCC ) recurrence , retransplantation , and patient death were defined as events , and the primary endpoint was event-free survival . The median follow-up was 55 months . The event-free survival rates at 1 , 3 , and 5 years were 38.2 % , 11.8 % , and 5.9 % , respectively , for the ST group and 25.0 % , 17.5 % , and 14.6 % , respectively , for the MMF group ( P = 0.45 ) . The overall 5-year patient survival rates were similar for the ST group ( 82.7 % ) and the MMF group ( 81.0 % , P = 0.28 ) . Steroid-resistant BPAR occurred in only 1 patient from the MMF group . HCC recurrence occurred for 1 patient from the ST group and 2 patients from the MMF group . HCV recurrence rates with a fibrosis stage ≥ F1 1 and 3 years after LDLT were 59.4 % and 85.9 % , respectively , for the ST group and 74.2 % and 81.9 % , respectively , for the MMF group ( P = 0.57 ) . In conclusion , our steroid-avoidance regimen had no apparent impact on LDLT outcomes for HCV-positive recipients Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
10,359 | 18,460,944 | This effect is expressed by worse in-vitro fertilization parameters in cycles performed on women with smoking habits .
Also , uterine receptiveness is significantly altered by the smoking habit .
In men , cigarette smoking reduces sperm production , increases oxidative stress , and DNA damage .
Spermatozoa from smokers have reduced fertilizing capacity , and embryos display lower implantation rates .
Even in-utero exposition to tobacco constituents leads to reduced sperm count in adult life .
SUMMARY A strong body of evidence indicates that the negative effect of cigarette smoking on fertility comprises fairly every system involved in the reproductive process . | PURPOSE OF REVIEW To perform a systematic review of the literature on the relationship between cigarette smoking and reproductive function .
RECENT FINDINGS Tobacco compounds exert a deleterious effect on the process of ovarian follicle maturation . | OBJECTIVE To evaluate whether baseline or procedural stress during in vitro fertilization ( IVF ) or gamete intrafallopian transfer ( GIFT ) affects pregnancy or live birth delivery rates . DESIGN Prospect i ve study . SETTING Seven clinics in Southern California between 1993 and 1998 . PATIENT(S ) One hundred and fifty-one women completed two question naires . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) The number of oocytes aspirated and fertilized , the number of embryos transferred , the achievement of a pregnancy , live birth delivery , and infant outcomes . RESULT ( S ) Positive-affect negative-affect score at baseline negatively influenced the number of oocytes retrieved and embryos transferred . A higher expectation of pregnancy was associated with greater numbers of oocytes fertilized and embryos transferred . At baseline , the risk of no live birth was 93 % lower for women who had the highest positive-affect score compared to those with the lowest score . Furthermore , the score on the Infertility Reaction Scale was related to negative outcomes in live birth delivery , infant birth weight , and multiple births . During the time of the procedure , the PANAS and Bipolar Profile of Moods States results were related to the number of oocytes fertilized and embryos transferred ; stress did not affect pregnancy or delivery . CONCLUSION ( S ) Baseline ( acute and chronic ) stress affected biologic end points ( i.e. , number of oocytes retrieved and fertilized ) , as well as pregnancy , live birth delivery , birth weight , and multiple gestations , whereas ( procedural ) stress only influenced biologic end points In a case-control study an association was found between mothers ' smoking habits and the frequency of dizygotic twinning . As cases were included all twins born in Denmark in 1984 and 1985 . A r and om sample of 1.5 % of mothers to singletons , born in the same period were selected as controls . Only live-borns , conceived after no hormonal treatment , were included in the study . The finding may be due to the well-known anti-estrogen effect of smoking In the present study we investigated the effect of a woman 's smoking status on the quality of the oocyte , zygote , and on day 3 pre-embryo , as well as the likelihood of achieving an ongoing pregnancy at 8 weeks . Smokers presented a higher number of nonfertilized oocytes than nonsmokers ( 20.1 % vs. 10.8 % of fertilization failure ) , by comparable clinical pregnancy rate for smokers ( 40.8 % ; 28/72 ) and for nonsmokers ( 39.2 % ; 23/58 ) We investigated whether cigarette smoking , measured by follicular fluid concentrations of cotinine ( a major metabolite of nicotine ) , affects the maturity of oocytes from women undergoing in-vitro fertilization ( IVF ) and embryo transfer . In 234 women , follicular fluid sample s were assessed for cotinine and their 2020 oocytes were assessed for maturity stage . Data on individual proportions of oocytes which were mature ( OM ) and were fertilized ( OF ) were analysed by regression in relation to age and follicular fluid cotinine . OF gave an independent assessment of oocyte maturity . Both age and follicular fluid cotinine entered the OM and OF regressions and were significant . The age-adjusted regression coefficients for log cotinine were positive ; greater cotinine concentrations usually accompanied greater OM and OF . The cotinine effect on OM was positive in younger women , but it became negative ( decreased OM with increasing cotinine concentrations ) in older women ( > or = 40 years ) . We further found in older women an average reduction of approximately 50 % in the number of mature oocytes ; this reduced number was lower than the number of embryos usually transferred . Smoking can reduce the number of mature oocytes even further , therefore risking a negative IVF-embryo transfer outcome . This may be the reason why the negative effects of smoking become clinical ly detectable in older women OBJECTIVE This study determines whether smoking influences ovarian vascularization which thus may impair follicular development . DESIGN Prospect i ve laboratory study of follicular fluids and granulosa cells from patients undergoing in vitro fertilization . SETTING University Hospital Aachen , Germany . PATIENT(S ) Fifty smoking women and 50 nonsmoking women . INTERVENTION(S ) Cultivation of human granulosa cells . Cultivation of human umbilical vein endothelial cells ( HUVECs ) with either granulosa cell-conditioned medium or follicular fluid . Determination of clinical parameters . MAIN OUTCOME MEASURE(S ) Quantification of soluble vascular endothelial growth factor receptor 1 ( sVEGFR-1 ) and cotinine . RESULT ( S ) Mean sVEGFR-1 concentration in follicular fluid of smokers was 499.6 pg/mL compared with 159.2 pg/mL in nonsmokers . Correspondingly , supernatant of HUVECs cultured with follicular fluid from smoking and nonsmoking women showed , respectively , 1,174.1 pg/mL versus 794.2 pg/mL sVEGFR-1 . The HUVECs incubated with conditioned medium from smokers ' granulosa cells at culturing days 5 , 9 , 13 , and 17 secreted , respectively , 1,712.4 , 1,560.6 , 1,619.0 , and 1,635.0 pg/mL sVEGFR-1 , whereas nonsmokers showed , respectively , 1,147.6 , 1,067.2 , 1,135.9 , and 1,206.3 pg/mL sVEGFR-1 . Mean cotinine concentration in smoking women was 83.9 ng/mL and in nonsmoking was 2.8 ng/mL. In all four comparisons , differences between groups reached statistical significance . CONCLUSION ( S ) This study showed that smokers secrete significantly higher amounts of sVEGFR-1 than nonsmokers , which may result in decreased ovarian vascularization and reduced oocyte maturation A prospect i ve cohort study of 222 consecutive couples undergoing 297 cycles of in-vitro fertilization and embryo transfer ( IVF-ET ) was conducted to evaluate the impact of cigarette smoking in males and females . Compared with non-smokers , females smoking at the time of treatment had more previous pregnancies ( 1.16 versus 0.63 , P less than 0.001 ) , consumed more coffee per day ( 3.29 versus 1.85 cups , P = 0.001 ) and were less likely to hold a professional or skilled job ( 41 % versus 66 % ) . There was no difference in the response to ovarian stimulation in terms of the duration and dose of human menopausal gonadotrophin , peak oestradiol level or number of oocytes retrieved . The fertilization rate was actually higher in heavy smokers than in non-smokers ( 79.3 % versus 61.3 % , P = 0.007 ) . The rate of embryo cleavage was retarded in a dose-dependent fashion . In smokers of 1 - 14 cigarettes/day , the likelihood of transferring an embryo at greater than or equal to 4-cell stage was 0.87 [ 95 % confidence limits ( CL ) 0.56 - 1.4 ] and in smokers of greater than or equal to 15 cigarettes/day , the likelihood was 0.52 ( 95 % CL 0.31 - 0.88 ) . However , evaluation of interrelated factors using logistic regression suggested that a low socioeconomic status had a greater detrimental effect on embryo cleavage rate than female smoking . No significant difference was noted in the clinical outcome following embryo transfer . A study of larger sample size is required to evaluate whether the effects of cigarette smoking are independent of socioeconomic status and other related factors and whether they result in reduced ongoing clinical pregnancy and live birth rates The aim of the present study was to evaluate consequences of cigarette smoking on male gametes . In this prospect i ve study , sperm parameters such as sperm density , motility , viability and normal morphology were measured according to the WHO criteria . In addition to these st and ard parameters , we analysed the degree of DNA fragmentation in spermatozoa using the TUNEL-assay with flow cytometry detection in 57 non-smokers and 51 smokers seeking for infertility counselling . The smoking intoxication was assessed by question naire and measured with the CO-Tester . We show that smokers ' spermatozoa have a significantly higher DNA fragmentation than non-smokers ( 32 % versus 25.9 % , p<0.01 ) . In contrast there is no significant difference in conventional parameters between smokers and non-smokers . The degree of sperm DNA fragmentation is not significantly correlated with any of the conventional parameters . These findings suggest that cigarette smoking may have deleterious effects on sperm nuclear quality and that sperm DNA fragmentation can therefore be considered as an independent parameter with diagnostic , prognostic , and strategic value in the treatment of infertility Purpose : The aim of the present study was to investigate the influence of smoking on different parameters such as oocyte count , embryo score , and basal hormone values within the scope of in vitro fertilization – embryo transfer ( IVF-ET ) . Methods : Eight hundred thirty-four women undergoing IVF-ET treatment were classified as smokers or nonsmokers on the basis of question naires . Additionally , we divided them into three groups according to their stimulation protocol —“combined stimulation ” [ I ; clomiphene citrate plus human menopausal gonadotropin ( hMG ) ] , “ ultrashort ” [ II ; gonadotropin releasing hormone agonist ( GnRHa ) plus hMG or follicle-stimulating hormone ( FSH ) ] , and “ long downregulation protocol ” (III)— and further classified again as smokers or nonsmokers within the groups . Results : In general , smoking patients were significantly ( P = 0.0195 ) younger than nonsmokers and showed a significantly ( P = 0.0379 ) lower embryo score and a tendency ( P = 0.0931 ) to produce fewer oocytes . There was no significant difference concerning the number of normally or pathologically fertilized and transfered oocytes and embryos suitable for cryopreservation . Women who smoked had significantly ( P = 0.0112 ) higher basal 17-β-estradiol ( E2 ) , luteinizing hormone ( LH ) ( P = 0.0001 ) , and dehydroepi and rosteronesulfate ( DHEAS ) ( P = 0.0039 ) levels , but their basal human prolactin ( HPRL ) levels were significantly ( P = 0.0033 ) lower than those of nonsmokers . According to the stimulation protocol used , we found the following results . Smoking patients in group I showed a significantly ( P = 0.023 ) lower embryo score and produced fewer oocytes ( P = 0.0113 ) , with fewer of them being fertilized ( P = 0.0072 ) and transferred ( P = 0.0067 ) . Women who smoked had significantly ( P = 0.0002 ) higher basal LH levels , but their HPRL levels were significantly ( P = 0.031 ) lower than those of nonsmokers . Furthermore , they had a thinner endometrium on the day of embryo transfer ( P = 0.0366 ) . In group II we measured significantly elevated basal E2levels ( P = 0.0089 ) and higher LH values ( P = 0.0092 ) in smokers . Group III showed a trend ( P = 0.0565 ) toward lower HPRL values in smokers . Conclusions : Although the fertilization rate of oocytes and the pregnancy rate were not significantly different between smokers and nonsmokers , we found significantly alterated hormonal parameters and negatively influenced oocyte parameters , particularly after clomiphene stimulation . So we might consider using only GnRHa protocol s for smoking patients . Additionally , we advise our patients to stop smoking before an IVF-ET treatment because of the complex effects of smoking on the reproductive and hormonal system BACKGROUND No information exists in the literature regarding the factors affecting the blood flow towards the endometrial and subendometrial regions during IVF treatment . METHODS We examined the effect of women 's age , their smoking habits , their type of infertility ( i.e. primary or secondary ) and parity , causes of infertility and serum estradiol ( E2 ) concentration on endometrial and subendometrial blood flows as measured by a three-dimensional ( 3D ) power Doppler ultrasound during IVF treatment . All patients received a st and ard long protocol of ovarian stimulation and serum E2 concentration was determined on the day of hCG . 3D ultrasound examination with power Doppler was performed on the day of oocyte collection to determine vascularization index ( VI ) , flow index ( FI ) and vascularization flow index ( VFI ) of endometrial and subendometrial regions . RESULTS The age of women , their smoking habits , their types of infertility and parity and causes of infertility had no effect on the endometrial and subendometrial 3D power Doppler flow indices . There was a negative correlation between serum E(2 ) concentration and endometrial FI ( r = -0.109 ; P = 0.006 ) . CONCLUSIONS Endometrial blood flow in IVF treatment was negatively affected by serum E2 concentration only OBJECTIVE To determine whether moderate cigarette smoking and alcohol consumption in teenage men is associated with increases in disomic sperm and detectable changes in semen quality . DESIGN Cohort study . SETTING Military recruiting station , Teplice , Czech Republic . PATIENT(S ) Ten current smokers ( 20 cigarettes per day for at least 2 years , exposure confirmed by urine cotinine ) who also consumed alcohol and 15 nonsmokers . All patients were exactly 18 years old , healthy , and of unproven fertility . MAIN OUTCOME MEASURE(S ) Sperm aneuploidy by multicolor fluorescence in situ hybridization for chromosomes 8 , X , and Y ; conventional semen analyses ; computer-aided sperm analysis for motility ; and sperm chromatin structure analysis . RESULTS Smokers showed elevated frequencies of sperm aneuploidy ( Y disomy , P < 0.001 ; aggregate of X , Y , and 8 disomies , P < 0.01 ) ; reduced linearity of sperm motion ( P < 0.05 ) ; and more " round-headed " sperm ( P < 0.01 ) . Smokers ' semen contained fewer sperm ( P < 0.001 ) and fewer motile sperm ( P < 0.02 ) , which was attributable , in part , to shorter abstinence intervals among smokers ( P < 0.02 ) . CONCLUSION ( S ) Cigarette smoking among teenagers was associated with increases in disomic sperm and a diminution in specific aspects of semen quality . Such defects may affect male fertility and may increase future chances of fathering offspring with aneuploidy syndromes |
10,360 | 23,823,142 | Overall , most interventions showed to objective ly improve cognitive performance in subjects with SCCs .
Conversely , there is a current lack of evidence in the literature about the efficacy of nonpharmacological cognitive interventions for preventing dementia or cognitive impairment | Subjective cognitive complaints ( SCCs ) are being increasingly recognized as a pre clinical phase of dementia .
Thus , SCCs may represent a “ promising ” stage for planning and implementing preventive interventions aim ed at reducing the incidence of cognitive disorders .
The aim of the present study is to present and discuss the available evidence coming from clinical trials adopting cognitive interventions in individuals with SCCs . | Abstract 1680 participants were r and omized over the recruitment period in MAPT study . A total of 1290 participants were recruited in the 7 University Hospital centers , and 390 participants in the 6 memory clinics around Toulouse Gerontopole / Alzheimer Disease research clinical center . The first r and omization was on May 30 , 2008 , and the targeted number of r and omized participants was reached on February 24 , 2011 ; 2595 subjects were finally screened , of which 1680 fulfilled the eligibility criteria which represents 64.8 % . Approximately , one quarter of screened people refused to participate after the detailed presentation of the study and 4.3 % were still interested in participating but missed for unknown reasons the baseline visit even after repeated contacts . Of the 1810 subjects who signed the consent for participating to the study at the baseline visit , 130 ( 7.1 % ) were excluded because one of the eligibility criteria was not satisfied . Interestingly , the higher percentage of r and omizations compared to screened participants is the personal contact source ; almost 85 % of screened participants entered in the study . In an equivalent way , Medias and conferences are efficient recruiting sources to enrol volunteers in the study . Unexpectedly , only about 60 % of screened participants from the hospital and GP sources were r and omized and 33.2 % from health care services . Almost a quarter of the r and omized participants come from the hospital out patients clinics and approximately 20 % from public conferences . A total of 1128 contacts yielded to 556 screened volunteers and 345 r and omized participants in the coordinating center of Toulouse . Thus , 30 % of contacts were recruited Objective : This study presents a new comprehensive educational group intervention that offers psycho-education about cognitive aging and context ual factors ( i.e. , negative age stereotypes , beliefs , health , and lifestyle ) , focuses on skills and compensatory behavior , and incorporates group discussion . Its effects were investigated in community-dwelling older women who report normal age-related cognitive complaints . Methods : A r and omized controlled trial with an experimental and waiting-list control condition was carried out in a sample of 50 women aged 60–75 years . As the main problem of these individuals were perceived cognitive deficits without actual cognitive decrements , metacognition served as the primary outcome measure . Objective cognitive functioning and psychological well-being were secondary outcome measures . A double baseline and a follow-up assessment were carried out . Results : Participants in the experimental condition reported significantly fewer negative emotional reactions toward cognitive functioning ( U = 164.500 , p = 0.004 ) . The reported effect size ( δ = −0.473 ) could be interpreted as large . Conclusions : This new comprehensive educational group intervention reduces negative emotional reactions toward cognitive functioning , which seems a prerequisite for improved subjective cognitive functioning and well-being . It can potentially contribute the well-being of an important and large group of older adults OBJECTIVE The objective of this study was to determine the effects of a 14-day healthy longevity lifestyle program on cognition and cerebral metabolism in people with mild age-related memory complaints . METHODS Seventeen nondemented subjects , aged 35 - 69 years ( mean : 53 years , st and ard deviation : 10 ) with mild self-reported memory complaints but normal baseline memory performance scores were r and omly assigned to 1 ) the intervention group ( N = 8) : a program combining a brain healthy diet plan , relaxation exercises , cardiovascular conditioning , and mental exercise ( brain teasers and verbal memory training techniques ) ; or 2 ) the control group ( N = 9 ) : usual lifestyle routine . Pre- and postintervention measures included self- assessment s of memory ability , objective tests of cognitive performance , and determinations of regional cerebral metabolism during mental rest with [fluorine-18]fluorodeoxyglucose ( FDG ) positron emission tomography ( PET ) . RESULTS Subjects in the intervention group objective ly demonstrated greater word fluency . Concomitantly , their FDG-PET scans identified a 5 % decrease in activity in the left dorsolateral prefrontal cortex . The control group showed no significant change in any of the measures . CONCLUSIONS A short-term healthy lifestyle program combining mental and physical exercise , stress reduction , and healthy diet was associated with significant effects on cognitive function and brain metabolism . Reduced resting activity in left dorsolateral prefrontal cortex may reflect greater cognitive efficiency of a brain region involved in working memory CONTEXT Cognitive function in older adults is related to independent living and need for care . However , few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently . OBJECTIVE To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older , independent-living adults . DESIGN R and omized , controlled , single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001 . SETTING AND PARTICIPANTS Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing , community centers , and hospital/clinics in 6 metropolitan areas in the United States . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : 10-session group training for memory ( verbal episodic memory ; n = 711 ) , or reasoning ( ability to solve problems that follow a serial pattern ; n = 705 ) , or speed of processing ( visual search and identification ; n = 712 ) ; or a no-contact control group ( n = 704 ) . For the 3 treatment groups , 4-session booster training was offered to a 60 % r and om sample 11 months later . MAIN OUTCOME MEASURES Cognitive function and cognitively dem and ing everyday functioning . RESULTS Thirty participants were incorrectly r and omized and were excluded from the analysis . Each intervention improved the targeted cognitive ability compared with baseline , durable to 2 years ( P<.001 for all ) . Eighty-seven percent of speed- , 74 % of reasoning- , and 26 % of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period . Booster training enhanced training gains in speed ( P<.001 ) and reasoning ( P<.001 ) interventions ( speed booster , 92 % ; no booster , 68 % ; reasoning booster , 72 % ; no booster , 49 % ) , which were maintained at 2-year follow-up ( P<.001 for both ) . No training effects on everyday functioning were detected at 2 years . CONCLUSIONS Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities . Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals . Because of minimal functional decline across all groups , longer follow-up is likely required to observe training effects on everyday function What is the neurocognitive basis for the considerable individual differences observed in functioning of the adult mind and brain late in life ? We review the evidence that in healthy old age the brain remains capable of both neuronal and cognitive plasticity , including in response to environmental and experiential factors . Neuronal plasticity ( e.g. , neurogenesis , synaptogenesis , cortical re-organization ) refers to neuron-level changes that can be stimulated by experience . Cognitive plasticity ( e.g. , increased dependence on executive function ) refers to adaptive changes in patterns of cognition related to brain activity . We hypothesize that successful cognitive aging requires interactions between these two forms of plasticity . Mechanisms of neural plasticity underpin cognitive plasticity and in turn , neural plasticity is stimulated by cognitive plasticity . We examine support for this hypothesis by considering evidence that neural plasticity is stimulated by learning and novelty and enhanced by both dietary manipulations ( low-fat , dietary restriction ) and aerobic exercise . We also examine evidence that cognitive plasticity is affected by education and training . This is a testable hypothesis which could be assessed in humans in r and omized trials comparing separate and combined effects of cognitive training , exercise , and diet on measures of cognitive and brain integrity . Greater underst and ing of the factors influencing the course of cognitive aging and of the mechanisms underlying those factors could provide information on which people could base choices that improve their ability to age successfully CONTEXT Frequent participation in cognitively stimulating activities has been hypothesized to reduce risk of Alzheimer disease ( AD ) , but prospect i ve data regarding an association are lacking . OBJECTIVE To test the hypothesis that frequent participation in cognitive activities is associated with a reduced risk of AD . DESIGN Longitudinal cohort study with baseline evaluations performed between January 1994 and July 2001 and mean follow-up of 4.5 years . PARTICIPANTS AND SETTING A total of 801 older Catholic nuns , priests , and brothers without dementia at enrollment , recruited from 40 groups across the United States . At baseline , they rated frequency of participation in common cognitive activities ( eg , reading a newspaper ) , from which a previously vali date d composite measure of cognitive activity frequency was derived . MAIN OUTCOME MEASURES Clinical diagnosis of AD by a board-certified neurologist using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer 's Disease and Related Disorders Association criteria and change in global and specific measures of cognitive function , compared by cognitive activity score at baseline . RESULTS Baseline scores on the composite measure of cognitive activity ranged from 1.57 to 4.71 ( mean , 3.57 ; SD , 0.55 ) , with higher scores indicating more frequent activity . During an average of 4.5 years of follow-up , 111 persons developed AD . In a proportional hazards model that controlled for age , sex , and education , a 1-point increase in cognitive activity score was associated with a 33 % reduction in risk of AD ( hazard ratio , 0.67 ; 95 % confidence interval , 0.49 - 0.92 ) . Results were comparable when persons with memory impairment at baseline were excluded and when terms for the apolipoprotein E epsilon4 allele and other medical conditions were added . In r and om-effects models that controlled for age , sex , education , and baseline level of cognitive function , a 1-point increase in cognitive activity was associated with reduced decline in global cognition ( by 47 % ) , working memory ( by 60 % ) , and perceptual speed ( by 30 % ) . CONCLUSION These results suggest that frequent participation in cognitively stimulating activities is associated with reduced risk of AD In an interdisciplinary project on maintaining and supporting independent living in old age , ( a ) competence training , ( b ) memory training and ( c ) psychomotor training as well as ( d ) combined competence and psychomotor training and ( e ) combined memory and psychomotor training was performed with n = 309 elderly of 75 to 89 years of age for 9 months . Regardless of treatment conditions , an age-related decline of health and subjective well-being was found 1 year after the end of the training . The specific training measures each led to highly significant specific improvements of the trained functions . A favorable influence of competence training on everyday coping and hence on active strategies for staying independent as well as of memory training on all cognitive functions and especially on memory performance was found . While global psychomotor performance was not significantly improved , effects of psychomotor training on specific functions were detected . In addition , the combined psychomotor and memory training led to an improvement of psychomotor performance and to a reduction of symptoms of dementia , even though neither psychomotor training alone nor memory training alone result ed in such effects . Neurophysiological changes leading to a provision of reserve-capacity of CNS-performance are among other effects assumed as an explanation The objective of the study was to examine the effectiveness of two types of memory training ( collective and individual ) , compared to control ( waiting list ) , on memory performance . Participants were 139 community-dwelling older individuals recruited through media advertisements asking for people with subjective memory complaints to participate in a study . Data were collected at baseline , and at 1 week and 4 months after the intervention . Training efficacy was assessed using measures of subjective and objective memory performance . After the intervention , participants in the collective training group reported more stability in memory functioning and had fewer feelings of anxiety and stress about memory functioning . In addition , positive effects were found on objective memory functioning . Compared with the other two groups , the collective training group participants had an improved recall of a previously learned word list . Compared to controls , participants in the individual training group reported fewer feelings of anxiety and stress in relation to memory functioning PURPOSE To compare the efficacy of cognitive training ( CT ) and cognitive stimulation ( CS ) programs for the community elderly with subjective memory complaints ( SMC ) . METHOD The single-blind non-r and omized controlled study was applied . The numbers of CT and CS participants were 14 and 11 . The mean ages of CT and CS participants were 68.71 and 70.36 . Memory training and problem solving strategies were applied in the CT group . There were ten 2-hourly sessions of CT , held twice weekly . CS group met once weekly in a 1.5-h class for eight classes . Cognitive performance tests of general cognitive performance , verbal memory and executive function were measured before/after the training and at 6 months follow-up . RESULTS In both training conditions , the general cognitive performance were enhanced . The CT group showed improvement in the verbal memory test . The CS group did not trigger any training effect in the verbal memory test but the executive function . All cognitive progresses remained at follow-up . CONCLUSION Both cognitive training and cognitive stimulation programs showed training effects and remained until 6 months CONTEXT Cognitive training has been shown to improve cognitive abilities in older adults but the effects of cognitive training on everyday function have not been demonstrated . OBJECTIVE To determine the effects of cognitive training on daily function and durability of training on cognitive abilities . DESIGN , SETTING , AND PARTICIPANTS Five-year follow-up of a r and omized controlled single-blind trial with 4 treatment groups . A volunteer sample of 2832 persons ( mean age , 73.6 years ; 26 % black ) , living independently in 6 US cities , was recruited from senior housing , community centers , and hospitals and clinics . The study was conducted between April 1998 and December 2004 . Five-year follow-up was completed in 67 % of the sample . INTERVENTIONS Ten-session training for memory ( verbal episodic memory ) , reasoning ( inductive reasoning ) , or speed of processing ( visual search and identification ) ; 4-session booster training at 11 and 35 months after training in a r and om sample of those who completed training . MAIN OUTCOME MEASURES Self-reported and performance-based measures of daily function and cognitive abilities . RESULTS The reasoning group reported significantly less difficulty in the instrumental activities of daily living ( IADL ) than the control group ( effect size , 0.29 ; 99 % confidence interval [ CI ] , 0.03 - 0.55 ) . Neither speed of processing training ( effect size , 0.26 ; 99 % CI , -0.002 to 0.51 ) nor memory training ( effect size , 0.20 ; 99 % CI , -0.06 to 0.46 ) had a significant effect on IADL . The booster training for the speed of processing group , but not for the other 2 groups , showed a significant effect on the performance-based functional measure of everyday speed of processing ( effect size , 0.30 ; 99 % CI , 0.08 - 0.52 ) . No booster effects were seen for any of the groups for everyday problem-solving or self-reported difficulty in IADL . Each intervention maintained effects on its specific targeted cognitive ability through 5 years ( memory : effect size , 0.23 [ 99 % CI , 0.11 - 0.35 ] ; reasoning : effect size , 0.26 [ 99 % CI , 0.17 - 0.35 ] ; speed of processing : effect size , 0.76 [ 99 % CI , 0.62 - 0.90 ] ) . Booster training produced additional improvement with the reasoning intervention for reasoning performance ( effect size , 0.28 ; 99 % CI , 0.12 - 0.43 ) and the speed of processing intervention for speed of processing performance ( effect size , 0.85 ; 99 % CI , 0.61 - 1.09 ) . CONCLUSIONS Reasoning training result ed in less functional decline in self-reported IADL . Compared with the control group , cognitive training result ed in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00298558 Community-dwelling , nondemented older people ( 60 - 70 years ) with reported memory complaints were r and omly assigned to either a memory-h and book ( MHB ) group ( n = 20 ) or a placebo group ( n = 20 ) . The MHB group members were given a self-contained memory h and book and were individually trained on two of the h and book 's sections that related to ( a ) remembering a person 's name and ( b ) prospect i ve memory , for approximately 30 minutes each . The placebo group was given an instructional pamphlet with a description of three list-learning mnemonics as a placebo treatment . Subjects were tested before and after the intervention . When compared with the placebo group , the MHB group members significantly improved their performance on a face-naming task and a strategies knowledge question naire , but not on the prospect i ve memory measures , when compared with the placebo group . In addition , the MHB group showed a significant advantage on an everyday memory diary that was filled out by all subjects following the intervention . Following the study , the placebo group was also given the memory h and book , and both groups were then assessed on their knowledge and use of strategies by question naire at a 4-month follow-up . At this time the MHB group appeared to maintain most of its original gains , while the placebo group made some improvement |
10,361 | 29,889,916 | The overall survival rate of single-tooth ceramic restorations fabricated with CAD/CAM technology was similar to those conventionally manufactured | Owing to an increased dem and for safe and esthetically pleasing dental material s , ceramics have been developed and optimized to rehabilitate anterior and posterior teeth .
This evolution in ceramic material s is directly related to the development of sophisticated processing technologies and systems for use in dental medicine , particularly computer-aided design /computer-assisted manufacture ( CAD/CAM ) technology .
This study is a systematic review outlining long-term clinical survival rates of single-tooth restorations fabricated with CAD/CAM technology with a minimum follow-up of 3 years . | PURPOSE The present follow-up study was carried out to evaluate the performance of Class II Cerec inlays after 10 years of clinical service . MATERIAL S AND METHODS Sixty-six Class II CAD/CAM ceramic inlays were placed in 27 patients . Each patient received at least one inlay luted with a dual-cured resin composite and one inlay luted with a chemically cured resin composite . At the 10-year recall , 25 ( 93 % ) patients with 61 ( 92 % ) inlays were available for evaluation using a slight modification of the USPHS criteria . RESULTS Fifty-four ( 89 % ) of the 61 inlays reevaluated still functioned well at the 10-year recall . During the follow-up period , seven ( 11 % ) of the inlays required replacement because of : four inlay fractures , one cusp fracture , endodontic problems in one case , and postoperative symptoms in one case . All the replaced inlays had been luted with the dual-cured resin composite . The fractured inlays were all placed in molars . The estimated survival rate after 10 years was 89 % , 77 % for the dual-cured resin composite-luted inlays and 100 % for the chemically cured resin composite-luted ones . The difference was statistically significant . CONCLUSION Patient satisfaction with and acceptance of the Cerec inlays were high , and the performance after 10 years of clinical service was acceptable , especially regarding the inlays luted with the chemically cured resin composite . The properties of the luting agents seem to affect the longevity of the type of ceramic inlays evaluated OBJECTIVES To evaluate fixed dental prostheses ( FDPs ) and single crowns made of zirconia substructures veneered with new fluorapatite veneering porcelain . METHOD AND MATERIAL S Thirty-eight patients received 18 FDPs and 50 single crowns . Zirconia substructures were fabricated by a CAD/CAM system and veneered using the powder buildup technique . All restorations were cemented with glass ionomer . Baseline evaluation was performed 2 weeks after cementation with recall examinations at 12 , 24 , and 36 months by calibrated investigators . SEM was performed on replicas of all restorations . Survival probabilities according to Kaplan-Meier were calculated . RESULTS The mean service time was 35 ( + /- 14 ) months . After 3 years of clinical service , three biologic and five technical failures were recorded . All failures occurred in the FDP group . One FDP was removed after biologic failure of one abutment tooth . The Kaplan-Meier survival probability was 88.2 % after 35 months for all types of failures and 98.5 % concerning restorations in service . The type of restoration showed significant influence on the survival probability ( P < .001 , log-rank test ) . No influence on gingival parameters from the restorations was observed compared to control teeth . CONCLUSIONS Zirconia substructures veneered with fluorapatite veneering porcelain seem to be a reliable treatment option . More research has to be conducted to investigate differences between single crowns and FDPs PURPOSE The objective of this follow-up study was to examine the performance of Cerec inlays and onlays in terms of clinical quality over a functional period of 10 years . MATERIAL S AND METHODS Of 200 Cerec inlays and onlays placed in a private practice between 1989 and early 1991 , 187 restorations were observed over a period of 10 years . The restorations were fabricated chairside using the Cerec-1 computer-aided design /manufacturing ( CAD/CAM ) method and Vita MK I feldspathic ceramic . An adhesive technique and luting composite resin were used for seating the restorations . After 10 years , the clinical performance of the restorations was evaluated using modified USPHS criteria . The results were used to classify success and failure . RESULTS According to Kaplan-Meier analysis , the success rate of Cerec inlays and onlays dropped to 90.4 % after 10 years . A total of 15 ( 8 % ) failures were found in 11 patients . Of these failures , 73 % were caused by either ceramic fractures ( 53 % ) or tooth fractures ( 20 % ) . The reasons for the remaining failures were caries ( 20 % ) and endodontic problems ( 7 % ) . The three-surface Cerec reconstructions were found to have the most failures . CONCLUSION The failure rate of 8 % and the drop of the survival probability rate to 90.4 % after 10 years of clinical service of Cerec-1 CAD/CAM restorations made of Vita MK I feldspathic ceramic appear to be acceptable in private practice . This is particularly true in light of the very high patient satisfaction Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results This study prospect ively evaluated the clinical performance of computer-assisted design and computer-assisted manufacturing (CAD/CAM)-generated In-Ceram Alumina core crowns in Japanese patients for up to 5 years . A total of 101 In-Ceram crowns with aluminium copings fabricated using the GN-I system were placed in Japanese patients . The crowns were evaluated using a California Dental Association ( CDA ) quality assessment system at baseline and at all follow-up examinations . Gingival condition was assessed using plaque and bleeding scores . The survival of anterior and posterior crowns was analysed according to the Kaplan-Meier method . The scores of gingival condition were compared between restored crowns and contralateral teeth using a t-test . During the observation period , six crowns were lost to follow-up . Five crowns were fractured from the copings and removed , and four crowns were removed for other reasons . Chipping within the porcelain was detected in three crowns , which were then polished . The cumulative survival rates after 60 months were 96·9 % for anterior crowns and 87·7 % for posterior ones , and there were no significant differences between anterior and posterior crowns . According to the CDA criteria , most of the crowns were rated as satisfactory during the observation period . There were significant differences in soft tissue conditions between In-Ceram crowns and control teeth at 2- and 5-year examinations . Despite the five fractures from copings , In-Ceram Alumina crowns with copings fabricated using the CAD/CAM ( GN-I system ) for replacing both anterior and posterior teeth showed predictable results during a 5-year observation period OBJECTIVE The aim of this study was to evaluate the clinical performance of ceramic inlays made from machinable ceramic blocks . METHOD AND MATERIAL S The 2 inlay systems involved computer-aided design and computer-aided machining ( Cerec Cos 2.1 ) or copy-milling technique ( Celay ) . The study comprised 15 Celay inlays and 15 Cerec inlays placed in 17 patients . The inlays were evaluated clinical ly at baseline ( 1 week ) as well as 1 and 3 years later ( modified California Dental Association quality evaluation system ) . RESULTS One Celay inlay fractured after 1 year of service , and 2 Cerec inlays were replaced , 1 after 6 months and 1 after 1 year , because of pulpal pain and persisting hypersensitivity . One Celay inlay lost retention after 2 years . At the 3-year evaluation , chipping and hairline cracks were seen in 2 Celay inlays . Progressive disintegration of the marginal luting cement was seen for both Celay and Cerec inlays . The remaining 25 inlays performed satisfactorily throughout the 3-year period . CONCLUSION Because of their relatively high failure rate , these inlays should be reserved for esthetic indications The authors conducted a long-term clinical study of 50 CEREC ( Siemens AG ) CAD-CAM inlay restorations in 28 patients . After four years , they found the inlays to rate very highly in color matching , interfacial staining , secondary caries , anatomic contour , marginal adaptation , surface texture and postoperative sensitivity . They monitored cement loss along the occlusal margins and found it to be relatively low , with an unusual decrease in measured cement wear from the third to the fourth year . The favorable results of this long-term clinical study of these CAD-CAM restorations portend significant success for this restorative approach Procera AllCeram crowns were prospect ively evaluated clinical ly in both anterior and posterior regions in Japanese . One-hundred and one crowns were fabricated for 57 patients at the Tsurumi University Dental Hospital from August 2001 to October 2002 and evaluated according to the California Dental Association ( CDA ) quality evaluation system at baseline and annually at all follow-up examinations for 5 years . The plaque index ( PI ) and gingival index ( GI ) were recorded , and chipping and fracture were checked at the same time as well . A total of 75 Procera AllCeram crowns were evaluated , and the cumulative survival rate was 90.2 % over the 5-year clinical trial . Six crowns experienced fractures within the veneering porcelain and from aluminium oxide coping , all of which occurred on the premolar and molar regions , and they had to be removed . Small chipping was observed on three crowns . According to the CDA criteria , 98 % of Procera AllCeram crowns were rated as satisfactory , and PI and GI were comparable to those of control teeth during the observation period The purpose of this study was to evaluate Cerec CAD/CAM inlays processed of two industrially made machinable ceramics during an 8-yr follow-up period . Each of 16 patients received two similar ceramic inlays . Half the number of the inlays were made of a feldspathic ( Vita Mark II ) and the other of a glass ceramic ( Dicor MGC ) block . The inlays were luted with a dual resin composite and evaluated clinical ly using modified USPHS criteria at baseline , 8 months , 2 , 3 , 5 , 6 and 8 yr , and indirectly using models . At baseline , 84 % of the inlays were estimated as optimal and 16 % as acceptable . Postoperative sensitivity was reported by one patient for 8 months . Of the 32 inlays evaluated during the 8 yr , 3 failed due to fracture of the material . No secondary caries was found adjacent to the inlays . No significant differences in the clinical performance were found between inlays made of the two ceramics . It can be concluded that the CAD/CAM inlays processed of the two ceramics functioned well during the 8-yr follow-up period The aim of this prospect i ve r and omised controlled clinical trial was to evaluate the clinical outcome of shrinkage-free ZrSiO4 -ceramic full-coverage crowns on premolars and molars in comparison with conventional gold crowns over a 5-year period . Two hundred and twenty-three patients were included and r and omly divided into two treatment groups . One hundred and twenty-three patients were restored with 123 ZrSiO4 -ceramic crowns , and 100 patients received 100 gold crowns , which served as the control . All crowns were conventionally cemented with glass-ionomer cement . After an observation period of 6 , 12 , 24 , 36 , 48 and 60 months , the survival probability ( Kaplan-Meier ) for the shrinkage-free ZrSiO4 -ceramic crowns was 98·3 % , 92·0 % , 84·7 % , 79 % and 73·2 % and for the gold crowns , 99 % , 97·9 % , 95·7 % , 94·6 % and 92·3 % , respectively . The difference between the test and control group was statistically significant ( P = 0·0027 ) . The gold crowns showed a better marginal integrity with less marginal discoloration than the ceramic crowns . The most common failure in the ceramic crown group was fracture of the crown . The 60-month results of this prospect i ve r and omised controlled clinical trial suggest that the use of these shrinkage-free ZrSiO4 -ceramic crowns in posterior tooth restorations can not be recommended This study dealt with the clinical evaluation of 121 inlays and onlays generated from both Dicor ceramics and Vita porcelains . These two different types of ceramic material s were cemented using three different duo-cured composite resin luting agents , which differed in particle size . At the end of 3 years , no difference could be detected between the clinical performance of the Dicor and Vita restorations . Both exhibited the same degree of color matching characteristics , marginal integrity , and general clinical performance ; however , seven of the restorations exhibited fracture through the isthmus , which was shown to be due to insufficient cavity depth . The balance of the restorations exhibited excellent clinical performance when evaluated against the United States Public Health Service System BACKGROUND Adhesively luted all-ceramic restorations preserve and stabilize weakened tooth structure , but there is little published information about the clinical performance of large , all-ceramic restorations . METHODS In this pilot study , the authors placed 58 large , single-tooth , all-ceramic restorations in 26 patients using a computer-aided design /computer-aided manufacturing , or CAD/CAM , system ( CEREC 2 , Sirona Dental Systems GmbH , Bensheim , Germany ) . They documented the maximum height of the restoration and remaining cementoenamel junction , or CEJ . In 21 cases , rubber dam isolation was not possible during adhesive luting . They re-evaluated the restorations after three years according to the U.S. Public Health Service criteria . RESULTS After three years , the authors rated 56 ( 97 percent ) of the 58 restorations as Bravo or better in regard to marginal integrity , secondary caries ( four could not be rated ) , discoloration and anatomical form . One restoration was rated as Charlie because of poor marginal integrity , and one restoration had to be replaced owing to a bulk fracture . The authors rated the adequacy of proximal contact and occlusal relationships as acceptable-to-good for all restorations . Neither the extent of the remaining enamel at the cavity margin nor application of a rubber dam had any statistically significant influence ( chi2 test , P > .05 ) on the clinical performance of the restorations after three years . CONCLUSIONS At the three-year recall appointment , the authors found that the adhesively luted all-ceramic restorations had successfully repaired large coronal defects , irrespective of the cavity margin location ( that is , coronal or apical to the CEJ ) . CLINICAL IMPLICATION S Tooth-colored , all-ceramic CAD/CAM-generated restorations are an alternative to conventional restorations if large coronal defects need to be treated Anterior mono-ceramic ( Mk II , n = 18 ) and ceramic core ( In-Ceram Spinell , n = 18 ) crowns were CAD/CAM-fabricated using Vitablocs with the Cerec 2 CAD/CAM system and bonded in 24 patients . All crowns were rated using modified United States Public Health Services ( USPHS ) criteria at baseline and after a service time of 2 - 5 years . Survival of the crowns , regarding fracture , was analysed ( Kaplan-Meier ) after 44.7 + /- 10.3 months . Gingival health at crowns was assessed using plaque and bleeding scores . One core crown and one mono-ceramic crown had fractured after 42.5 months and 12 months , respectively , with survival rates of 91.7 % for In-Ceram Spinell and 94.4 % for Mk II ; the difference was not statistically significant . Between baseline and follow-up examinations , non-significant shifts from A- to B-ratings occurred , particularly for marginal adaptation , for both crown types . Plaque and bleeding scores did not differ between the ceramic crown types but showed significantly less plaque and less bleeding at ceramic crowns than at control teeth at follow-up . The clinical performance of mono-ceramic crowns was judged to be similar to that of ceramic core crowns PURPOSE To investigate the long-term clinical performance of cast gold partial crowns ( CGPCs ) as compared to partial ceramic crowns ( PCCs ) . The null hypothesis tested was that CGPCs and PCCs would show similar clinical outcomes . In the present evaluation , the 5.5 year results are reported . METHODS This was a controlled , prospect i ve , clinical split-mouth study . In each patient , one CGPC ( Degulor C ) and one PCC ( Vita Mark II ceramic/Cerec 3 ) had been inserted at baseline . After 5.5 years , 22 CGPC and 22 PCC restorations in 22 subjects attending the recall visit were clinical ly assessed using modified United States Public Health Service ( USPHS ) criteria . Kaplan-Meier survival rates were calculated for CGPCs and PCCs of the 29 subjects who had been originally enrolled in the study . RESULTS 22 subjects ( 8 male , 14 female ) participated in the 5.5-year recall with a total of 44 restorations . 22 CGPCs and 11 PCCs were placed in molars ; 11 PCCs were placed in premolars . The median patient age was 37 years ( 32 - 44 years ) . All subjects revealed a papilla bleeding index ( PBI ) of < 20 % ( median : 7 % ) . After 5.5 years , PCCs revealed a statistically significant , time dependant decrease of Alfa ratings for criteria anatomic form , marginal adaptation and marginal discoloration . Furthermore , PCCs as compared to CGPCs showed a statistically significant material -related decrease of Alfa ratings for criteria anatomic form and marginal discoloration . Kaplan-Meier survival analysis revealed a 93.3 % cumulative survival rate for CGPCs and an 88.8 % cumulative survival rate for PCCs after 5.5 years . Survival functions did not differ significantly across groups . At 5.5 years , CGPCs and PCCs exhibited satisfactory clinical outcomes . For PCCs , Bravo ratings increased significantly over time , however this did not compromise clinical survival of the restorations as compared to CGPCs The gathering of clinical data on fractures of dental restorations through prospect i ve clinical trials is a labor- and time-consuming enterprise . Here , we propose an unconventional approach for collecting large data sets , from which clinical information on indirect restorations can be retrospectively analyzed . The authors accessed the data base of an industry-scale machining center in Germany and obtained information on 34,911 computer-aided design (CAD)/computer-aided manufacturing ( CAM ) all-ceramic posterior restorations . The fractures of bridges , crowns , onlays , and inlays fabricated from different all-ceramic systems over a period of 3.5 y were reported by dentists and entered in the data base . Survival analyses and estimations of future life revealed differences in performance among ZrO2-based restorations and lithium disilicate and leucite-reinforced glass-ceramics Objectives The objective of this prospect i ve clinical study was to evaluate the performance of chair-side generated crowns after 48 months . Material s and methods Forty-one posterior full contour crowns made of a machinable lithium disilicate ceramic ( e.max CAD LT ) were inserted in 34 patients applying a chair-side CAD/CAM technique . One crown per patient was r and omly selected for evaluation at baseline , after 6 , 12 , 24 , 36 , and 48 months according to modified US Public Health Service criteria . Results After a mean observation time of 51 months ( min , 48 months ; max , 56 months ; SD ± 2.3 months ) , 29 crowns were available for re-examination . Within the observation period , one failure occurred due to a crown fracture after 2.8 years . Four abutment teeth revealed signs of biological complications : Two abutment changed sensibility perception from positive to negative within the first 13 month . Two abutment teeth showed secondary caries below the crown margin , one after the 24 , and another after the 48 month recall . Both abutments received cervical adhesive composite fillings . The failure-free rate was 96.3 % after 4 years according to Kaplan – Meier ( CI : upper bound , 4.4 years ; lower bound , 4.7 years ) . Conclusions Due to the fact that the secondary caries was not caused as a result of an inaccuracy of the crown margins and the endodontic complications were in a normal range , the clinical performance of the crowns was completely satisfying . Clinical relevance The chair-side application of lithium disilicate crowns can be recommended PURPOSE No clinical evidence has been provided to suggest that metal-free all-composite resin indirect restorations are a functional and esthetic alternative to all-ceramic restorations . The aim of this study was to evaluate the clinical performance of single-tooth computer-aided design /computer-assisted manufacturing (CAD/CAM)-generated all-composite resin and all-ceramic crowns after 3 years of function . MATERIAL S AND METHODS In a prospect i ve trial , 200 all-composite resin and all-ceramic crowns were rated over a 3-year period . Restorations were evaluated at 3 weeks and 1 and 3 years after insertion by the California Dental Association quality evaluation index , the patient 's self- assessment , marginal fit , periodontal parameters , volume loss , and wear patterns of the veneering material . Statistical analysis was performed using t tests ( a = .05 ) . RESULTS Cumulative survival and success rates after 3 years were 87.9 % and 55.6 % for all-composite resin and 97.2 % and 81.2 % for all-ceramic crowns , respectively ( P < .05 for success rates ) . Restoration loosening occurred exclusively for all-composite resin crowns cemented on a cast post . All-ceramic restorations demonstrated satisfactory esthetic results . All-composite resin crowns result ed in significantly more mean total volume loss and mean vertical wear at occlusal contact areas after 6 months and 3 years of function . The clinical performance of the CAD/CAM-generated all-ceramic crowns used in this study was similar to that of other all-ceramic CAD/CAM systems . CONCLUSION For up to 3 years of function , all-composite resin single-tooth restorations have inferior success rates compared to all-ceramic restorations . Due to the inferior esthetics and wear resistance of all-composite resin crowns , all-ceramic crowns remain the preferred treatment for CAD/CAM-generated metal-free single-tooth restorations OBJECTIVES Midterm-evaluation of a 5-year prospect i ve clinical splitmouth-investigation on survival rate and long-term behavior of all-ceramic partial coverage restorations ( PCRs ) on molars . Pressed ceramic and CAD/CAM fabricated PCRs were compared . METHODS 80 vital molars of 25 patients were restored with all-ceramic PCRs ( 40 IPS e.max Press*[IP ] and 40 ProCAD*[PC ] ) . IP-PCRs were heat pressed following the lost-wax method . PC-PCRs were fabricated with Cerec 3 * * and Cerec InLab * * CAD/CAM system ( * * Sirona Dental Systems , Bensheim , Germany ) . All PCRs were adhesively luted with a light-polymerizing composite ( Syntac*/Tetric * ) ( * Ivoclar Vivadent , Schaan , Liechtenstein ) . Clinical reevaluations were performed at baseline and 13 , 25 , and 36 months after insertion of the PCRs according to the modified United States Public Health Services ( USPHS ) criteria . Absolute failures were demonstrated by Kaplan-Meier survival rate . RESULTS After an observation time up to 3 years , survival rate of IP-PCRs was 100 % and 97 % for PC-PCRs due to one severe fracture . The PC-PCR had to be replaced after 9 months . Secondary caries and endodontic complications did not occur . Increased clinical service time result ed in significant decrease of marginal adaptation ( p=0.031 ) and enhanced marginal discoloration ( p<0.0001 ) . Both PCR ceramic material s demonstrated significant deteriorations in color match ( p<0.0001 ) and surface roughness ( p<0.0001 ) , IP-PCRs were significantly more affected ( p < or = 0.005 ) . Regarding anatomic form IP-PCRs performed significantly better ( p=0.0012 ) . CONCLUSION Pressed ceramic and CAD/CAM fabricated partial coverage restorations exhibited a reliable treatment option to restore larger defects in posterior teeth . Marginal degradation of the resin cement and deterioration of the all-ceramic material s during clinical function determine the clinical long-term performance of partial coverage restorations |
10,362 | 31,791,341 | Conclusions Implementation model use was predominately centered on the interpretation of results and analyses , with few examples of use across all study phases as a planning tool and to underst and results .
This lack of implementation models applied may explain the limited success of interventions when delivered under real-world conditions or at scale . | Background Globally , many children fail to meet the World Health Organization ’s physical activity and sedentary behaviour guidelines .
Schools are an ideal setting to intervene , yet despite many interventions in this setting , success when delivered under real-world conditions or at scale is limited . | OBJECTIVE Assessed the feasibility , acceptability , and sustainability of Planet Health , an interdisciplinary , integrated health education curriculum implemented in six public middle schools . METHODS Workshops on Planet Health implementation were attended by 129 teachers ( language arts , math , science , and social studies ) over three school years ( 1999 - 2000 , 2000 - 2001 , and 2001 - 2002 ) . Question naires were administered post-implementation and in the fall and spring of each year . Outcomes were dose , acceptability , feasibility , and intent to continue use . RESULTS The average number of lessons taught per teacher per year was 1.7 to 3.1 , compared to a goal of 2 to 3 . Each year , teachers reported high acceptability and perceived feasibility of the intervention , and the majority indicated they intended to continue using the curriculum . CONCLUSIONS Planet Health was feasible and acceptable in a participatory research model involving a public school-university partnership , and it was also sustainable independent of the research effort 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 The evidence -based Dutch Obesity Intervention in Teenagers ( DOiT ) program is a school-based obesity prevention program for 12 to 14-year olds attending the first two years of prevocational education . This paper describes the study protocol applied to evaluate ( a ) the nationwide dissemination process of DOiT in the Netherl and s , and ( b ) the relationship between quality of implementation and effectiveness during nationwide dissemination of the program in the Netherl and s. Methods In order to explore facilitating factors and barriers for dissemination of DOiT , we monitored the process of adoption , implementation and continuation of the DOiT program among 20 prevocational schools in the Netherl and s. The study was an observational study using qualitative ( i.e. semi-structured interviews ) and quantitative methods ( i.e. question naires and logbooks ) . Eight process indicators were assessed : recruitment , context , reach , dosage , fidelity , satisfaction , effectiveness and continuation . All teachers , students and parents involved in the implementation of the program were invited to participate in the study . As part of the process evaluation , a cluster-controlled trial with ten control schools was conducted to evaluate the effectiveness of the program on students ’ anthropometry and energy balance-related behaviours and its association with quality of implementation . Discussion The identified impeding and facilitating factors will contribute to an adjusted strategy promoting adoption , implementation and continuation of the DOiT program to ensure optimal use and , thereby , prevention of obesity in Dutch adolescents . Trial registration Current Controlled Trials IS RCT N92755979 Reconnecting Youth ( RY ) is a school-based drug prevention program design ed to address academic , substance use and mood management goals among youth at risk of dropping out of high school . This paper presents the organizational factors and RY program characteristics that either promoted or hindered the implementation of the program during a r and omized controlled effectiveness trial in 10 schools in two school districts in the United States . Data were collected using surveys and interviews from teachers and school and district staff who participated in the implementation of the RY program in these schools . Results suggest that certain RY program characteristics made it difficult to implement . Small class size , re source -intensive procedures for student selection and recruitment and special training , qualities and skills needed to be an effective RY teacher meant that schools had to significantly change their usual practice s to implement the program . Organizational barriers included a lack of financial re sources and leadership support for program implementation , and low priority for non-academic courses for high-risk students . Transient student population s , staff turnover and district-wide scheduling and curriculum changes all result ed in high levels of organizational turbulence at most schools , further hindering program implementation Research consistently indicates that schools fail to implement m and atory physical activity policies . This review aim ed to describe factors ( barriers and facilitators ) that may influence the implementation of school physical activity policies which specify the time or intensity that physical activity should be implemented and to map these factors to a theoretical framework . A systematic search was undertaken in six data bases for quantitative or qualitative studies published between 1995-March 2016 that examined teachers ' , principals ' or school administrators ' reported barriers and /or facilitators to implementing m and ated school physical activity policies . Two independent review ers screened texts , extracted and coded data from identified articles using the Theoretical Domains Framework ( TDF ) . Of the 10,346 articles identified , 17 studies met the inclusion criteria ( 8 quantitative , 9 qualitative ) . Barriers and facilitators identified in qualitative studies covered 9 and 10 TDF domains respectively . Barriers and facilitators reported in quantitative studies covered 8 TDF domains each . The most common domains identified were : ' environmental context and re sources ' ( e.g. , availability of equipment , time or staff ) , ' goals ' ( e.g. , the perceived priority of the policy in the school ) , ' social influences ' ( e.g. , support from school boards ) , and ' skills ' ( e.g. , teachers ' ability to implement the policy ) . Implementation support strategies that target these factors may represent promising means to improve implementation of physical activity policies and increase physical activity among school-aged children . Future studies assessing factors that influence school implementation of physical activity policies would benefit from using a comprehensive framework to help identify if any domains have been overlooked in the current literature . REGISTRATION This review was prospect ively registered with PROSPERO ( CRD42016051649 ) on the 8th December 2016 Background A fundamental challenge of implementation is identifying context ual determinants ( i.e. , barriers and facilitators ) and determining which implementation strategies will address them . Numerous conceptual frameworks ( e.g. , the Consoli date d Framework for Implementation Research ; CFIR ) have been developed to guide the identification of context ual determinants , and compilations of implementation strategies ( e.g. , the Expert Recommendations for Implementing Change compilation ; ERIC ) have been developed which can support selection and reporting of implementation strategies . The aim of this study was to identify which ERIC implementation strategies would best address specific CFIR-based context ual barriers . Methods Implementation research ers and practitioners were recruited to participate in an online series of tasks involving matching specific ERIC implementation strategies to specific implementation barriers . Participants were presented with brief descriptions of barriers based on CFIR construct definitions . They were asked to rank up to seven implementation strategies that would best address each barrier . Barriers were presented in a r and om order , and participants had the option to respond to the barrier or skip to another barrier . Participants were also asked about considerations that most influenced their choices . Results Four hundred thirty-five invitations were emailed and 169 ( 39 % ) individuals participated . Respondents had considerable heterogeneity in opinions regarding which ERIC strategies best addressed each CFIR barrier . Across the 39 CFIR barriers , an average of 47 different ERIC strategies ( SD = 4.8 , range 35 to 55 ) was endorsed at least once for each , as being one of seven strategies that would best address the barrier . A tool was developed that allows users to specify high-priority CFIR-based barriers and receive a prioritized list of strategies based on endorsements provided by participants . Conclusions The wide heterogeneity of endorsements obtained in this study ’s task suggests that there are relatively few consistent relationships between CFIR-based barriers and ERIC implementation strategies . Despite this heterogeneity , a tool aggregating endorsements across multiple barriers can support taking a structured approach to consider a broad range of strategies given those barriers . This study ’s results point to the need for a more detailed evaluation of the underlying determinants of barriers and how these determinants are addressed by strategies as part of the implementation planning process Background . The aim of the present study was to investigate factors influencing the adoption , implementation , and institutionalization process of JUMP-in — a multilevel school-based physical activity promotion program — to optimize the dissemination of the intervention and improve its effectiveness . The process evaluation concerned the constraints and success and failure factors at sociopolitical , organizational , user , and intervention levels . Methods . A mixed methods approach including qualitative and quantitative data was conducted during two school years ( 2006 - 2008 ) . Results . JUMP-in was successfully embedded in the Amsterdam municipal policy and in the organizational structure and daily practice s of the sectors involved . A general impeding factor was the complexity of the multilevel programme requiring multidisciplinary collaboration between organizations . In addition , there was a discrepancy between the recommendation to st and ardize and simplify the innovation and the need to tailor the strategies to local environmental , social , and cultural aspects . Conclusions . This process evaluation provides challenges and remedies for managing discrepancies between prerequisites for an effective innovation and dem and s of daily implementation practice . The main recommendations are ( a ) st and ardized , simplified guidelines ; ( b ) stepwise implementation ; ( c ) formalized coalitions , integration of policy , and synchronization of tasks and protocol s ; and ( d ) smart planning and control by clear communication and feedback instruments . If these recommendations are incorporated into the JUMP-in intervention and organization , increased effectiveness and long-term effects can be expected |
10,363 | 26,055,986 | Conclusions Despite low quality evidence , the direction and consistency of effects indicate that housing is an important risk factor for malaria . | Background The global malaria burden has fallen since 2000 , sometimes before large-scale vector control programmes were initiated .
While long-lasting insecticide-treated nets and indoor residual spraying are highly effective interventions , this study tests the hypothesis that improved housing can reduce malaria by decreasing house entry by malaria mosquitoes . | Background In many parts of continental Africa house construction does not appear to impede entry of malaria vectors and , given their generally late biting cycle , the great majority of transmission takes place indoors . In contrast , many houses in São Tomé , 140 km off the coast of Gabon , are raised on stilts and built of wooden planks . Building on stilts is a time-honoured , but largely untested , way of avoiding mosquito bites . Exposure may also be affected by mosquito activity times and age composition of host-seeking females . A study was therefore undertaken on the isl and of São Tomé to determine if exposure to Anopheles gambiae , the only vector on the isl and , varied with house construction or time of the night . Methods A series of all-night l and ing collection s were undertaken out of doors at ground level , inside houses at ground level , on the ver and as of , and inside houses built on stilts . The gonotrophic age of an unselected sample of insects from the first three hours of l and ing collection ( 18:00–21:00 ) was determined by dissection . In addition , 1,149 miniature light-trap collection s were obtained from 125 houses in the study area . Numbers collected were related to house construction . Results Biting of An . gambiae took place primarily outside at ground level . Less than one third of biting occurred inside houses . Houses built on stilts had half the number of An . gambiae in them compared to those built at ground level . Conversely houses with an eaves gap had more An . gambiae in them than houses without such a gap . Gonotrophic age did not affect house entry rates in An . gambiae . House construction affected Culex quinquefasciatus less than An . gambiae . Mean density per house , derived from a series of 1,490 r and omly assigned light-trap collection s , was over-dispersed with 18 % of houses having 70 % of the vectors . Conclusion House construction plays an important role in determining exposure to malaria vectors in São Tomé . Neighbours can have very different exposure levels . Recommendations for improvement in control are given Background One of the best ways to control the transmission of malaria is by breaking the vector-human link , either by reducing the effective population size of mosquitoes or avoiding infective bites . Reducing house entry rates in endophagic vectors by obstructing openings is one simple way of achieving this . Mosquito netting has previously been shown to have this effect . More recently different material s that could also be used have come onto the market . Therefore , a pilot study was conducted to investigate the protective effect of three types of material against Anopheles funestus and Anopheles gambiae s.l entry into village houses in Mozambique when applied over the large opening at the gables and both gables and eaves . Methods A two-step intervention was implemented in which the gable ends of houses ( the largest opening ) were covered with one of three material s ( four year old mosquito bed nets ; locally purchased untreated shade cloth or deltamethrin-impregnated shade cloth ) followed by covering both gable ends and eaves with material . Four experimental rounds ( each of three weeks duration ) , from four houses r and omly assigned to be a control or to receive one of the three intervention material s , were undertaken from March to August 2010 in the village of Furvela in southern Mozambique . Mosquito entry rates were assessed by light-trap collection and the efficacy of the different material s was determined in terms of incidence rate ratio ( IRR ) , obtained through a Generalized Estimating Equations ( GEE ) , of mosquito entry in a treated house compared to the untreated ( control ) house . Results Altogether 9,692 An . funestus and 1,670 An . gambiae s.l . were collected . Houses treated with mosquito netting or the untreated shade cloth had 61.3 % [ IRR = 0.39 ( 0.32 - 0.46 ) ; P < 0.0001 ] and 70 % [ IRR = 0.30 ( 0.25 – 0.37 ) ; P < 0.001 ] fewer An . funestus in relation to untreated houses , but there was no difference in An . funestus in houses treated with the deltamethrin-impregnated shade cloth [ IRR = 0.92 ( 0.76 –1.12 ) ; P = 0.4 ] compared to untreated houses . Houses treated with mosquito netting reduced entry rates of An . gambiae s.l , by 84 % [ IRR = 0.16 ( 0.10 – 0.25 ) ; P < 0.001 ] , whilst untreated shade cloth reduced entry rates by 69 % [ IRR = 0.31 ( 0.19 –0.53 ) ; P < 0.001 ] and entry rates were reduced by 76 % [ IRR = 0.24 ( 0.15 0.38 ) ; P < 0.001 ] in houses fitted with deltamethrin-impregnated shade cloth OBJECTIVE To identify risk factors for uncomplicated malaria in highl and areas of East Africa at higher risk of malaria epidemics , in order to design appropriate interventions . METHODS Prospect i ve , population -based , case-control study in the N and i Hills , a highl and area of western Kenya , to identify environmental , sociodemographic and behavioural factors associated with clinical malaria . Data were collected using field observation , a structured question naire , and a global positioning system device . RESULTS We interviewed 488 cases of slide-confirmed malaria and 980 age-matched controls . Multivariate analyses associated higher malaria risk with living < 250 m of a forest [ OR = 3.3 ( 95 % CI 1.5 , 7.1 ) ] , < 250 m of a swamp [ 2.8 ( 1.3 , 5.9 ) ] , < 200 m of maize fields [ 2.0 ( 1.2 , 3.4 ) ] , in the absence of trees < 200 m [ 1.6 ( 1.2 , 2.2 ) ] , on flat l and [ 1.6 ( 1.2 , 2.2 ) ] , in houses without ceilings [ 1.5 ( 1.1 , 2.2 ) ] , in houses with a separate kitchen building [ 1.8 ( 1.4 , 2.3 ) ] and in households where the female household head had no education [ 1.9 ( 1.1 , 3.1 ) ] . Travelling out of the study site [ 2.2 ( 1.2 , 4.1 ) ] was also associated with increased risk . CONCLUSIONS ; In this East African highl and area , risk of developing uncomplicated malaria was multifactorial with a risk factor profile similar to that in endemic regions . Households within close proximity to forest and swamp borders are at higher risk of malaria and should be included in indoor residual spraying campaigns Background Several studies conducted in Northeast Tanzania have documented declines in malaria transmission even before interventions were scaled up . One explanation for these reductions may be the changes in socio-environmental conditions associated with economic development , and in particular improvements in housing construction . Objective This analysis seeks to identify ( 1 ) risk factors for malaria incidence among young children and ( 2 ) household and environmental factors associated with mosquito vector numbers collected in the child ’s sleeping area . Both analyses focus on housing construction quality as a key determinant . Methodology For 435 children enrolled in a larger trial of intermittent preventive treatment for malaria in infants in the Korogwe District in Tanga , Northeastern Tanzania , detailed information on their dwelling characteristics were collected in the last year of the trial . Principal components analysis was used to construct an index of housing structure quality and converted to quintile units for regression analysis . Univariate and multivariate r and om effects negative binomial regressions were used to predict risk factors for child malaria incidence and the mean total number of indoor female Anopheles gambiae and funestus mosquitoes collected per household across three occasions . Findings Building material s have substantially improved in Korogwe over time . Multivariate regressions showed that residing in rural areas ( versus urban ) increased malaria incidence rates by over three-fold and mean indoor female A. gambiae and funestus numbers by nearly two-fold . Compared to those residing in the lowest quality houses , children residing in the highest quality houses had one-third lower malaria incidence rates , even when wealth and rural residence were controlled for . Living in the highest quality houses reduced vector numbers while having cattle near the house significantly increased them . Conclusions Results corroborate findings from other studies that show associations between malaria incidence and housing quality ; associations were concentrated amongst the highest quality houses Background Underst and ing the role of local environmental risk factors for malaria in holo-endemic , poverty-stricken setting s will be critical to more effectively implement- interventions aim ed at eventual elimination . Household-level environmental drivers of malaria risk during the dry season were investigated in rural southern Malawi among children < five years old in two neighbouring rural Traditional Authority ( TA ) regions dominated by small-scale agriculture . Methods Ten villages were r and omly selected from TA Sitola ( n = 6 ) and Nsamala ( n = 4 ) . Within each village , during June to August 2011 , a census was conducted of all households with children under-five and recorded their locations with a geographic position system ( GPS ) device . At each participating house , a nurse administered a malaria rapid diagnostic test ( RDT ) to children under five years of age , and a question naire to parents . Environmental data were collected for each house , including l and cover within 50-m radius . Variables found to be significantly associated with P. falciparum infection status in bivariate analysis were included in generalized linear models , including multivariate logistic regression ( MLR ) and multi-level multivariate logistic regression ( MLLR ) . Spatial clustering of RDT status , environmental factors , and Pearson residuals from MLR and MLLR were analysed using the Getis-Ord Gi * statistic . Results Of 390 children enrolled from six villages in Sitola ( n = 162 ) and four villages in Nsamala ( n = 228 ) , 45.6 % tested positive ( n = 178 ) for Plasmodium infection by RDT . The MLLR modelled the statistical relationship of Plasmodium positives and household proximity to agriculture ( < 25-m radius ) , controlling for the child sex and age ( in months ) , bed net ownership , elevation , and r and om effects intercepts for village and TA-level unmeasured factors . After controlling for area affects in MLLR , proximity to active agriculture remained a significant predictor of positive RDT result ( OR 2.80 , 95 % CI 1.41 - 5.55 ) . Mapping of Pearson residuals from MLR showed significant clustering ( Gi * z > 2.58 , p < 0.01 ) predominantly within TA Sitola , while residuals from MLLR showed no such clustering . Conclusion This study provides evidence for significant , dry-season heterogeneity of malaria prevalence strongly linked to peridomestic l and use , and particularly of elevated risk associated with nearby crop production Background Identification and better underst and ing of potential risk factors for malaria are important for targeted and cost-effective health interventions . Housing conditions have been suggested as one of the potential risk factors . This study aims to further investigate this risk factor , and is focused on the effect of the type of roof on Plasmodium falciparum infection among children below five years in the North West of Burkina Faso . Methods In a cross-sectional study design , 661 children aged six to 60 months were r and omly selected from three rural and one semi-urban site at the end of the rainy season ( November 2003 ) . The children were screened for fever and tested for Plasmodium falciparum infection . In addition , data on bed net use and house characteristics was collected from the household were each child lived . Using adjusted odds ratios , children living in house roofed with iron-sheet were compared with those in house with mud or grass roof . Results Overall P. falciparum infection prevalence was 22.8 % with a significant variation between ( Chi-square , p < 0.0001 ) . The prevalence in Cissé ( 33.3 % ) and Goni ( 30.6 % ) were twice times more than in Nouna ( 15.2 % ) and Kodougou ( 13.2 % ) . After adjusting for age , sex , use of bed net and housing conditions , children living in houses with mud roofs had significantly higher risk of getting P. falciparum infection compared to those living in iron-sheet roofed houses ( Odds Ratio 2.6 ; 95 % Confidence Interval , 1.4–4.7 ) . Conclusion These results suggest that house characteristics should be taken into consideration when design ing health intervention against P. falciparum infection and particular attention should be paid to children living in houses with mud roofs Background In the pre-intervention year of a r and omized controlled trial investigating the protective effects of house screening against malaria-transmitting vectors , a multi-factorial risk factor analysis study was used to identify factors that influence mosquito house entry . Methods Mosquitoes were sample d using CDC light traps in 976 houses , each on one night , in Farafenni town and surrounding villages during the malaria-transmission season in The Gambia . Catches from individual houses were both ( a ) left unadjusted and ( b ) adjusted relative to the number of mosquitoes caught in four sentinel houses that were operated nightly throughout the period , to allow for night-to-night variation . Houses were characterized by location , architecture , human occupancy and their mosquito control activities , and the number and type of domestic animals within the compound . Results 106,536 mosquitoes were caught , of which 55 % were Anopheles gambiae sensu lato , the major malaria vectors in the region . There were seven fold higher numbers of An . gambiae s.l . in the villages ( geometric mean per trap night = 43.7 , 95 % confidence intervals , CIs = 39.5–48.4 ) than in Farafenni town ( 6.3 , 5.7–7.2 ) and significant variation between residential blocks ( p < 0.001 ) . A negative binomial multivariate model performed equally well using unadjusted or adjusted trap data . Using the unadjusted data the presence of nuisance mosquitoes was reduced if the house was located in the town ( odds ratio , OR = 0.11 , 95 % CIs = 0.09–0.13 ) , the eaves were closed ( OR = 0.71 , 0.60–0.85 ) , a horse was tethered near the house ( OR = 0.77 , 0.73–0.82 ) , and churai , a local incense , was burned in the room at night ( OR = 0.56 , 0.47–0.66 ) . Mosquito numbers increased per additional person in the house ( OR = 1.04 , 1.02–1.06 ) or trapping room ( OR = 1.19 , 1.13–1.25 ) and when the walls were made of mud blocks compared with concrete ( OR = 1.44 , 1.10–1.87 ) . Conclusion This study demonstrates that the risk of malaria transmission is greatest in rural areas , where large numbers of people sleep in houses made of mud blocks , where the eaves are open , horses are not tethered nearby and where churai is not burnt at night . These factors need to be considered in the design and analysis of intervention studies design ed to reduce malaria transmission in The Gambia and other parts of sub-Saharan Africa Background The goal of malaria elimination necessitates an improved underst and ing of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission . This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania . Methods Host-seeking mosquitoes were sample d from 72 r and omly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets . Spatial autocorrelation in the data set was examined using the Moran ’s I statistic and the location of any clusters was identified using the Getis-Ord Gi * statistic . Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species . Results For both Anopheles gambiae sensu lato and Anopheles funestus , the density of host-seeking females was spatially autocorrelated , or clustered . For both species , houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages . Clusters of houses with low or high densities of An . gambiae s.l . were influenced by the number of residents in nearby houses . The occurrence of high-density clusters of An . gambiae s.l . was associated with lower elevations while An . funestus was also associated with higher elevations . Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves . Conclusion The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard ( mosquito densities ) and vulnerability ( open eaves and larger households ) to malaria infection Background The highl and s of Ethiopia , situated between 1,500 and 2,500 m above sea level , experienced severe malaria epidemics . Despite the intensive control attempts , underway since 2005 and followed by an initial decline , the disease remained a major public health concern . The aim of this study was to identify malaria risk factors in highl and -fringe south- central Ethiopia . Methods This study was conducted in six rural kebeles of Butajira area located 130 km south of Addis Ababa , which are part of demographic surveillance site in Meskan and Mareko Districts , Ethiopia . Using a multistage sampling technique 750 households was sample d to obtain the 3,398 people , the estimated sample size for this study . Six repeated cross-sectional surveys were conducted from October 2008 to June 2010 . Multilevel , mixed-effects logistic regression models fitted to Plasmodium infection status ( positive or negative ) and six variables . Both fixed- and r and om-effects differences in malaria infection were estimated using median odds ratio and interval odds ratio 80 % . The odds ratios and 95 % confidence intervals were used to estimate the strength of association . Results Overall , 19,207 individuals were sample d in six surveys ( median and inter-quartile range value three ) . Six of the five variables had about two-fold to eight-fold increase in prevalence of malaria . Furthermore , among these variables , October-November survey seasons of both during 2008 and 2009 were strongly associated with increased prevalence of malaria infection . Children aged below five years ( adjusted OR= 3.62 ) and children aged five to nine years ( adj . OR= 3.39 ) , low altitude ( adj . OR= 5.22 ) , mid-level altitude ( adj . OR= 3.80 ) , houses with holes ( adj . OR= 1.59 ) , survey seasons such as October-November 2008 ( adj . OR= 7.84 ) , January-February 2009 ( adj . OR= 2.33 ) , June-July 2009 ( adj . OR=3.83 ) , October-November 2009 ( adj . OR= 7.71 ) , and January-February 2010 ( adj . OR= 3.05 ) were associated with increased malaria infection . The estimates of cluster variances revealed differences in malaria infection . The village-level intercept variance for the individual-level predictor ( 0.71 [ 95 % CI : 0.28 - 1.82 ] ; SE=0.34 ) and final ( 0.034 , [ 95 % CI : 0.002 - 0.615 ] ; SE=0.05 ) were lower than that of empty ( 0.80 , [ 95 % CI : 0.32 - 2.01 ] ; SE=0.21 ) . Conclusion Malaria control efforts in highl and fringes must prioritize children below ten years in design ing transmission reduction of malaria elimination strategy Background Good house construction may reduce the risk of malaria by limiting the entry of mosquito vectors . We assessed how house design may affect mosquito house entry and malaria risk in Ug and a. Methods 100 households were enrolled in each of three sub-counties : Walukuba , Jinja district ; Kihihi , Kanungu district ; and Nagongera , Tororo district . CDC light trap collection s of mosquitoes were done monthly in all homes . All children aged six months to ten years ( n = 878 ) were followed prospect ively for a total of 24 months to measure parasite prevalence every three months and malaria incidence . Homes were classified as modern ( cement , wood or metal walls ; and tiled or metal roof ; and closed eaves ) or traditional ( all other homes ) . Results A total of 113,618 female Anopheles were collected over 6,765 nights . 6,816 routine blood smears were taken of which 1,061 ( 15.6 % ) were malaria parasite positive . 2,582 episodes of uncomplicated malaria were diagnosed after 1,569 person years of follow-up , giving an overall incidence of 1.6 episodes per person year at risk . The human biting rate was lower in modern homes than in traditional homes ( adjusted incidence rate ratio ( IRR ) 0.48 , 95 % confidence interval ( CI ) 0.37–0.64 , p<0.001 ) . The odds of malaria infection were lower in modern homes across all the sub-counties ( adjusted odds ratio 0.44 , 95%CI 0.30–0.65 , p<0.001 ) , while malaria incidence was lower in modern homes in Kihihi ( adjusted IRR 0.61 , 95%CI 0.40–0.91 , p = 0.02 ) but not in Walukuba or Nagongera . Conclusions House design is likely to explain some of the heterogeneity of malaria transmission in Ug and a and represents a promising target for future interventions , even in highly endemic areas BACKGROUND House screening should protect people against malaria . We assessed whether two types of house screening -- full screening of windows , doors , and closing eaves , or installation of screened ceilings -- could reduce house entry of malaria vectors and frequency of anaemia in children in an area of seasonal malaria transmission . METHODS During 2006 and 2007 , 500 occupied houses in and near Farafenni town in The Gambia , an area with low use of insecticide-treated bednets , were r and omly assigned to receive full screening , screened ceilings , or no screening ( control ) . R and omisation was done by computer-generated list , in permuted blocks of five houses in the ratio 2:2:1 . Screening was not treated with insecticide . Exposure to mosquitoes indoors was assessed by fortnightly light trap collection s during the transmission season . Primary endpoints included the number of female Anopheles gambiae sensu lato mosquitoes collected per trap per night . Secondary endpoints included frequency of anaemia ( haemoglobin concentration < 80 g/L ) and parasitaemia at the end of the transmission season in children ( aged 6 months to 10 years ) who were living in the study houses . Analysis was by modified intention to treat ( ITT ) , including all r and omised houses for which there were some outcome data and all children from those houses who were sample d for haemoglobin and parasitaemia . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N51184253 . FINDINGS 462 houses were included in the modified ITT analysis ( full screening , n=188 ; screened ceilings , n=178 ; control , n=96 ) . The mean number of A gambiae caught in houses without screening was 37.5 per trap per night ( 95 % CI 31.6 - 43.3 ) , compared with 15.2 ( 12.9 - 17.4 ) in houses with full screening ( ratio of means 0.41 , 95 % CI 0.31 - 0.54 ; p<0.0001 ) and 19.1 ( 16.1 - 22.1 ) in houses with screened ceilings ( ratio 0.53 , 0.40 - 0.70 ; p<0.0001 ) . 755 children completed the study , of whom 731 had complete clinical and covariate data and were used in the analysis of clinical outcomes . 30 ( 19 % ) of 158 children from control houses had anaemia , compared with 38 ( 12 % ) of 309 from houses with full screening ( adjusted odds ratio [ OR ] 0.53 , 95 % CI 0.29 - 0.97 ; p=0.04 ) , and 31 ( 12 % ) of 264 from houses with screened ceilings ( OR 0.51 , 0.27 - 0.96 ; p=0.04 ) . Frequency of parasitaemia did not differ between intervention and control groups . INTERPRETATION House screening substantially reduced the number of mosquitoes inside houses and could contribute to prevention of anaemia in children . FUNDING Medical Research Council Summary Background The potential of insecticide-treated bednets ( ITNs ) to contribute to child survival has been well documented in r and omised controlled trials . ITN coverage has increased rapidly in Kenya from 7 % in 2004 to 67 % in 2006 . We aim ed to assess the extent to which this investment has led to improvements in child survival . Methods A dynamic cohort of about 3500 children aged 1–59 months were enumerated three times at yearly intervals in 72 rural clusters located in four districts of Kenya . The effect of ITN use on mortality was assessed with Poisson regression to take account of potential effect-modifying and confounding covariates . Findings 100 children died over 2 years . Overall mortality rates were much the same in the first and second years of the study ( 14·5 per 1000 person-years in the first year and 15·4 per 1000 person-years in the second ) . After adjustment for age , time period , and a number of other possible confounding variables , ITN use was associated with a 44 % reduction in mortality ( mortality rate ratio 0·56 , 95 % CI 0·33–0·96 ; p=0·04 ) . This level of protection corresponds to about seven deaths averted for every 1000 ITNs distributed . Interpretation A combined approach of social marketing followed by mass free distribution of ITNs translated into child survival effects that are comparable with those seen in previous r and omised controlled trials Background Screening of houses might have impact on density of indoor host-seeking Anopheles mosquitoes . A r and omized trial of screening windows and doors with metal mesh , and closing openings on eves and walls by mud was conducted to assess if reduce indoor densities of biting mosquitoes . Methods Mosquitoes were collected in forty houses using Centers for Diseases Control and Prevention ( CDC ) light traps biweekly in March and April 2011 . A r and omization of houses into control and intervention groups was done based on the baseline data . Windows and doors of 20 houses were screened by metal mesh , and openings on the walls and eves closed by mud and the rest 20 houses were used as control group . Mosquitoes were collected biweekly in October and November 2011 from both control and intervention houses . A Generalized Estimating Equations ( GEE ) with a negative binomial error distribution was used to account for over dispersion of Anopheles arabiensis and culicine counts and repeated catches made in the same house . Results Screening doors and windows , and closing openings on eves and wall by mud reduced the overall indoor densities of An . arabiensis by 40 % . The effect of screenings pronounced on unfed An . arabiensis by result ing 42 % reduction in houses with interventions . The total costs for screening windows and doors , and to close openings on the eves and walls by mud was 7.34 USD per house . ConclusionS creening houses reduced indoor density of An . arabiensis , and it was cheap and can easily incorporated into malaria vector strategies by local communities , but improving doors and windows fitness for screening should be considered during house construction to increase the efficacy of screenings Background The suppression of indoor malaria transmission requires additional interventions that complement the use of insecticide treated nets ( ITNs ) and indoor residual spraying ( IRS ) . Previous studies have examined the impact of house structure on malaria transmission in areas of low transmission . This study was conducted in a high transmission setting and presents further evidence about the association between specific house characteristics and the abundance of endophilic malaria vectors . Methods Mosquitoes were sample d using CDC light traps from 72 r and omly selected houses in two villages on a monthly basis from 2008 to 2011 in rural Southern Tanzania . Generalized linear models using Poisson distributions were used to analyze the association of house characteristics ( eave gaps , wall types , roof types , number of windows , rooms and doors , window screens , house size ) , number of occupants and ITN usage with mean catches of malaria vectors ( An.gambiae s.l . and An . funestus ) . Results A total of 36490 female An . gambiae s.l . were collected in Namwawala village and 21266 in Idete village . As for An . funestus females , 2268 were collected in Namwawala and 3398 in Idete . Individually , each house factor had a statistically significant impact ( p < 0.05 ) on the mean catches for An . gambiae s.l . but not An . funestus . A multivariate analysis indicated that the combined absence or presence of eaves , treated or untreated bed-nets , the number of house occupants , house size , netting over windows , and roof type were significantly related ( p < 0.05 ) to An.gambiae s.l . and An . funestus house entry in both villages . Conclusions Despite significant reductions in vector density and malaria transmission caused by high coverage of ITNs , high numbers of host-seeking malaria vectors are still found indoors due to house design s that favour mosquito entry . In addition to ITNs and IRS , significant efforts should focus on improving house design to prevent mosquito entry and eliminate indoor malaria transmission ABSTRACT Screening homes is an effective way of reducing house entry by mosquitoes . Here , we assess how important blocking the eaves is for reducing house entry by anopheline and culicine mosquitoes for houses that have screened doors and no windows . Twelve houses , with two screened doors and no windows , in which a single adult male slept , were included in a simple crossover design . In the first period , six houses were r and omly selected and had the eaves blocked using a mixture of rubble and mortar ; the other six were left with open eaves . Mosquitoes were sample d using CDC light traps from each house twice a week for 4 wk . Mosquito control activities and the number and type of domestic animals within the compound was recorded on each sampling occasion . Before beginning the second sampling period , homes with blocked eaves had them opened , and those with open eaves had them closed . Mosquitoes were then sample d from each house for a further 4 wk . When houses had their eaves closed , a three-fold reduction in Anopheles gambiae s.l . Giles caught indoors was observed . However , there was no reduction in total culicine numbers observed . This study demonstrates that the eaves are the major route by which An . gambiae enters houses . By contrast , culicine mosquitoes enter largely through doors and windows . Sealing the eave gap is an important method for reducing malaria transmission in homes where doors and windows are screened Recent research has indicated that the malaria burden in Asia may have been vastly underestimated . We conducted a prospect i ve community-based study in an impoverished urban site in Kolkata , India , to estimate the burden of malaria and typhoid fever and to identify risk factors for these diseases . In a population of 60452 people , 3605 fever episodes were detected over a 12-month period . The blood films of 93 febrile patients contained Plasmodium ( 90 P. vivax , 2 P. falciparum and 1 P. malariae ) . Blood cultures from 95 patients grew Salmonella enterica serotype Typhi . Malaria patients were found to be significantly older ( mean age 29 years ) compared with patients with typhoid fever ( 15 years ; P<0.001 ) but had similar clinical features on presentation . Having a household member with malaria , illiteracy , low household income and living in a structure not built of bricks were associated with an increased risk for malaria . Having a household member with typhoid fever and poor hygiene were associated with typhoid fever . A geographic analysis of the spatial distribution of malaria and typhoid fever cases detected high-risk neighbourhoods for each disease . Focal interventions to minimise human-vector contact and improved personal hygiene and targeted vaccination campaigns could help to prevent malaria and typhoid fever in this site BACKGROUND Plasmodium infections among school children in Igbo-Eze South Local Government of Enugu State , Nigeria , were studied between July and December 2005 . The relationship between the use of malaria control measures and the prevalence of Plasmodium infections was investigated . METHODS Blood smears were obtained from 1296 school children ( ages 4 - 15 years ) from six schools r and omly sample d from the study area . Drugs were given to infected children . Epidemiological question naires were administered to the children . RESULTS Out of 1296 school children examined , 270 ( 20.8 % ) had Plasmodium falciparum infections . The prevalence of these parasitic infections varied significantly ( p < 0.05 ) among schools , with Central School , Ovoko ( 30.1 % P falciparum ) and Community primary school , Itchi ( 13.9 % ) , having the highest and lowest prevalence rates respectively . Furthermore , the prevalence of P falciparum infections also varied significantly ( p < 0.05 ) among the age groups , with age groups 4 - 6 ( 35.1 % ) and 10 - 12 ( 14.2 % ) having the highest and lowest prevalence rates respectively . Males ( 23.1 % ) had a significantly higher prevalence rate than females ( 18.5 % ) . The prevalence of malaria was significantly lower among pupils using preventive measures ; 5.9 % among pupils using mosquito bed net as against 21.2 % among those not using bed nets and 4.6 % for pupils living in screened houses as against 24.1 % for those not living in screened houses . CONCLUSION The study revealed that malaria is a major public health problem among pupils in a Nigerian local community . Prevalence rates among pupils varied among location of schools , age and gender . Preventive measures favoured the use of bed nets and living in screened houses BACKGROUND Malaria has become one of the major health problems currently facing the urban communities . The rapid increase in urbanization , rural-urban migration and climatic changes are among the main factors contributing for the rise of malaria in urban areas . To our knowledge , there has been no malaria prevalence study so far conducted in Gondar Town . OBJECTIVE The aim of this study was to determine the prevalence of malaria infection and its associated risk factors in Gondar Town . METHODS A community-based survey was conducted in three r and omly selected malarious Kebeles of Gondar Town during November-December 2004 . Blood films were collected from a finger-prick of 734 members of the selected households for microscopic examination of malaria parasites . RESULTS Among 734 examined blood films , 39 ( 5.3 % ) were positive for malaria infection , of which 29 ( 74.4 % ) were due to Plasmodium falciparum and 10 ( 25.6 % ) due to P. vivax . Seven ( 18 % ) malaria infections were reported from children under the age of five years , indicating the endemicity of malaria to the study area . Age-specific rates show that higher malaria prevalence rate was found among under-five children ( 7.2 % ) and 15 - 19 year-old age group ( 7.3 % ) . Proximity to mosquito breeding sites was found to be the main risk factor for malaria infection ( OR = 2.4 , 95 % CI . 1.2 - 5.1 ) . CONCLUSIONS The prevalence of malaria in Gondar Town was found to be high . The prevalence was strongly associated with proximity of residence to potential mosquito breeding sites . The occurrence of the disease among under-five children would indicate that malaria is indigenous to the area . Use of personal protection methods such as insecticide treated mosquito nets should be scaled up , and malaria control interventions should target residents who are at a closer proximity to mosquito breeding sites Results of a prospect i ve study of the association between environmental factors and malaria occurrence among 1461 individuals in an Indian rural community are reported . A multiplicative model was fitted by relating malaria positivity with different environmental risk factors as categorical variables . The risk of acquiring malaria infections varied significantly within a village stratified by proximity of breeding sources to human dwellings ( chi 2 = 19.87 , df = 5 , p = 0.0000 ) and different types of houses ( chi 2 = 11.32 , df = 2 , p = 0.0035 ) . People residing in thatched houses with [ Relative Risk ( RR ) = 6.72 ] and without false ceiling ( RR = 11.27 ) are exposed to greater risk of contracting malaria infections when compared to tiled houses ( RR = 1.00 ) . However , malaria infection was not significantly associated with proximity of cattlesheds to human dwellings ( chi 2 = 1.54 , df = 2 , p = 0.46 ) . A significantly high risk was observed in zones where the cattle to man ratio was very low and vice versa ( chi 2 = 15.32 , df = 6 , p = 0.018 ) . These data suggest and corroborate with earlier studies that transmission is a local problem and it varies within a village according to the microepidemiological factors |
10,364 | 29,317,772 | Conclusions Our data demonstrate that increased tomato consumption is inversely associated with PCa risk .
These findings were accompanied with dose – response relationships for total tomato consumption and for cooked tomatoes and sauces . | Background Prostate cancer ( PCa ) is the second most frequently diagnosed cancer among men worldwide .
Many epidemiological studies have found an inverse association between increased tomato consumption and PCa risk .
This study aims to determine the associations between consumption of various types of tomato products and PCa risk and to investigate potential dose – response relationships . | The relationship between risk of prostate cancer and dietary intake of energy , fat , vitamin A , and other nutrients was investigated in a case-control study conducted in Ontario , Canada . Cases were men with a recent , histologically confirmed diagnosis of adenocarcinoma of the prostate notified to the Ontario Cancer Registry between April 1990 and April 1992 . Controls were selected r and omly from assessment lists maintained by the Ontario Ministry of Revenue , and were frequency-matched to the cases on age . The study included 207 cases ( 51.4 percent of those eligible ) and 207 controls ( 39.4 percent of those eligible ) , and information on dietary intake was collected from them by means of a quantitative diet history . There was a positive association between energy intake and risk of prostate cancer , such that men at the uppermost quartile level of energy intake had a 75 percent increase in risk . In contrast , there was no clear association between the non-energy effects of total fat and monounsaturated fat intake and prostate cancer risk . There was some evidence for an inverse association with saturated fat intake , although the dose-response pattern was irregular . There was a weak ( statistically nonsignificant ) positive association between polyunsaturated fat intake and risk of prostate cancer . Relatively high levels of retinol intake were associated with reduced risk , but there was essentially no association between dietary β-carotene intake and risk . There was no alteration in risk in association with dietary fiber , cholesterol , and vitamins C and E. Although these patterns were evident both overall and within age-strata , and persisted after adjustment for a number of potential confounding factors , they could reflect ( in particular ) the effect of nonrespondent bias The association between plasma carotenoids and prostate cancer risk was investigated in a case-control study nested within the prospect i ve Health Professionals Follow-up Study . We matched 450 incident prostate cancer cases diagnosed from 1993–1998 to 450 controls by age , time , month , and year of blood donation . Modest inverse , but not statistically significant , associations were observed among plasma α-carotene , β-carotene , and lycopene concentrations , and overall risk of prostate cancer diagnosis { odds ratio ( highest versus lowest quintile ; OR ) , α-carotene : OR , 0.67 [ 95 % confidence interval ( CI ) , −0.40–1.09 ] ; β-carotene : OR , 0.78 ( 95 % CI , 0.48–1.25 ) ; lycopene : OR , 0.66 ( 95 % CI , 0.38–1.13)}. The inverse association between plasma lycopene concentrations and prostate cancer risk was limited to participants who were 65 years or older ( OR , 0.47 ; 95 % CI , 0.23–0.98 ) and without a family history of prostate cancer ( OR , 0.48 ; 95 % CI , 0.26–0.89 ) . Combining , older age and a negative family history provided similar results ( OR , 0.43 ; 95 % CI , 0.18–1.02 ) . Inverse associations between β-carotene and prostate cancer risk were also found among younger participants ( < 65 years of age ; OR , 0.36 ; 95 % CI , 0.14–0.91 ; Ptrend = 0.03 ) . Combining dietary intake and plasma data confirmed our results . We found a statistically significant inverse association between higher plasma lycopene concentrations and lower risk of prostate cancer , which was restricted to older participants and those without a family history of prostate cancer . This observation suggests that tomato products may exhibit more potent protection against sporadic prostate cancer rather than those with a stronger familial or hereditary component . In addition , our findings also suggest that among younger men , diets rich in β-carotene may also play a protective role in prostate carcinogenesis BACKGROUND Several human studies have observed a direct association between retinol ( vitamin A ) intake and risk of prostate cancer ; other studies have found either an inverse association or no association of intake of beta-carotene ( the major provitamin A ) with risk of prostate cancer . Data regarding carotenoids other than beta-carotene in relation to prostate cancer risk are sparse . PURPOSE We concluded a prospect i ve cohort study to examine the relationship between the intake of various carotenoids , retinol , fruits , and vegetables and the risk of prostate cancer . METHODS Using responses to a vali date d , semiquantitative food-frequency question naire mailed to participants in the Health Professionals Follow-up Study in 1986 , we assessed dietary intake for a 1-year period for a cohort of 47,894 eligible subjects initially free of diagnosed cancer . Follow-up question naires were sent to the entire cohort in 1988 , 1990 , and 1992 . We calculated the relative risk ( RR ) for each of the upper categories of intake of a specific food or nutrient by dividing the incidence rate of prostate cancer among men in each of these categories by the rate among men in the lowest intake level . All P values result ed from two-sided tests . RESULTS Between 1986 and 1992 , 812 new cases of prostate cancer , including 773 non-stage A1 cases , were documented . Intakes of the carotenoids beta-carotene , alpha-carotene , lutein , and beta-cryptoxanthin were not associated with risk of non-stage A1 prostate cancer ; only lycopene intake was related to lower risk ( age- and energy-adjusted RR = 0.79 ; 95 % confidence interval [ CI ] = 0.64 - 0.99 for high versus low quintile of intake ; P for trend = .04 ) . Of 46 vegetables and fruits or related products , four were significantly associated with lower prostate cancer risk ; of the four -- tomato sauce ( P for trend = .001 ) , tomatoes ( P for trend = .03 ) , and pizza ( P for trend = .05 ) , but not strawberries -- were primary sources of lycopene . Combined intake of tomatoes , tomato sauce , tomato juice , and pizza ( which accounted for 82 % of lycopene intake ) was inversely associated with risk of prostate cancer ( multivariate RR = 0.65 ; 95 % CI = 0.44 - 0.95 , for consumption frequency greater than 10 versus less than 1.5 servings per week ; P for trend = .01 ) and advanced ( stages C and D ) prostate cancers ( multivariate RR = 0.47 ; 95 % CI = 0.22 - 1.00 ; P for trend = .03 ) . No consistent association was observed for dietary retinol and risk of prostate cancer . CONCLUSIONS These findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk , but other measured carotenoids are unrelated to risk . IMPLICATION S Our findings support recommendations to increase vegetable and fruit consumption to reduce cancer incidence but suggest that tomato-based foods may be especially beneficial regarding prostate cancer risk In order to learn about the influence of dietary factors and obesity on prostatic cancer in our environment , a case-control study was performed . The group of cases consisted of 90 men histologically diagnosed with prostatic cancer in the ' La Paz ' hospital ( Madrid ) during the 4-year period of 1983 - 1987 . The controls were 180 men selected to obtain a r and om sample of males from the same hospital , stratified according to age and date of admission as compared with the prostatic cancer patients . The results of the study revealed that a diet rich in animal fats as well as high in meat consumption increased the risk of prostatic cancer . Low ingestion of vitamin A or vitamin C and obesity were unassociated to the disease Previously , tomato powder ( TP ) diets initiated postweaning have been shown to be effective in reducing prostate cancer in the transgenic adenocarcinoma of the mouse prostate ( TRAMP ) model . The TRAMP model develops and progresses through all stages of carcinogenesis similarly to humans . We hypothesized that a 10 % TP diet intervention after puberty would reduce carcinogenesis at 12 , 16 , and 20 weeks of age in TRAMP mice . Eight-week-old male C57BL/6 X FVB F1 TRAMP mice were r and omized to consume either an AIN-93 G + 10 % TP diet ( n = 90 ) or the AIN-93 G control diet ( n = 88 ) and r and omized to 1 of 3 end point ages : 12 ( n = 59 ) , 16 ( n = 60 ) , or 20 ( n = 59 ) weeks of age . There was no difference between diets in overall cancer incidence at any time point . However , at 16 weeks of age , TP significantly increased high- grade PIN ( P = .014 ) and significantly decreased poorly differentiated ( P = .024 ) lesions compared with the control diet suggesting a delay in the progression of prostate cancer . Two variables that may explain the modest effect of TP in this study are as follows : the low amount of lycopene in the TP diet ( 12.3 ppm ) and the timing of the intervention ( 8 weeks of age ) . The TP diet contained 30-fold less lycopene than previous studies in our laboratory . In addition , the initiation of the diet intervention time of 8 weeks of age instead of 4 weeks of age may have been too late in cancer progression to substantially impact carcinogenesis . In conclusion , a low-lycopene TP intervention failed to reduce carcinogenesis in TRAMP mice BACKGROUND The amount of dietary fat required for optimal bioavailability of carotenoids in plant matrices is not clearly defined . OBJECTIVE The objective was to quantify the appearance of carotenoids in plasma chylomicrons after subjects ingested fresh vegetable salads with fat-free , reduced-fat , or full-fat salad dressings . DESIGN The subjects ( n = 7 ) each consumed 3 salads consisting of equivalent amounts of spinach , romaine lettuce , cherry tomatoes , and carrots with salad dressings containing 0 , 6 , or 28 g canola oil . The salads were consumed in r and om order separated by washout periods of > or = 2 wk . Blood sample s were collected hourly from 0 to 12 h. Chylomicrons were isolated by ultracentrifugation , and carotenoid absorption was analyzed by HPLC with coulometric array detection . RESULTS After ingestion of the salads with fat-free salad dressing , the appearance of alpha-carotene , beta-carotene , and lycopene in chylomicrons was negligible . After ingestion of the salads with reduced-fat salad dressing , the appearance of the carotenoids in plasma chylomicrons increased relative to that after ingestion of the salads with fat-free salad dressing ( P < 0.04 ) . Similarly , the appearance of the carotenoids in plasma chylomicrons was higher after the ingestion of salads with full-fat than with reduced-fat salad dressing ( P < 0.02 ) . CONCLUSIONS High-sensitivity HPLC with coulometric array detection enabled us to quantify the intestinal absorption of carotenoids ingested from a single vegetable salad . Essentially no absorption of carotenoids was observed when salads with fat-free salad dressing were consumed . A substantially greater absorption of carotenoids was observed when salads were consumed with full-fat than with reduced-fat salad dressing BACKGROUND There is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer , the identification of which may improve prevention . Given their antioxidant properties , we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion transmembrane protease , serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog ( ERG ) . OBJECTIVE We aim ed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype . DESIGN Our study population consisted of a prospect i ve cohort of 46,719 men from the Health Professionals Follow-Up Study . TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens . We used multivariable competing risk models to calculate HRs and 95 % CIs for the risk of ERG-positive and , separately , ERG-negative disease . We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases . RESULTS During 23 y of follow-up , 5543 men were diagnosed with prostate cancer , among whom 884 were assayed for ERG ( 426 ERG-positive ) . With inclusion of only the latter cases , increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall ( ≥2 servings/wk compared with < 1 serving/mo ; multivariable HR : 0.70 ; 95 % CI : 0.52 , 0.95 ; P-trend = 0.002 ) . With respect to molecular subtypes , cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease ( HR : 0.54 ; 95 % CI : 0.37 , 0.81 ; P-trend = 0.004 ) but not with ERG-negative disease ( HR : 0.96 ; 95 % CI : 0.62 , 1.50 ; P-trend = 0.10 ) ( P-heterogeneity = 0.04 ) . Increasing quintiles of lycopene intake were associated with a decreased risk of both subtypes ( P-heterogeneity = 0.79 ) . Inverse probability weighting did not material ly change the results . CONCLUSIONS Our results lend some support to the hypothesis that prostate cancers that harbor TMPRSS2:ERG may be etiologically distinct from fusion-negative cancers . In particular , tomato sauce consumption may play a role in reducing TMPRSS2:ERG-positive disease Background : Relationships between fruit , vegetable , and mature bean consumption and prostate cancer risk are unclear . Methods : We examined associations between fruit and vegetable groups , specific fruits and vegetables , and mature bean consumption and prostate cancer risk overall , by stage and grade , and for prostate cancer mortality in a pooled analysis of 15 prospect i ve cohorts , including 52,680 total cases and 3,205 prostate cancer – related deaths among 842,149 men . Diet was measured by a food frequency question naire or similar instrument at baseline . We calculated study -specific relative risks using Cox proportional hazards regression , and then pooled these estimates using a r and om effects model . Results : We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group ( including total fruits and vegetables , total fruits , total vegetables , fruit and vegetable juice , cruciferous vegetables , and tomato products ) , nor specific fruit and vegetables . In addition , we observed few statistically significant results for other prostate cancer outcomes . Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09 . There was no evidence of effect modification for any association by age or body mass index . Conclusions : Results from this large , international , pooled analysis do not support a strong role of collective groupings of fruits , vegetables , or mature beans in prostate cancer . Impact : Further investigation of other dietary exposures , especially indicators of bioavailable nutrient intake or specific phytochemicals , should be considered for prostate cancer risk . Cancer Epidemiol Biomarkers Prev ; 26(8 ) ; 1276–87 . © 2017 AACR Cruciferous vegetables , tomato sauce and legumes have been associated with reduced risk of incident advanced prostate cancer . In vitro and animal studies suggest these foods may inhibit progression of prostate cancer , but there are limited data in men . Therefore , we prospect ively examined whether intake of total vegetables , and specifically cruciferous vegetables , tomato sauce and legumes , after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor , a United States prostate cancer registry . As a secondary analysis , we also examined other vegetable subgroups , total fruit and subgroups of fruits . The participants were diagnosed primarily at community-based clinics and followed from 2004 to 2009 . We assessed vegetable and fruit intake via a semi-quantitative food frequency question naire , and ascertained prostate cancer outcomes via urologist report and medical records . We observed 134 events of progression ( 53 biochemical recurrences , 71 secondary treatments likely due to recurrence , 6 bone metastases and 4 prostate cancer deaths ) during 3,171 person-years . Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59 % decreased risk of prostate cancer progression compared to men in the lowest quartile ( hazard ratio ( HR ) : 0.41 ; 95 % confidence interval ( CI ) : 0.22 , 0.76 ; p-trend : 0.003 ) . No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression . In conclusion , cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression Lycopene is present mainly as cis-isomers in human serum and tissues whereas all-trans-lycopene predominates in tomato products , suggesting that all-trans-lycopene is isomerised in the body or is less bioavailable . The objectives of the present study were to develop processing conditions for tomatoes to obtain products with different cis-trans-lycopene isomer distribution and to assess their bioavailability . Healthy adult subjects ( n 12 ) were recruited for this r and omised cross-over trial . Each intervention was preceded by a 2-week washout period . Two tomato sauces , one rich in all-trans-lycopene ( 32.5 mg total lycopene/100 g sauce ; 5 % cis-isomers ) , the other high in cis-lycopene ( 26.4 mg total lycopene/100 g sauce ; 45 % cis-isomers ) , were produced by different heat-processing techniques . Each sauce ( 150 g ) was served in a st and ardised meal at 08.00 hours after overnight fasting . Plasma TAG-rich lipoprotein fractions over 9.5 h following test-meal consumption as a measure of lycopene absorption were obtained and expressed as baseline-corrected area under the concentration v. time curves ( AUC ) , using HPLC-electrochemical detection . AUC values adjusted for the amount lycopene consumed showed that total , total cis- , and all-trans-lycopene responses were significantly higher from the cis-isomer-rich sauce , compared with the all-trans-rich sauce , being 7.30 ( sem 1.45 ) v. 4.74 ( sem 1.08 ) nmol x h/l ( P = 0.002 ) , 3.80 ( sem 0.76 ) v. 1.98 ( sem 0.37 ) nmol x h/l ( P = 0.0005 ) and 3.50 ( sem 0.76 ) v. 2.76 ( sem 0.76 ) nmol x h/l ( P = 0.01 ) , respectively . The present study demonstrates significant lycopene bioavailability from cis-lycopene-rich tomato sauce and highlights the importance of considering isomer-distribution for lycopene bioavailability . Furthermore , processing parameters can be controlled to alter isomer patterns of tomato products and influence lycopene bioavailability BACKGROUND Prostate cancer is a disease with a complex etiology . Oxidative stress has been implicated in its pathogenesis ; however , few prospect i ve studies have investigated the association between an oxidative stress/balance score and risk of prostate cancer . METHODS We investigated associations between an oxidative balance score , calculated as the summation of individual scores obtained from five pro-oxidative and eight anti-oxidative exposures , as well as each individual constituent of the score and risks of prostate cancer overall , and by clinical characteristics , in a case-cohort study ( 661 cases and 1864 subcohort ) nested within the Canadian Study of Diet , Lifestyle , and Health cohort . Men in the lowest quintiles of each pro-oxidant exposure received a score of four ( the highest score ) , while those in the highest quintile received a score of zero ( the lowest score ) . In contrast , scoring for all anti-oxidants was performed in the opposite way . Total oxidative balance score was calculated by summating all individual scores of pro- and anti-oxidative variables , with higher values indicating a higher antioxidant status . RESULTS The average oxidative balance score was similar between prostate cancer cases and men in the subcohort : 25.2 and 25.3 , respectively . There was no association between oxidative balance score and overall risk of prostate cancer with hazard ratios ( HRs ) of 1.00 , 1.02 , 1.03 , 0.97 and 1.01 for increasing quintiles of the score ( p-trend=0.71 ) . There were also no associations for non-advanced or advanced disease , or when analysis was restricted to incident cases that arose after two years of follow-up ( n=508 ) . In general constituents of the score were not associated with prostate cancer , except for red meat intake ( HR=1.44 ; 95%CI 1.06 - 1.95 comparing Q5 vs. Q1 ) and lycopene ( HRs of 0.7 - 0.8 for increasing quintiles ) . CONCLUSION Our findings do not support an association between oxidative balance score and risks of overall prostate cancer or advanced disease The relationship between the risk of prostate cancer and dietary intake of energy , fat , vitamin A , and other nutrients was investigated in a case-control study conducted in Montreal ( Quebec ) , Canada . French Canadians aged 35 to 84 years with a recent , histologically confirmed diagnosis of adenocarcinoma of the prostate were identified through the admission offices of five major francophone teaching-hospitals in Montreal from 1989 to 1993 . Population -based controls matched for age ( ±five years ) , language , and place of residence were selected by a modified r and om-digit dialing method . The study included 232 cases and 231 controls . Information on dietary intake was collected by means of a quantitative dietary history . No association was evident between energy intake and the risk of prostate cancer . In contrast , there was some evidence of an inverse association with intake of total fat , animal fat , monounsaturated fat , and particularly saturated fat ( odds ratio = 0.69 , 95 percent confidence interval = 0.40–1.18 , P=0.05 ) , while a nonsignificant positive association was found with polyunsaturated fat . In addition , high intake of retinol and vegetable protein ( highest cf lowest quartile ) was associated with reduced risk , but was not statistically significant . No associations were established between intake of other nutrients and risk . These patterns persisted after adjustment for a number of potential confounding factors Objective : To examine the risk of prostate cancer associated with foods and nutrients , including individual fatty acids and carotenoids . Methods : Population -based case – control study of 858 men aged < 70 years at diagnosis with histologically confirmed prostate cancer of Gleason Grade 5 or greater , and 905 age-frequency-matched men , selected at r and om from the electoral rolls . Dietary intakes were assessed with a 121-item food frequency question naire . Results : Inverse associations with prostate cancer were observed for ( Odds ratio , OR , 95 % confidence intervals , 95 % CI for tertile III compared with tertile I ) allium vegetables 0.7 , 0.5–0.9 ; p trend 0.01 , tomato-based foods 0.8 , 0.6–1.0 ; p trend 0.03 and total vegetables 0.7 , 0.5–1.0 ; p trend 0.04 . Margarine intake was positively associated with prostate cancer 1.3 , 1.0–1.7 ; p trend 0.04 . The only statistically significant associations observed with nutrients were weak inverse associations for palmitoleic acid ( p trend 0.04 ) , fatty acid 17:1 ( p trend 0.04 ) , and 20:5 n-6 ( p trend 0.05 ) ; and a non-significant trend for oleic acid ( p trend 0.09 ) . Neither total , nor beverage-specific , intake of alcohol was associated with risk . Conclusions : Based on these findings , diets rich in olive oil ( a source of oleic acid ) , tomatoes and allium vegetables might reduce the risk of prostate cancer Tomatoes may have beneficial effects on prostate health . Efficacy trials would require long-term adherence to high levels of tomato product ( TP ) consumption . Therefore , factors that affect adherence in men most at risk and whether increased consumption of TP negatively affects diet and health are important concerns . Cancer-free African – American ( AA ) men ( n 36 ) with mean serum prostate-specific antigen of 7.4 SD 5.6 ) ng/ml were r and omised to consume one serving of TP/d or a control diet for 3 months . Mean intervention group lycopene intake rose to 464 % , with negligible control group increase . Plasma lycopene levels rose by 53 and 40 % in the intervention group in months 1 and 3 , respectively ( P < 0.0001 ) , with no control group change . The intervention group ’s barriers to adherence score was inversely associated with both dietary ( r -0.49 , P = 0.02 ) and plasma lycopene concentration ( r -0.37 , P = 0.02 ) . Their TP disadvantage score negatively correlated with the 3-month plasma lycopene concentrations ( r -0.37 , P = 0.008 ) and their weekly incentives and impediments were remarkably stable , ‘ concern for prostate health ’ being the most consistent over time . ‘ Liking tomatoes ’ and ‘ study participation ’ decreased in citation frequency at weeks 6 and 9 , respectively . No major shifts occurred in dietary cholesterol or saturated fat , with no adverse effects on gastrointestinal complaints , serum total cholesterol , body weight or blood pressure . Lower socio-economic status AA men at higher prostate cancer risk can successfully achieve a whole food intervention goal with a corresponding rise in plasma lycopene concentrations , with no adverse effects on self-selected diet quality or health parameters BACKGROUND Individual studies have suggested that circulating carotenoids , retinol , or tocopherols may be associated with prostate cancer risk , but the studies have not been large enough to provide precise estimates of associations , particularly by stage and grade of disease . OBJECTIVE The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids , retinol , α-tocopherol , and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors . DESIGN Principal investigators of prospect i ve studies provided individual participant data for prostate cancer cases and controls . Risk by study -specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets . RESULTS Data were available for up to 11,239 cases ( including 1654 advanced stage and 1741 aggressive ) and 18,541 controls from 15 studies . Lycopene was not associated with overall risk of prostate cancer , but there was statistically significant heterogeneity by stage of disease , and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 ( 95 % CI : 0.46 , 0.91 ; P-trend = 0.032 ) . No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease . For retinol , the OR for the highest compared with the lowest fifth was 1.13 ( 95 % CI : 1.04 , 1.22 ; P-trend = 0.015 ) . For α-tocopherol , the OR for the highest compared with the lowest fifth was 0.86 ( 95 % CI : 0.78 , 0.94 ; P-trend < 0.001 ) , with significant heterogeneity by stage of disease ; the OR for aggressive prostate cancer was 0.74 ( 95 % CI : 0.59 , 0.92 ; P-trend = 0.001 ) . γ-Tocopherol was not associated with risk . CONCLUSIONS Overall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol , and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol . Whether these associations reflect causal relations is unclear Epidemiological data on most cancer sites suggest that consumption of plant foods , which contain high levels of antioxidants , might slow or prevent the appearance of cancer . We used data from three case-control studies to test this hypothesis . The total study population consisted of 617 incident cases of prostate cancer and 636 population controls from Ontario , Quebec , and British Columbia . Dietary information was collected by an in-person interview with a detailed quantitative dietary history . Unconditional logistic regression analyses were performed to estimate odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . A decreasing , statistically significant association was found with increasing intakes of green vegetables ( OR = 0.54 , 95 % CI = 0.40 - 0.71 for 4th quartile ) , tomatoes ( OR = 0.64 , 95 % CI = 0.45 - 0.91 ) , beans/lentils/nuts ( OR = 0.69 , 95 % CI = 0.53 - 0.91 ) , and cruciferous vegetables ( OR = 0.69 , 95 % CI = 0.52 - 0.91 for 3rd quartile ) . Higher intakes of fruit were associated with higher ORs ( OR = 1.51 , 95 % CI = 1.14 - 2.01 for 4th quartile ) , an effect that was seen for total fruit and citrus fruit , as well as for all other noncitrus fruits . Among the grains , refined-grain bread intake was associated with a decrease in risk ( OR = 0.65 for 4th quartile ) , whereas whole-grain breakfast cereals were associated with a higher risk for prostate cancer . Of all the antioxidant nutrients studied , the ORs were higher with higher intakes of cryptoxanthin ( OR = 1.44 , 95 % CI = 1.09 - 1.89 for 4th quartile ) . Exposure to certain dietary components of plant origin , which are potentially modifiable , indicates the theoretical scope for reducing the risk from prostate cancer . Future experimental studies or trials are warranted for further underst and ing The association between diet and prostate cancer ( PC ) risk , although suggestive , still remains largely elusive particularly in the Asian population . This study sought to further evaluate the possible effects of different dietary factors on risk of PC in Iran . Using data from a prospect i ve hospital-based multicenter case-control study , dietary intakes of red meat , fat , garlic , and tomato/tomato products , as well as thorough demographic and medical characteristics , were determined in 194 cases with the newly diagnosed , clinicopathologically confirmed PC and 317 controls , without any malignant disease , admitted to the same network of hospitals . Odds ratios ( ORs ) and corresponding 95 % confidence intervals ( CIs ) were obtained after adjustment for major potential confounders , including age , body mass index , smoking , alcohol , education , occupation , family history of PC , and total dietary calories . Comparing the highest with the lowest tertile , a significant trend of increasing risk with more frequent consumption was found for dietary fat ( OR : 1.79 , 95 % CI : 1.71–4.51 ) , whereas inverse association was observed for tomato/tomato products ( OR : 0.33 , 95 % CI : 0.16–0.65 ) . A nonsignificant increase in PC risk was revealed for dietary red meat ( OR : 1.69 , 95 % CI : 0.93–3.06 ) . For garlic consumption , a borderline reduction in risk was observed ( OR : 0.58 , 95 % CI : 0.32–1.01 ; P = 0.05 ) . In conclusion , our study supports the hypothesis that total fat may increase PC risk and tomatoes/tomato products and garlic may protect patients against PC Objectives We examined post-diagnostic diet and risk of cancer progression in a cohort of men with prostate cancer from the Health Professionals Follow-up Study . Methods We observed 392 progression outcomes among 1,202 men diagnosed with incident localized/regional prostate cancer between 1986 and 1996 . Men completed prospect i ve dietary surveys before and after diagnosis and were followed through 2000 . We examined post-diagnostic consumption of red meat , grains , vegetables , fruits , milk , tomatoes , tomato sauce , and fish as predictors of progression using Cox proportional hazard regression models adjusted for total energy , age , clinical factors , and pre-diagnostic diet . Results Men in the highest versus lowest quartile of post-diagnostic fish consumption had a multivariate hazard ratio ( HR ) of progression of 0.73 ( 95 % CI 0.52–1.02 ) ; the comparable HR for tomato sauce was 0.56 ( 95 % CI 0.38–0.82 ) . We observed inverse linear relationships for fish and tomato sauce and risk of progression ( HR = 0.83 , p-value = 0.006 and HR = 0.80 , p-value = 0.04 for a two serving/week increase of fish and tomato sauce , respectively ) . Milk and fresh tomato consumption were associated with small elevations in risk . Conclusions These data suggest that diet after diagnosis may influence the clinical course of prostate cancer , and fish and tomato sauce may offer some protection against disease progression The role of diet in the etiology of prostate cancer remains unclear , because results from several case‐control and cohort studies on fat intake and risk of prostate cancer have been inconsistent ; few of the studies have adjusted the results for caloric intake . To examine the relationship between energy , intake of several nutrients and risk of prostate cancer ( all stages combined and advanced stages separately ) , we conducted a population ‐based case‐control study in Örebro County , Sweden , from 1989 through 1994 . A total of 526 patients with newly diagnosed prostate cancer and 536 controls , r and omly selected from the population register and frequency‐matched by age , were included in the analyses . Information about dietary intake was obtained from a self‐administered semi‐quantitative food frequency question naire . Odds ratios with 95 % confidence intervals were estimated by unconditional logistic regression . In age‐adjusted analyses , there were positive associations of prostate cancer ( all stages combined ) risk with total energy intake as well as intake of total fat ( saturated and monounsaturated ) , protein , retinol and zinc . The positive association with energy intake was stronger for advanced cancer , with an excess risk of 70 % for the highest quartile vs. the lowest . After adjustment for energy intake , there was no apparent association of prostate cancers ( all stages combined ) with any of the investigated nutrients . However , a weak positive association between intake of retinol and advanced cancer was observed . We conclude that our results provide some evidence that total energy intake is a risk factor for prostate cancer . © 1996 Wiley‐Liss , Tomato products , good sources of lycopene , may lower the incidence of prostate cancer , but data on the effectiveness of lycopene supplementation during radiation therapy are lacking . This study aim ed to evaluate the tolerance and acceptance of three different amounts ( 4 , 8 , or 12 oz ) of tomato juice ( TJ ) and their effect on serum lycopene during radiotherapy in 20 men with localized prostate cancer . Participants were r and omized into a control group or one of three intervention groups who consumed TJ daily during treatment . Dietary lycopene intake was estimated using the National Cancer Institute ( NCI ) Diet History Question naire , and gastrointestinal tolerance of TJ was evaluated using the NCI Cancer Therapy Evaluation Program : Common Toxicity Criteria v 2.0 . Serum and TJ lycopene levels were measured by liquid chromatography-mass spectrometry . TJ was well tolerated without any gastrointestinal side effects , and increased serum lycopene levels were observed in the 8 and 12 oz groups from baseline to endpoint . No correlation between serum and dietary lycopene was detected . Despite no reported change in dietary intake , non-significant weight loss was observed in the control group but not the intervention group participants . A significant positive correlation between serum lycopene , weight , and body mass index , and a negative correlation between serum lycopene and piror nutritional supplement use was detected . Weight change should be monitored and evaluated during treatment . Larger clinical trials are needed to vali date the use of TJ to increase serum/dietary lycopene intake and correlate with side effects during radiotherapy in men with prostate cancer Although dietary risk factors may differ between localized and advanced prostate cancer , data on associations between the consumption of fruits and vegetables and risk of localized and advanced cancers are limited . We examined associations between fruit and vegetable consumption and risk of prostate cancer in a Japanese population . During 1995–1998 , a vali date d food frequency question naire was administered to 43,475 men aged 45–74 yr . During 321,061 person-years of follow-up until the end of 2004 , 339 cases of prostate cancer were identified . Consumption of fruits or total vegetables was not associated with a decreased risk of total prostate cancer , with corresponding multivariate hazard ratios of the highest vs. lowest quartiles of 1.09 ( 95 % CI = 0.77–1.53 ; trend P = 0.39 ) for fruits and 1.33 ( 95 % CI = 0.93–1.91 ; trend P = 0.52 ) for total vegetables . Also , no association was observed for intake of either fruits or vegetables ( total or any subtype ) with localized or advanced prostate cancer . This prospect i ve cohort study suggests that consumption of fruits or vegetables may not be associated with the risk of either localized or advanced prostate cancer in Japanese men . However , the possibility of confounding by detection bias on the risk of localized cancer could not be totally ruled out Although experimental studies suggest that fruits , vegetables and legumes may exert protective effects against prostate carcinogenesis through various bioactive compounds such as dietary fibre and antioxidants , epidemiological evidence is lacking . Notably , very few prospect i ve studies have investigated the relationship between legume intake and prostate cancer risk . Our objective was to prospect ively investigate the association between fruit , vegetable , tomato products , potatoes and legume intakes and prostate cancer risk . This study included 3313 male participants to the SUpplémentation en VItamines et Minéraux AntioXydants cohort ( follow-up : 1994 - 2007 ) who completed at least three 24-h dietary records during the first 2 years of follow-up . Associations between tertiles of intake and prostate cancer risk were assessed by multivariate Cox proportional hazards models . After a median follow-up of 12·6 years , 139 incident prostate cancers were diagnosed . An inverse association was observed between prostate cancer risk and tertiles of legume intake ( hazard ratio (HR)T3v . T1=0·53 ; 95 % CI 0·34 , 0·85 ; P trend=0·009 ) . This association was maintained after excluding soya and soya products from the legume group ( HRT3 v . T1=0·56 ; 95 % CI 0·35 , 0·89 ; P trend=0·02 ) . No association was observed between prostate cancer risk and tertiles of intakes of fruits ( P trend=0·25 ) , vegetables ( P trend=0·91 ) , potatoes ( P trend=0·77 ) and tomato products ( P trend=0·09 ) . This prospect i ve study confirms the null association between fruit and non-starchy vegetable intakes and prostate cancer risk observed in most previous cohorts . In contrast , although very few prospect i ve studies have been published on the topic , our results suggest an inverse association between legume intake and prostate cancer risk , supported by mechanistic plausibility . These results should be confirmed by large-scale observational and intervention studies BACKGROUND The rate of decrease in advanced cancers is an estimate for determining prostate cancer ( PCa ) screening program effectiveness . OBJECTIVE Assess the effectiveness of PCa screening programs using a 2- or 4-yr screening interval . DESIGN , SETTING , AND PARTICIPANTS Men aged 55 - 64 yr were participants at two centers of the European R and omized Study of Screening for Prostate Cancer : Gothenburg , Sweden ( 2-yr screening interval , n=4202 ) , and Rotterdam , the Netherl and s ( 4-yr screening interval , n=13 301 ) . We followed participants until the date of PCa , the date of death , or the last follow-up at December 31 , 2008 , or up to a maximum of 12 yr after initial screening . Potentially life-threatening ( advanced ) cancer was defined as cancer with at least one of following characteristics : clinical stage ≥T3a , M1 , or N1 ; serum prostate-specific antigen ( PSA ) > 20.0 ng/ml ; or Gleason score ≥8 at biopsy . INTERVENTION We compared the proportional total ( advanced ) cancer incidence ( screen-detected and interval cases ) , defined as the ratio of the observed number of ( advanced ) cancers to the expected numbers of ( advanced ) cancers based on the control arm of the study . MEASUREMENTS The proportional cancer incidence from the second screening round until the end of observation was compared using a 2- or 4-yr screening interval . RESULTS AND LIMITATIONS From screening round 2 until the end of observation , the proportional cancer incidence was 3.64 in Gothenburg and 3.08 in Rotterdam ( relative risk [ RR ] : 1.18 ; 95 % confidence interval [ CI ] , 1.04 - 1.33 ; p=0.009 ) . The proportional advanced cancer incidence was 0.40 in Gothenburg and 0.69 in Rotterdam ( RR : 0.57 ; 95 % CI , 0.33 - 0.99 ; p=0.048 ) ; the RR for detection of low-risk PCa was 1.46 ( 95 % CI , 1.25 - 1.71 ; p<0.001 ) . This study was limited by the assumption that PSA testing in the control arm was similar in both centers . CONCLUSIONS A 2-yr screening interval significantly reduced the incidence of advanced PCa ; however , the 2-yr interval increased the overall risk of being diagnosed with ( low-risk ) PCa compared with a 4-yr interval in men aged 55 - 64 yr . Individualized screening algorithms must be improved to provide the strategy for this issue UNLABELLED We present the main findings observed to date from the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) on dietary factors associated with the most frequent cancer sites . METHODS EPIC is a multicentre prospect i ve study carried out in 23 centres in 10 European countries : Denmark , France , Germany , Greece , Italy , the Netherl and s , Norway , Spain , Sweden and the United Kingdom , including 519,978 participants ( 366,521 women and 153,457 men ) , most aged 35 - 70 years . RESULTS We observed the following significant associations : gastric cancer risk was inversely associated with high plasma vitamin C , some carotenoids , retinol and α-tocopherol , high intake of cereal fibre and high adhesion to Mediterranean diet , while red and processed meat were associated with increased risk . High intake of dietary fibre , fish , calcium , and plasma vitamin D were associated with a decreased risk of colorectal cancer , while red and processed meat intake , alcohol intake , body mass index ( BMI ) and abdominal obesity were associated with an increased risk . High intake of fruit and vegetables in current smokers were associated with a decreased risk of lung cancer . An increased risk of breast cancer was associated with high saturated fat intake and alcohol intake . In postmenopausal women , BMI was positively and physical activity negatively associated with breast cancer risk . High intake of dairy protein and calcium from dairy products and high serum concentration of IGF-I were associated with an increased risk of prostate cancer . These results contribute to scientific evidence for appropriate public health strategies and prevention activities aim ed at reducing the global cancer burden |
10,365 | 29,426,587 | In general , both transcutaneous electrical nerve stimulation and interferential current improved pain and functional outcomes without a statistical difference between them . | BACKGROUND Transcutaneous electrical nerve stimulation and interferential current have been widely used in clinical practice .
However , a systematic review comparing their effects on pain relief has not yet been performed .
OBJECTIVES To investigate the effects of transcutaneous electrical nerve stimulation and interferential current on acute and chronic pain . | BACKGROUND Recent studies have shown that a transcutaneous electrical nerve stimulation ( TENS ) and interferential current ( IFC ) application reduces pain in subjects with musculoskeletal disorders . However there are no clinical trials evaluating or comparing the muscle relaxation generated for these devices . PURPOSE To compare the muscle relaxation of the upper trapezius induced by the application of TENS and IFC in females with chronic nonspecific neck discomfort . METHODS Sixty-four females between 18 and 40 years of age and a history of nonspecific neck discomfort were r and omly assigned to a TENS or an IFC group . The women in the TENS ( N = 32 ; mean age 22 years ) and IFC ( N = 32 , mean age 23 years ) group were su bmi tted to current application during 3 consecutive days and were assessed by electromyography ( EMG ) in different times aim ing to quantify the muscular tension of the upper trapezius . A visual analogue scale ( VAS ) was used as pain measure at baseline ( before TENS or IFC application ) and at the end of the study . RESULTS At baseline , demographic , pain , and EMG assessment data were similar between groups . Those in the IFC group had a significant trapezius relaxation after 3 IFC applications when compared to baseline and intermediate evaluations ( P < 0.05 ) . In contrast , the same analysis showed no significant difference between all assessment s in the TENS group ( P > 0.05 ) . In relation to pain relief , both groups showed an improvement at the end of the study when compared to baseline ( both , P < 0.05 ) . The between-group analysis showed no difference for the subjects who received such IFC as TENS application ( P < 0.05 ) . CONCLUSION IFC induced the upper trapezius relaxation after 3 sessions in females with neck discomfort , but the TENS application did not change the muscular tension . However , these results should be carefully interpreted due to the lack of differences between groups . A significant pain decrease was found in the subjects of both groups , however , only the IFC application presented a clinical ly important improvement OBJECTIVE To compare the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , interferential currents ( IFCs ) , and shortwave diathermy ( SWD ) against each other and sham intervention with exercise training and education as a multimodal package . DESIGN A double-blind , r and omized , controlled , multicenter trial . SETTING Departments of physical medicine and rehabilitation in 4 centers . PARTICIPANTS Patients ( N=203 ) with knee osteoarthritis ( OA ) . INTERVENTIONS The patients were r and omized by the principal center into the following 6 treatment groups : TENS sham , TENS , IFCs sham , IFCs , SWD sham , and SWD . All interventions were applied 5 times a week for 3 weeks . In addition , exercises and an education program were given . The exercises were carried out as part of a home-based training program after 3 weeks ' supervised group exercise . MAIN OUTCOME MEASURES Primary outcome was a visual analog scale ( 0 - 100 mm ) to assess knee pain . Other outcome measures were time to walk a distance of 15 m , range of motion , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , Nottingham Health Profile , and paracetamol intake ( in grams ) . RESULTS We found a significant decrease in all assessment parameters ( P<.05 ) , without a significant difference among the groups except WOMAC stiffness score and range of motion . However , the intake of paracetamol was significantly lower in each treatment group when compared with the sham groups at 3 months ( P<.05 ) . Also , the patients in the IFCs group used a lower amount of paracetamol at 6 months ( P<.05 ) in comparison with the IFCs sham group . CONCLUSIONS Although all groups showed significant improvements , we can suggest that the use of physical therapy agents in knee OA provided additional benefits in improving pain because paracetamol intake was significantly higher in the patients who were treated with 3 sham interventions in addition to exercise and education Objectives . Newly developed bidirectional modulated sine waves ( BMW ) might provide some derived benefit to patients with low back pain . Pain relief by transcutaneous electric nerve stimulation ( TENS ) with BMWs was tested . Material s and Methods . Analgesic effects of BMWs and conventional bidirectional pulsed waves on chronic back pain in 28 patients were compared , and effects of repeated TENS using BMWs on chronic back pain were investigated in 21 patients by means of a r and omized double-blind , sham-controlled , parallel-group method . Pain intensity was assessed using numerical rating scale ( NRS ) . Results . There was significant immediate reduction in NRS in patients receiving BMWs , and 60 min after treatment compared to sham TENS . Weekly repeated treatments using massage and TENS with BMWs for 5 weeks result ed in a decrease of NRS , but there were no significant differences between the TENS plus massage and sham TENS plus massage groups . Conclusions . This study shows that TENS with BMWs significantly inhibits chronic back pain , and treatment effects are attained within a day . The results also suggest that there were no statistically significant long-term effects of TENS with BMW in the repeated treatment UNLABELLED Transcutaneous electrical nerve stimulation ( TENS ) is an electrophysical modality used for pain management . This study investigated the dose response of different TENS intensities on experimentally induced pressure pain . One hundred and thirty TENS naïve healthy individuals ( 18 - 64 years old ; 65 males , 65 females ) were r and omly allocated to 5 groups ( n = 26 per group ) : Strong Non Painful TENS ; Sensory Threshold TENS ; Below Sensory Threshold TENS ; No Current Placebo TENS ; and Transient Placebo TENS . Active TENS ( 80 Hz ) was applied to the forearm for 30 minutes . Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds ( PPT ) were recorded from 2 points on the h and and forearm before and after TENS to measure hypoalgesia . There were significant differences between groups at both the h and and forearm ( ANOVA ; P = .005 and .002 ) . At 30 minutes , there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to : Below Sensory Threshold TENS , No Current Placebo TENS and Transient Placebo TENS groups ( P < .0001 ) at the forearm ; Transient Placebo TENS and No Current Placebo TENS groups at the h and ( P = .001 ) . There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups . The area under the curve for the changes in PPT significantly correlated with the current amplitude ( r(2 ) = .33 , P = .003 ) . These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes . PERSPECTIVE This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect ; thus , we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief CONTEXT AND OBJECTIVE Transcutaneous electrical nerve stimulation ( TENS ) and interferential current are the most used electrotherapy methods , although there is little scientific evidence to support their use . The aim of this study was to compare the effects of TENS and interferential current among patients with nonspecific chronic low back pain . DESIGN AND SETTING Single-blind r and omized controlled trial in the Department of Physiotherapy , Centro Universitário de Maringá . METHODS One hundred and fifty patients were r and omly divided into three groups : TENS ( group 1 ) , interferential current ( group 2 ) and controls ( group 3 ) . The patients design ated for electrotherapy received ten 30-minute sessions , while the control group remained untreated . All patients and controls were evaluated before and after treatment using a visual analog scale and the McGill Pain and Rol and Morris question naires , and regarding their use of additional medications . RESULTS There was a mean reduction on the visual analog scale of 39.18 mm with TENS , 44.86 mm with interferential current and 8.53 mm among the controls . In the Rol and Morris question naire , group 1 had a mean reduction of 6.59 ; group 2 , 7.20 ; and group 3 , 0.70 points . In group 1 , 84 % of the patients stopped using medications after the treatment ; in group 2 , 75 % ; and in group 3 , 34 % . There was no statistically significant difference between the TENS and interferential current groups ( P > 0.05 ) ; a difference was only found between these groups and the controls ( P < 0.0001 ) . CONCLUSION There was no difference between TENS and interferential current for chronic low back pain treatment . CLINICAL TRIAL REGISTRATION NCT01017913 Background In the currently available research publications on electrical therapy of low back pain , generally no control groups or detailed r and omization were used , and such studies were often conducted with relatively small groups of patients , based solely on subjective question naires and pain assessment scales ( lacking measurement methods to objectify the therapeutic progress ) . The available literature also lacks a comprehensive and large-scale clinical study . The purpose of this study was to assess the effects of treating low back pain using selected electrotherapy methods . The study assesses the influence of individual electrotherapeutic treatments on reduction of pain , improvement of the range of movement in lower section of the spine , and improvement of motor functions and mobility . Material / Methods The 127 patients qualified for the therapy ( ultimately , 123 patients completed the study ) and assigned to 6 comparison groups : A – conventional TENS , B – acupuncture-like TENS , C – high-voltage electrical stimulation , D – interferential current stimulation , E – diadynamic current , and F – control group . Results The research showed that using electrical stimulation with interferential current penetrating deeper into the tissues results in a significant and more efficient elimination of pain , and an improvement of functional ability of patients suffering from low back pain on the basis of an analysis of both subjective and objective parameters . The TENS currents and high voltage were helpful , but not as effective . The use of diadynamic currents appears to be useless . Conclusions Selected electrical therapies ( interferential current , TENS , and high voltage ) appear to be effective in treating chronic low back pain Background Chronic pain is a public health problem although there is a paucity of prevalence data from countries in the Middle East and North Africa . The aim of this study was to estimate the prevalence of chronic pain and neuropathic pain in a sample of the general adult population in Libya . Methods A cross-sectional telephone survey was conducted before the onset of the Libyan Civil War ( February 2011 ) on a sample of self-declared Libyans who had a l and line telephone and were at least 18 years of age . R and om sampling of household telephone number dialling was undertaken in three major cities and interviews conducted using an Arabic version of the Structured Telephone Interviews Question naire on Chronic Pain previously used to collect data in Europe . In addition , an Arabic version of S-LANSS was used . 1212 individuals were interviewed ( response rate = 95.1 % , mean age = 37.8 ± 13.9 years , female = 54.6 % ) . Results The prevalence of chronic pain ≥ 3 months was 19.6 % ( 95 % CI 14.6 % to 24.6 % ) with a mean ± SD duration of pain of 6 · 5 ± 5 · 7 years and a higher prevalence for women . The prevalence of neuropathic pain in the respondents reporting chronic pain was 19 · 7 % ( 95 % CI 14 · 6 - 24 · 7 ) , equivalent to 3 · 9 % ( 95 % CI 2 · 8 to 5 · 0 % ) of the general adult population . Only , 71 ( 29 · 8 % ) of respondents reported that their pain was being adequately controlled . Conclusions The prevalence of chronic pain in the general adult population of Libya was approximately 20 % and comparable with Europe and North America . This suggests that chronic pain is a public health problem in Libya . Risk factors are being a woman , advanced age and unemployment . There is a need for improved health policies in Libya to ensure that patients with chronic pain receive effective management OBJECTIVE To compare the effectiveness of transcutaneous electrical nerve stimulation and interferential current in primary dysmenorrhea . DESIGN A prospect i ve , r and omized , and controlled study . SETTING Hacettepe University School of Physical Therapy and Rehabilitation . PATIENTS Thirty-four volunteer subjects with primary dysmenorrhea ( mean age : 21.35 + /- 1.70 years ) were included . Statistical analyses were performed in 32 subjects who completed all measures . INTERVENTIONS Fifteen subjects received interferential current application for 20 minutes and 17 subjects received transcutaneous electrical nerve stimulation for 20 minutes when they were experiencing dysmenorrhea . OUTCOME MEASURES Physical characteristics , years since menarche , length of menstrual cycle ( days ) , and duration of menstruation ( days ) were recorded . Visual analog scale ( VAS ) intensities of menstrual pain , referred lower limb pain , and low back pain were recorded before treatment , and immediately , 8 hours , and 24 hours after treatment . RESULTS Intensities of the evaluated parameters decreased beginning from just after the applications in both groups ( P<0.05 ) . Intensity of referring low back pain in first three measurement times was different between the groups ( P<0.05 ) , but this difference is thought to be due to the baseline values of the groups . So , it can be said that no superiority existed between the methods ( P>0.05 ) . CONCLUSION Both transcutaneous electrical nerve stimulation and interferential current appear to be effective in primary dysmenorrhea . As they are free from the potentially adverse effects of analgesics , and no adverse effects are reported in the literature nor observed in this study , a clinical trial of their effectiveness in comparison with untreated and placebo-treated control groups is warranted Abstract We assessed the effectiveness of interferential current ( IFC ) and transcutaneous electrical nerve stimulation ( TENS ) therapies in the management of carpal tunnel syndrome ( CTS ) compared with splint therapy , a st and ard treatment modality for CTS . This was a prospect i ve , single-blinded , single-center , r and omized , three-group parallel intervention study of 3 weeks duration . Efficacy was examined in the third week after the end of treatments . Subjects were assigned r and omly to one of three groups : group I patients received splint therapy , group II patients received TENS applied on the palmar surface of the h and and the carpal tunnel , and group III patients underwent IFC therapy applied on the palmar surface of the h and and the volar surface of the forearm . TENS and ICF treatments were applied five times weekly for a total of 15 sessions . Group 1 patients were stabilized with volar wrist splints for 3 weeks . The efficacy of the therapies was assessed before initiation of therapy and at 3 weeks after completion of therapy using a visual analog scale ( VAS ) , a symptom severity scale , the functional capacity scale of the BCTQ , and measurement of median nerve motor distal latency ( mMDL ) and median sensory nerve conduction velocity ( mSNCV ) . Groups were compared pairwise using the Mann – Whitney U test to identify the source of differences between groups . The Wilcoxon test was used to analyze changes in variables over time within a group . In the VAS , BCTQ , MDL , and mSNCV , no significant difference was observed between the groups ( p > 0.05 ) . In the VAS , BCTQ , and mSNCV , statistically significant improvements were detected in all groups ( p < 0.05 ) . There was no statistically significant difference between TENS and splint therapy with respect to improvement in clinical scores , whereas IFC therapy provided a significantly greater improvement in VAS , mMDL , and mSNCV values than splint therapy ( VAS : 4.80 ± 1.18 and 6.37 ± 1.18 ; p = 0.001 , mMDL : 3.89 ± 0.88 and 4.06 ± 0.61 ; p = 0.001 , mSNCV : 41.80 ± 1.76 and 40.75 ± 1.48 ; p = 0.010 ) . IFC therapy provided a significantly greater improvement in VAS , symptom severity , functional capacity , and mMDL and mSNCV values than TENS therapy ( VAS : 4.80 ± 1.18 and 6.68 ± 1.42 ; p < 0.001 , symptom severity : 2.70 ± 1.03 and 3.37 ± 1.21 ; p = 0.015 , functional capacity : 1.90 ± 1.21 and 2.50 ± 0.78 ; p = 0.039 , mMDL : 3.89 ± 0.88 and 4.06 ± 0.88 ; p = 0.003 , and mSNCV : 41.80 ± 1.76 and 41.38 ± 1.78 ; p = 0.021 ) . IFC may be considered a new and safe therapeutic option for the treatment of CTS Some have proposed the use of transcutaneous electrical nerve stimulation ( TENS ) as an adjunct to the current st and ard of care in treatment of osteoarthritis knee pain . The purpose of this study was to evaluate the effects of TENS on the following issues in patients who have early-stage osteoarthritis of the knee : ( 1 ) pain reduction ; ( 2 ) subjective and ( 3 ) objective functional improvements ; ( 4 ) quality -of-life ( QOL ) measure improvements ; and ( 5 ) isokinetic strength . A prospect i ve , r and omized , and single-blinded trial was performed on 23 patients who were r and omized to either novel TENS device or st and ard of care . Metrics analyzed included stair-climb test ; timed-up- and -go test ( TUGT ) ; 2-minute walk test ; 20 times , single leg 6-inch step test ; five-repetition chair-rise test ; active and passive range-of-motion ( ROM ) score ; short form health survey-36 scores ( SF-36 ) score ; Knee Society Score ( KSS ) ; lower extremity functional scale ( LEFS ) ; visual analog scale ( VAS ) ; and isokinetic quadriceps and hamstring strength . In objective functional scores , TENS had significant improvements in TUGT and objective KSS when compared with the matching cohort . Subjective functional and QOL outcomes patients had a significant improvement of their LEFS and SF-36 physical component with the use of TENS brace . The TENS device significantly improved the quadriceps strength when compared with st and ard therapy . In evaluation for improvement within the TENS cohort , patients had a significant improvement at 3-month follow-up in the TUG test , timed stair-climb test , 20-times single leg , KSS , LEFS , and SF-36 physical component compared to their initial visit . In addition , within the TENS cohort , patients had a significant reduction in pain via VAS at their 3-month follow-up . In conclusion , the use of TENS for 3 months has shown encouraging results to improve pain , function , and QOL in patients with painful osteoarthritic knees , and could positively contribute as an adjunct to current nonoperative treatment of knee arthritis . However , given our small sample size , larger r and omized studies are needed to further evaluate these outcomes & NA ; Transcutaneous electrical nerve stimulation ( TENS ) is a noninvasive modality used to control pain . Animal models show that repeated TENS application produces analgesic tolerance and cross‐tolerance at spinal opioid receptors . The aim of the present investigation was to examine whether repeated application of TENS produces analgesic tolerance in humans . One hundred healthy subjects were r and omly assigned to 1 of 4 groups : control , placebo , low‐frequency ( 4 Hz ) or high‐frequency ( 100 Hz ) TENS . TENS was applied daily for 5 days to the nondominant upper limb ; pressure‐pain threshold ( PPT ) measurements were recorded before and after TENS . Temporal summation to mechanical stimulation was recorded on days 1 and 5 , before and after TENS . Diffuse noxious inhibitory control ( DNIC ) was tested on day 5 using the cold pressor test and PPT measurements . There was an initial increase in PPTs in both low‐ and high‐frequency TENS groups when compared with placebo or control groups . However , by day 5 this TENS‐induced increase in PPT did not occur , and there was no difference between active TENS and placebo or control groups . High‐frequency TENS decreased temporal summation on day 1 when compared with day 5 . DNIC increased the PPT similarly in all groups . These data suggest that repeated daily application of TENS results in a decrease in its hypoalgesic effect by the fifth day and that the tolerance‐like effect to repeated TENS results from tolerance at central ly located opioid receptors . The lack of change in DNIC response suggests that TENS and DNIC utilize separate pathways to produce analgesia . Repeated high‐frequency and low‐frequency transcutaneous electrical nerve stimulation produce analgesic tolerance in humans by the fourth and fifth day of treatment , respectively OBJECTIVE This study investigated the benefits of the combination of interferential ( IF ) and patterned muscle stimulation in the treatment of osteoarthritis ( OA ) of the knee . DESIGN This was a multi-center , r and omized , single-blind , controlled study with an independent observer . The study r and omized 116 patients with OA of the knee to a test or control group . The test group received 15 min of IF stimulation followed by 20 min of patterned muscle stimulation . The control group received 35 min of low-current transcutaneous electrical nerve stimulation ( TENS ) . Both groups were treated for 8 weeks . Subjects completed question naires at baseline and after 2 , 4 and 8 weeks . Primary outcomes included the pain and physical function subscales of the Western Ontario MacMaster ( WOMAC ) OA Index and Visual Analog Scales ( VAS ) for pain and quality of life . RESULTS Compared to the control group , the test group showed reduced pain and increased function . The test group showed a greater decrease in the WOMAC pain subscale ( P=0.002 ) , function subscale ( P=0.003 ) and stiffness subscale ( P=0.004 ) . More than 70 % of the test group , compared to less than 50 % of the control group , had at least a 20 % reduction in the WOMAC pain subscale . When analyzing only patients who completed the study , the test group had a nominally significant greater decrease in overall pain VAS . No significant between-group differences were observed in incidence of adverse events . CONCLUSIONS In patients with OA of the knee , home-based patterned stimulation appears to be a promising therapy for relieving pain , decreasing stiffness , and increasing function BACKGROUND AND OBJECTIVE The Physiotherapy Evidence Data base ( PEDro ) scale has been widely used to investigate method ological quality in physiotherapy r and omized controlled trials ; however , its validity has not been tested for pharmaceutical trials . The aim of this study was to investigate the validity and interrater reliability of the PEDro scale for pharmaceutical trials . The reliability was also examined for the Cochrane Back and Neck ( CBN ) Group risk of bias tool . METHODS This is a secondary analysis of data from a previous study . We considered r and omized placebo controlled trials evaluating any pain medication for chronic spinal pain or osteoarthritis . Convergent validity was evaluated by correlating the PEDro score with the summary score of the CBN risk of bias tool . The construct validity was tested using a linear regression analysis to determine the degree to which the total PEDro score is associated with treatment effect sizes , journal impact factor , and the summary score for the CBN risk of bias tool . The interrater reliability was estimated using the Prevalence and Bias Adjusted Kappa coefficient and 95 % confidence interval ( CI ) for the PEDro scale and CBN risk of bias tool . RESULTS Fifty-three trials were included , with 91 treatment effect sizes included in the analyses . The correlation between PEDro scale and CBN risk of bias tool was 0.83 ( 95 % CI 0.76 - 0.88 ) after adjusting for reliability , indicating strong convergence . The PEDro score was inversely associated with effect sizes , significantly associated with the summary score for the CBN risk of bias tool , and not associated with the journal impact factor . The interrater reliability for each item of the PEDro scale and CBN risk of bias tool was at least substantial for most items ( > 0.60 ) . The intraclass correlation coefficient for the PEDro score was 0.80 ( 95 % CI 0.68 - 0.88 ) , and for the CBN , risk of bias tool was 0.81 ( 95 % CI 0.69 - 0.88 ) . CONCLUSION There was evidence for the convergent and construct validity for the PEDro scale when used to evaluate method ological quality of pharmacological trials . Both risk of bias tools have acceptably high interrater reliability |
10,366 | 29,608,603 | Levels of blood glucose and HbA1c were associated with several HRV parameters , as well as Time from diagnosis of T2DM .
T2DM was associated with an overall decrease in the HRV of T2DM patients .
Both sympathetic and parasympathetic activity were decreased , which can be explained by the deleterious effects of altered glucose metabolism on HRV , leading to cardiac autonomic neuropathy | BACKGROUND Cardiac autonomic neuropathy in type 2 dibetes mellitus ( T2DM ) patients is frequent and associated with high cardiovascular mortality .
Heart rate variability ( HRV ) is the gold st and ard to measure cardiac autonomic neuropathy .
We aim ed to conduct a systematic review and meta- analysis to evaluate the impact of T2DM on HRV parameters . | Background Diabetes may confer an increased risk for the cardiovascular health effects of particulate air pollution , but few human clinical studies of air pollution have included people with diabetes . Ultrafine particles ( UFP , ≤100 nm in diameter ) have been hypothesized to be an important component of particulate air pollution with regard to cardiovascular health effects . Methods 17 never-smoker subjects 30–60 years of age , with stable type 2 diabetes but otherwise healthy , inhaled either filtered air ( 0–10 particles/cm3 ) or elemental carbon UFP ( ~107 particles/cm3 , ~50 ug/m3 , count median diameter 32 nm ) by mouthpiece , for 2 hours at rest , in a double-blind , r and omized , crossover study design . A digital 12-lead electrocardiogram ( ECG ) was recorded continuously for 48 hours , beginning 1 hour prior to exposure . Results Analysis of 5-minute segments of the ECG during quiet rest showed reduced high-frequency heart rate variability with UFP relative to air exposure ( p = 0.014 ) , paralleled by non-significant reductions in time-domain heart rate variability parameters . In the analysis of longer duration s of the ECG , we found that UFP exposure increased the heart rate relative to air exposure . During the 21- to 45-hour interval after exposure , the average heart rate increased approximately 8 beats per minute with UFP , compared to 5 beats per minute with air ( p = 0.045 ) . There were no UFP effects on cardiac rhythm or repolarization . Conclusions Inhalation of elemental carbon ultrafine particles alters heart rate and heart rate variability in people with type 2 diabetes . Our findings suggest that effects may occur and persist hours after a single 2-hour exposure Previous reports suggest that inflammatory bowel diseases may be accompanied by abnormalities in the neural autonomic profile . We tested the hypotheses that 1 ) an exaggerated sympathetic activity characterizes active ulcerative colitis ( UC ) and 2 ) a reduction of sympathetic activity by clonidine would be associated with clinical changes of UC . In 23 patients with UC and 20 controls , muscle sympathetic nerve activity ( MSNA ) , ECG , blood pressure , and respiration were continuously recorded , and plasma catecholamine was evaluated both at rest and during a 75 degrees head-up tilt . Autonomic profile was assessed by MSNA , norepinephrine , epinephrine , spectral markers of low-frequency ( LF ) cardiac sympathetic ( LF(RR ) ; normalized units ) and high-frequency ( HF ) parasympathetic ( HF(RR ) ; normalized units ) modulation and sympathetic vasomotor control ( LF systolic arterial pressure ; LF(SAP ) ) , obtained by spectrum analysis of the R-R interval and systolic pressure variability . Among UC patients , 16 agreed to be r and omly assigned to 8-wk transdermal clonidine ( 15 mg/wk , 9 subjects ) , or placebo ( 7 patients ) . An autonomic profile , Disease Activity Index ( DAI ) , and endoscopic pattern were compared before and after clonidine/placebo . At rest , MSNA , heart rate ( HR ) , LF(RR ) , LF/HF , and LF(SAP ) were higher and HF(RR ) was lower in patients than in controls . Tilt decreased HF(RR ) and increased MSNA and LF(RR ) less in patients than in controls . Clonidine decreased HR , MSNA , epinephrine , LF(RR ) , and increased HF(RR ) , whereas placebo had no effects . Changes of the autonomic profile after clonidine were associated with reduction of DAI score . An overall increase of sympathetic activity characterized active UC . Normalization of the autonomic profile by clonidine was accompanied by an improvement of the disease Epidemic of diabetes , affecting about 3–5 % of Western population s , is one of the main threats to human health in the 21st century ( 1 ) . Changes in the human environment , behavior , and lifestyle have result ed in a dramatic increase in the incidence and prevalence of diabetes in people with genetic susceptibility to diabetes . The global number of people with diabetes was 151 million in 2000 , and it is projected to increase to 221 million in 2010 ( an increase of 46 % ) both in developed and developing countries ( 2 ) . Chronic hyperglycemia leads to many long-term complications in the eyes , kidneys , nerves , heart , and blood vessels . Individuals with pre-diabetes , undiagnosed type 2 diabetes , and long-lasting type 2 diabetes are at high risk of all complications of macrovascular disease , coronary heart disease ( CHD ) , stroke , and peripheral vascular disease . More than 70 % of patients with type 2 diabetes die of cardiovascular causes ( 3 ) . Therefore , the epidemic of type 2 diabetes will be followed by an epidemic of diabetes-related cardiovascular disease ( CVD ) . Over the years , epidemiological studies have produced important information on the prevalence and incidence of diabetes complications in different population s. They have also given important information on different risk factors determining susceptibility to diabetes complications ( Fig. 1 ) . This information is crucial for mechanistic studies in physiology at the tissue level and for molecular biology studies at the cellular level . A good example is glycated hemoglobin . Several studies have indicated that glycated hemoglobin is associated with diabetes complications in prospect i ve epidemiological studies . That information has been crucial for the planning of clinical trials to test the hypothesis that the treatment of chronic hyperglycemia leads to reduction in long-term diabetes complications . Moreover , information from epidemiology has led to several mechanistic studies and the elucidation of molecular level insights how insulin resistance and hyperglycemia lead to diabetes complications . We examined whether an injection of intravenous insulin and intravenous glucose would affect frequency-domain measures of heart rate variability ( HRV ) , i.e. , the high-frequency ( HF- ) b and and the ratio of the low frequency ( LF- ) to the HF-b and in healthy humans . Using a classical conditioning protocol , we also assessed whether the measures of HRV are subject to classical conditioning . Thirty healthy men were divided into three groups , given a conditioned stimulus ( CS ) and an intravenous injection of either insulin ( 0.05IU/kg ) in Group 1 , glucose ( 15 % , 0.5g/kg ) in Group 2 , or placebo ( physiological saline [ 0.9 % ] ) in Group 3 during the 4-day acquisition phase . All subjects were given an olfactory CS ( rosewood-peppermint smell ) and placebo injection on day 5 ( test ) . Due to their high inter-individual variability , HF and LF/HF-ratio were analysed by intragroup comparisons , using a pre-injection baseline interval ( min -15 to -5 ) , and three functional post-injection intervals : a ) the interval to the maximum insulin level , i. e. insulin peak ( min 0 - 5 ) in Groups 1 and 2 , b ) the interval to the maximum of insulin-induced hypoglycaemia ( min 20 - 25 ) in Group 1 , and c ) the end of the session ( min 70 - 75 ) . On days 1 to 4 , we found significant increases of the HF-b and from baseline to interval min 0 - 5 in Group 1 , and an even more pronounced increase in the glucose-treated Group 2 . At the test ( Day 5 ) , both experimental groups responded with an HF-increase in the interval of the former insulin peak , and also at the other measurement intervals , reflecting some general increase of vagal activity remaining as a conditioned response . On days 1 to 4 , the HF-b and was positively correlated with the change of peripheral insulin levels in Group 1 , reaching statistical significance on days 3 and 4 . This pattern only emerged in tendency on Day 4 in Group 2 . In conclusion , insulin triggers an increase in parasympathetic tone at maximum hyperinsulinaemia , and our data support the notion that this response pattern can become classically conditioned Introduction The need for colonoscopy is common among diabetics . In this study , we aim ed to evaluate the effect of autonomous neuropathy on bowel preparation in type 2 diabetes mellitus ( DM ) patients . Material s and methods The study population consisted of 45 patients with DM and 48 non-diabetic , age- and sex-matched subjects . All colonoscopies were performed 5 h after the last dose of sodium phosphate . Colonoscopists rated the bowel preparation quality during the procedure using the Aronchick scale . All patients underwent a detailed cardiologic examination and 24-h Holter rhythm monitoring . Orthostatic hypotension and impairment in heart rate variability were accepted as indicators of autonomous neuropathy . Results Gender , age , blood pressure , and heart rates did not differ significantly between groups ( p > 0.05 ) . Autonomous neuropathy was detected in 14 ( 31.1 % ) patients in the DM group and in two ( 4.2 % ) in the control group ( p < 0.05 ) . Optimal bowel cleansing was achieved in 93.8 % of controls and 73.3 % of diabetics ; bowel cleansing was suboptimal in 26.7 % of diabetics and 6.2 % of controls ( p < 0.05 ) . Optimal bowel cleansing was achieved in six of 14 ( 42.8 % ) diabetic patients with autonomous neuropathy ; however , optimal bowel cleansing was achieved in 27 of 31 ( 87.1 % ) diabetic patients without autonomous neuropathy ( p < 0.05 ) . Although optimal bowel cleansing was more prevalent among control patients than in diabetic patients without autonomous neuropathy , the difference was not significant ( 87.1 % vs 93.8 % ; p > 0.05 ) . Conclusion These data suggest that optimal bowel cleansing is poorer in diabetics with autonomous neuropathy than in those without autonomous neuropathy and controls Objectives Appropriate reporting is central to the application of findings from research to clinical practice . The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) recommendations consist of a checklist of 22 items that provide guidance on the reporting of cohort , case – control and cross-sectional studies , in order to facilitate critical appraisal and interpretation of results . STROBE was published in October 2007 in several journals including The Lancet , BMJ , Annals of Internal Medicine and PLoS Medicine . Within the framework of the revision of the STROBE recommendations , the authors examined the context and circumstances in which the STROBE statement was used in the past . Design The authors search ed the Web of Science data base in August 2010 for articles which cited STROBE and examined a r and om sample of 100 articles using a st and ardised , piloted data extraction form . The use of STROBE in observational studies and systematic review s ( including meta-analyses ) was classified as appropriate or inappropriate . The use of STROBE to guide the reporting of observational studies was considered appropriate . Inappropriate uses included the use of STROBE as a tool to assess the method ological quality of studies or as a guideline on how to design and conduct studies . Results The authors identified 640 articles that cited STROBE . In the r and om sample of 100 articles , about half were observational studies ( 32 % ) or systematic review s ( 19 % ) . Comments , editorials and letters accounted for 15 % , method ological articles for 8 % , and recommendations and narrative review s for 26 % of articles . Of the 32 observational studies , 26 ( 81 % ) made appropriate use of STROBE , and three uses ( 10 % ) were considered inappropriate . Among 19 systematic review s , 10 ( 53 % ) used STROBE inappropriately as a tool to assess study quality . Conclusions The STROBE reporting recommendations are frequently used inappropriately in systematic review s and meta-analyses as an instrument to assess the method ological quality of observational studies To investigate the effects of obesity and weight loss on cardiovascular autonomic function , we examined 28 obese patients referred for weight-reducing gastroplasty , 24 obese patients who received dietary recommendations , and 28 lean subjects . Body weight , blood pressure , and 24-hour urinary norepinephrine excretion were measured , and time and frequency domain indexes of heart rate variability ( HRV ) were obtained from 24-hour Holter recordings . A measure of long-term HRV , the SD of all normal RR intervals ( SDANN ) , was used as an index of sympathetic activity and the high-frequency ( HF ) component of the frequency domain , reflecting short-term HRV , as an estimate of vagal activity . All 3 study groups were investigated at baseline , and the 2 obese groups were reexamined at 1-year follow-up . Obese patients had higher blood pressure , higher urinary norepinephrine excretion , and attenuated SDANN and HF values than lean subjects ( p < 0.01 ) . Obese patients treated with surgery had a mean weight loss of 32 kg ( 28 % ) , whereas the obese group treated with dietary recommendations remained weight stable ( p < 0.001 ) . At follow-up the weight-loss group displayed decreases in blood pressure and norepinephrine excretion and showed increments in SDANN and HF values . These changes were significantly greater than those observed in the obese control group ( p < 0.05 ) . Our findings suggest that obese patients have increased sympathetic activity and a withdrawal of vagal activity and that these autonomic disturbances improve after weight loss This study sought to determine if the severity of autonomic perturbations in patients with heart failure are affected by the presence of diabetes . Decreased HRV is frequent in diabetic patients free of clinical ly apparent heart disease and has been invoked as a risk factor for sudden cardiac death . However , reduced HRV is also commonly present in patients with left ventricular dysfunction . The effect of diabetes on autonomic dysfunction in this setting is not known . Holter ECGs from 69 diabetic patients and 85 nondiabetic control subjects with heart failure were analyzed . The severity of autonomic dysfunction was assessed using 24-hour time- and frequency-domain HRV analysis . Prognostically important time- and frequency-domain HRV measures ( SDNN , SDANN5 , total power , and ultra-low frequency power ) were not different between the two groups . Time- and frequency-domain parameters modulated by parasympathetic tone ( pNN50 , RMSSD , and HF power ) were depressed to a similar degree in the diabetic and the nondiabetic groups . The low frequency power was significantly lower in diabetic patients ( 5.8 + /- 0.7 vs 5.3 + /- 1.0 , P = 0.02 ) . The ratio of low to high frequency power was substantially lower in the diabetic group ( 2.2 + /- 0.2 vs 1.4 + /- 0.2 , P < 0.0001 ) . These differences were more apparent in insulin-treated diabetics . In the presence of heart failure , HRV parameters that are most predictive of adverse outcome are similar in diabetic and nondiabetic patients . Furthermore , during increased sympathetic stimulation in the setting of heart failure , diabetes does not worsen parasympathetic withdrawal but may mitigate sympathetic activation 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 |
10,367 | 26,316,054 | ConclusionS afety data on CZP suggest an overall favorable tolerability profile , with infections being the most common AE .
However , CZP-treated patients had a twofold higher risk of infectious SAEs than control patients .
Large observational studies and data from national registries are needed to detect rare AEs , which might occur after long-term exposures to CZP | Introduction Certolizumab pegol ( CZP ) , an anti-tumor necrosis factor PEGylated Fab ’ fragment of a humanized monoclonal antibody , is currently approved for treatment of some immune-mediated inflammatory diseases ( IMIDs ) .
To our knowledge , no systematic review and meta- analysis evaluating the overall safety profile of CZP has been performed .
Objective The objective of this systematic review was to assess the adverse event ( AE ) patterns of CZP versus a control in patients with IMIDs . | Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-PsA ( NCT01087788 ) , an ongoing Phase 3 trial in patients with psoriatic arthritis ( PsA ) . Methods Patients were r and omised 1:1:1 to placebo , 200 mg CZP every 2 weeks ( Q2W ) or 400 mg CZP every 4 weeks ( Q4W ) . Patients could have had exposure to one previous tumour necrosis factor ( TNF ) inhibitor therapy . Primary endpoints were American College of Rheumatology 20 % ( ACR20 ) response at week 12 and modified Total Sharp Score change from baseline at week 24 . Secondary endpoints included ; Psoriatic Arthritis Response Criteria ( PsARC ) score , Health Assessment Question naire Disability Index ( HAQ-DI ) , Psoriasis Area and Severity Index , Leeds Enthesitis Index , Leeds Dactylitis Index , and Modified Nail Psoriasis Severity Index . Results Of 409 patients r and omised , 368 completed 24 weeks of treatment . ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo ( 58.0 % and 51.9 % vs 24.3 % ( p<0.001 ) ) at week 12 , with improvements observed by week 1 . There was a statistically significant improvement in physical function from baseline , measured by HAQ-DI in CZP patients compared with placebo ( −0.50 vs −0.19 , p<0.001 ) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo ( 78.3 % and 77.0 % vs 33.1 % ( p<0.001 ) ) . Sustained improvements were observed in psoriatic skin involvement , enthesitis , dactylitis and nail disease . Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure . No new safety signals were observed . Conclusions Rapid improvements in the signs and symptoms of PsA , including joints , skin , enthesitis , dactylitis and nail disease were observed across both CZP dosing regimens Background : Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor . Objective : To evaluate the efficacy and safety of certolizumab pegol versus placebo , plus methotrexate ( MTX ) , in patients with active rheumatoid arthritis ( RA ) . Methods : An international , multicentre , phase 3 , r and omised , double-blind , placebo-controlled study in active adult-onset RA . Patients ( n = 619 ) were r and omised 2:2:1 to subcutaneous certolizumab pegol ( liquid formulation ) 400 mg at weeks 0 , 2 and 4 followed by 200 mg or 400 mg plus MTX , or placebo plus MTX , every 2 weeks for 24 weeks . The primary end point was ACR20 response at week 24 . Secondary end points included ACR50 and ACR70 responses , change from baseline in modified Total Sharp Score , ACR core set variables and physical function . Results : Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo ( p⩽0.001 ) ; rates were 57.3 % , 57.6 % and 8.7 % , respectively . Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression ; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4 , respectively , versus 1.2 for placebo ( rank analysis p⩽0.01 ) . Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo ; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50 , respectively , versus −0.14 for placebo ( p⩽0.001 ) . Most adverse events were mild or moderate , with low incidence of withdrawals due to adverse events . Five patients developed tuberculosis . Conclusion : Certolizumab pegol plus MTX was more efficacious than placebo plus MTX , rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression . Trial registration number : Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose 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 This 52-week , r and omised , double-blind phase IIIb study assessed efficacy and safety of certolizumab pegol ( CZP ) as add-on therapy to non-biologic disease-modifying antirheumatic drugs ( DMARDs ) in rheumatoid arthritis ( RA ) patients with low to moderate disease activity , and stopping therapy in patients in sustained remission . Methods Patients were r and omised 1:1 to CZP ( 400 mg at weeks 0 , 2 and 4 , then 200 mg every 2 weeks ) or placebo ( every 2 weeks ) plus current non-biologic DMARDs . At week 24 , patients who achieved the primary endpoint of Clinical Disease Activity Index ( CDAI ) remission at both weeks 20 and 24 stopped study treatment and continued in the study until week 52 . Results Of 194 patients ( CZP=96 ; placebo=98 ) , > 90 % had moderate disease activity at baseline . Significantly more CZP patients met the primary endpoint than placebo patients ( week 20 and 24 CDAI remission rates : 18.8 % vs 6.1 % ; p≤0.05 ) . At week 24 , 63.0 % vs 29.7 % of CZP versus placebo patients ( p<0.001 ) achieved LDA . Disease activity score ( ESR ) based on 28-joint count and Simplified Disease Activity Index remission rates were also significantly higher with CZP versus placebo ( 19.8 % vs 3.1 % ; p≤0.01 and 14.6 % vs 4.1 % ; p≤0.05 ) . CZP patients reported improvements in physical function versus placebo ( mean Health Assessment Question naire-Disability-Index change from baseline : CZP , −0.25 vs placebo , −0.03 ; p≤0.01 ) . During the period following withdrawal of CZP or placebo , only 3/17 prior CZP patients and 2/6 prior placebo patients maintained CDAI remission until week 52 , but CZP reinstitution allowed renewed improvement . Adverse and serious adverse event rates were comparable between CZP and placebo groups . Conclusions Addition of CZP to non-biologic DMARDs is an effective treatment in RA patients with predominantly moderate disease activity , allowing low-disease activity or remission to be reached in a majority of the patients . However , the data suggest that CZP can not be withdrawn in patients achieving remission . Trial registration number NCT00674362 Abstract Objective . This 24-week , placebo-controlled , double-blind , r and omized study ( NCT00791921 ) investigated efficacy and safety of certolizumab pegol ( CZP ) in Japanese rheumatoid arthritis ( RA ) patients in whom methotrexate ( MTX ) can not be administered . Methods . A total of 230 patients were r and omized to subcutaneous CZP 200 mg ( induction dosing : 400 mg at Weeks 0 , 2 and 4 ) or placebo every 2 weeks . Results . ACR20 responses with CZP were rapid and significant versus placebo at Week 1 , sustained to Week 12 ( 67.2 % vs. 14.9 % ) and Week 24 ( 63.8 % vs. 11.4 % ) . Week 24-modified Total Sharp Score ( mTSS ) change from baseline ( CFB ) was 0.48 ( CZP ) versus 2.45 ( placebo ) . CZP treatment was associated with higher Week 12 ACR20 responses versus placebo ( with non-MTX disease modifying antirheumatic drugs [ DMARDs ] , 74.2 % vs. 20.0 % ; without [ monotherapy ] , 59.3 % vs. 8.2 % ) and inhibition of radiographic progression at Week 24 ( mTSS CFB ; with non-MTX DMARDs , 0.24 vs. 1.61 ; monotherapy , 0.68 vs. 3.65 ) . Incidences of serious adverse events were 11.2 % ( CZP ) and 2.6 % ( placebo ) ; one CZP patient died of dissecting aortic aneurysm . Conclusion . CZP treatment with and without non-MTX DMARDs in Japanese patients in whom MTX can not be administered result ed in rapid , sustained reductions in RA signs and symptoms . Notably , CZP monotherapy showed significant inhibition of radiographic progression Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-axSpA ( NCT01087762 ) , an ongoing Phase 3 trial in patients with axial spondyloarthritis ( axSpA ) , including patients with ankylosing spondylitis ( AS ) and non-radiographic axSpA ( nr-axSpA ) . Methods Patients with active axSpA were r and omised 1:1:1 to placebo , CZP 200 mg every 2 weeks ( Q2W ) or CZP 400 mg every 4 weeks ( Q4W ) . In total 325 patients were r and omised . Primary endpoint was ASAS20 ( Assessment of SpondyloArthritis international Society 20 ) response at week 12 . Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index ( BASFI ) , Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , and Bath Ankylosing Spondylitis Metrology Index ( BASMI ) linear . Results Baseline disease activity was similar between AS and nr-axSpA. At week 12 , ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo ( 57.7 and 63.6 vs 38.3 , p≤0.004 ) . At week 24 , combined CZP arms showed significant ( p<0.001 ) differences in change from baseline versus placebo in BASFI ( −2.28 vs −0.40 ) , BASDAI ( −3.05 vs −1.05 ) , and BASMI ( −0.52 vs −0.07 ) . Improvements were observed as early as week 1 . Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA sub population s. Adverse events were reported in 70.4 % vs 62.6 % , and serious adverse events in 4.7 % vs 4.7 % of All CZP versus placebo groups . No deaths or malignancies were reported . Conclusions CZP rapidly reduced the signs and symptoms of axSpA , with no new safety signals observed compared to the safety profile of CZP in RA . Similar improvements were observed across CZP dosing regimens , and in AS and nr-axSpA patients To investigate clinical efficacy and safety of 2 certolizumab pegol ( CZP ) maintenance dosing regimens plus methotrexate ( MTX ) in active rheumatoid arthritis ( RA ) patients achieving the American College of Rheumatology 20 % improvement criteria ( ACR20 ) after the CZP 200 mg every 2 weeks open‐label run‐in period OBJECTIVE To investigate the efficacy and safety of certolizumab pegol ( CZP ) in a broad population of patients with active RA . METHODS In this 12-week , double-blind period of the phase IIIb trial , RA patients with inadequate response to at least one DMARD were r and omized 4:1 to CZP ( 400 mg at weeks 0 , 2 and 4 , followed by 200 mg every 2 weeks ) or placebo ( every 2 weeks ) plus current therapy stratified by previous TNF inhibitor use , concomitant methotrexate use and disease duration ( < 2 vs ≥2 years ) . The primary outcome was ACR20 response rate at week 12 . RESULTS Of 1063 patients ( CZP = 851 ; placebo = 212 ) , 37.6 % had previous TNF inhibitor use . Baseline mean HAQ Disability Index ( HAQ-DI ) and DAS 28-joint assessment -ESR [ DAS28(ESR ) ] values were 1.5 and 6.4 in the CZP group , and 1.6 and 6.4 in the placebo group , respectively . The primary endpoint was significant ( week 12 ACR20 , CZP vs placebo : 51.1 vs 25.9 % ; P < 0.001 ) ; differences were noted at week 2 ( 31.8 vs 8.5 % ; P < 0.001 ) . HAQ-DI and DAS28(ESR ) change from baseline and ACR50 were significant from week 2 . Week 12 ACR20 responses were similar across CZP patient subgroups regardless of concomitant DMARD use at baseline . Adverse and serious adverse events were comparable between CZP and placebo , with no new safety signals . CONCLUSION CZP was associated with rapid and consistent clinical responses and improved physical function in a diverse group of RA patients , irrespective of concomitant or previous therapy . TRIAL REGISTRATION Clinical Trials.gov , http:// clinical trials.gov/ , NCT00717236 OBJECTIVE To evaluate the efficacy and safety of 2 dosage regimens of lyophilized certolizumab pegol ( a novel PEGylated anti-tumor necrosis factor agent ) as adjunctive therapy to methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) with an inadequate response to MTX therapy alone . METHODS In this 52-week , phase III , multicenter , r and omized , double-blind , placebo-controlled , parallel-group trial , 982 patients were r and omized 2:2:1 to receive treatment with subcutaneous certolizumab pegol at an initial dosage of 400 mg given at weeks 0 , 2 , and 4 , with a subsequent dosage of 200 mg or 400 mg given every 2 weeks , plus MTX , or placebo plus MTX . Co- primary end points were the response rate at week 24 according to the American College of Rheumatology 20 % criteria for improvement ( ACR20 ) and the mean change from baseline in the modified total Sharp score at week 52 . RESULTS At week 24 , ACR20 response rates using nonresponder imputation for the certolizumab pegol 200-mg and 400-mg groups were 58.8 % and 60.8 % , respectively , as compared with 13.6 % for the placebo group . Differences in ACR20 response rates versus placebo were significant at week 1 and were sustained to week 52 ( P < 0.001 ) . At week 52 , mean radiographic progression from baseline was reduced in patients treated with certolizumab pegol 200 mg ( 0.4 Sharp units ) or 400 mg ( 0.2 Sharp units ) as compared with that in placebo-treated patients ( 2.8 Sharp units ) ( P < 0.001 by rank analysis ) . Improvements in all ACR core set of disease activity measures , including physical function , were observed by week 1 with both certolizumab pegol dosage regimens . Most adverse events were mild or moderate . CONCLUSION Treatment with certolizumab pegol 200 or 400 mg plus MTX result ed in a rapid and sustained reduction in RA signs and symptoms , inhibited the progression of structural joint damage , and improved physical function as compared with placebo plus MTX treatment in RA patients with an incomplete response to MTX BACKGROUND & AIMS Certolizumab pegol ( CZP ) is a pegylated-conjugated Fab ' against tumor necrosis factor ( TNF ) . Additional data are needed regarding the efficacy of induction therapy with CZP in active Crohn 's disease ( CD ) . METHODS A placebo-controlled trial evaluated the efficacy of CZP therapy in 439 adults with moderate to severe CD naive to anti-TNF therapy . Patients were r and omized to receive CZP ( 400 mg subcutaneously ) or placebo at weeks 0 , 2 , and 4 . The primary end point was clinical remission at week 6 . RESULTS Clinical remission rates at week 6 in the CZP and placebo groups were 32 % and 25 % ( P = .174 ) , respectively . Remission rates at weeks 2 and 4 in the CZP and placebo groups were 23 % and 16 % ( P = .033 ) and 27 % and 19 % ( P = .063 ) , respectively . Clinical response rates at weeks 2 , 4 , and 6 in the CZP and placebo groups were 33 % and 20 % ( P = .001 ) , 35 % and 26 % ( P = .024 ) , and 41 % and 34 % ( P = .179 ) , respectively . There were significantly greater rates of clinical remission at week 6 for CZP in patients with increased concentrations of C-reactive protein ( ≥5 mg/L ) at entry . Serious adverse events developed in 5 % and 4 % of patients in the CZP and placebo groups , respectively . CONCLUSIONS The primary end point did not reach statistical significance . Significant differences between CZP and placebo were observed in patients who had increased concentrations of C-reactive protein when the study began . Future clinical trials should emphasize the treatment of patients who have objective evidence of inflammation in addition to symptoms of active disease Abstract Objectives . This 24-week , multicenter , double-blind , r and omized , placebo-controlled study ( NCT00791999 ) compared efficacy and safety of certolizumab pegol ( CZP ) in combination with methotrexate ( MTX ) vs placebo plus MTX in Japanese rheumatoid arthritis ( RA ) patients with inadequate response to MTX . Methods . In total , 316 patients were r and omized 1:1:1:1 to subcutaneous CZP 100 , 200 , or 400 mg ( induction dose : 200 mg or 400 mg CZP at Weeks 0 , 2 , and 4 ) plus MTX or placebo plus MTX every 2 weeks . Primary endpoint was ACR20 response at Week 12 . Results . ACR20 response rates were 62.5 % , 76.8 % , 77.6 % , and 28.6 % at Week 12 , and 61.1 % , 73.2 % , 71.8 % , and 24.7 % at Week 24 for CZP 100 , 200 , and 400 mg , and placebo groups , respectively , with statistical significance between each CZP group and placebo . Change in Total Sharp Score over 24 weeks was significantly smaller in CZP 200 and 400 mg groups vs placebo . Improvements in health-related quality of life ( HRQoL ) were observed in all three CZP groups vs placebo . Incidence of adverse events was similar between CZP groups . Conclusions . CZP plus MTX result ed in rapid , sustained reductions in RA signs and symptoms in Japanese patients with inadequate response to MTX , with significant inhibition of radiographic progression and improved OBJECTIVE Certolizumab pegol ( CZP ) is known to be effective as monotherapy at a dosage of 400 mg every 4 weeks in patients with active RA who have failed DMARDs . The aim of this study was to investigate every 4-week CZP in addition to continued MTX therapy in patients with an inadequate response to MTX alone . METHODS Patients with active RA with inadequate response to MTX , on background MTX , were r and omized to double-blind treatment with CZP 400 mg or placebo every 4 weeks for 24 weeks ( NCT00544154 ) . The primary efficacy end-point was the ACR 20 % improvement criteria ( ACR20 ) response rate at Week 24 . Other end-points included ACR50 and ACR70 response rates , ACR core components , 28-joint DAS ( ESR ) with three variables ( DAS28 - 3 ) and health-related quality -of-life outcomes in addition to safety . RESULTS Of 247 r and omized patients , 126 received CZP and 121 received placebo , in addition to MTX . ACR20 response rates were 45.9 vs 22.9 % , respectively [ P < 0.001 analysed by the Cochran-Mantel-Haenszel ( CMH ) method ] , with improvements being apparent from Week 1 . Statistically significant improvements over placebo were seen with CZP for ACR50 , ACR core components , DAS28 - 3 and physical functioning . Rates of treatment-related adverse events were similar between groups ( 25.0 vs 27.7 % ) , and there were no deaths or serious opportunistic infections . CONCLUSION CZP 400 mg every 4 weeks plus MTX demonstrated a favourable risk-benefit profile with rapid onset of action in RA patients with an inadequate response to an earlier MTX therapy Background Certolizumab pegol ( CZP ) is a PEGylated antitumour necrosis factor agent OBJECTIVE Biological products that neutralize tumour necrosis factor alpha ( TNF-alpha ) are beneficial in rheumatoid arthritis ( RA ) . We studied the effects of CDP870 , a novel anti-TNF-alpha antibody fragment modified to obtain a prolonged plasma half-life ( approximately 14 days ) . METHODS Thirty-six patients were r and omized in a double-blind , ascending-dose group study to a single intravenous infusion of placebo ( n = 12 ) or 1 , 5 or 20 mg/kg CDP870 ( each n = 8) . The patients were predominantly female ( 30/36 ) , had a mean age of 56 yr and a mean duration of RA of 13 years . They had received a mean of five DMARDs or experimental therapies ( with 1 month washout before the study started ) and had active disease . Continuation of NSAIDs and up to 7.5 mg prednisolone daily was allowed . Following the blinded dosing period , 32 patients received a single open-label infusion of either 5 or 20 mg/kg CDP870 . RESULTS In the blinded dosing period , 6/12 placebo patients withdrew from the study ( for deteriorating RA < or = 4 weeks after dosing ) . Two of 24 CDP870-treated patients withdrew , both in the 1 mg/kg group ( for deteriorating RA or lost to follow up > 4 weeks after dosing ) . The proportion of patients with ACR20 improvement for the per- protocol population with the last observation carried forward was 16.7 , 50 , 87.5 and 62.5 % after 0 , 1 , 5 and 20 mg/kg CDP870 respectively ( combined treatment effect , P = 0.012 , primary analysis ) at 4 weeks and 16.7 , 25 , 75 and 75 % ( P = 0.032 ) at 8 weeks . The proportion of patients with ACR50 improvement for the per- protocol population with the last observation carried forward was 0 , 12.5 , 12.5 and 50 % after 0 , 1 , 5 and 20 mg/kg CDP870 respectively ( combined treatment effect , P = 0.079 ) at 4 weeks and 0 , 12.5 , 12.5 and 50 % ( P = 0.079 ) at 8 weeks . Following the open-label dose of CDP870 , similar beneficial effects were achieved . CONCLUSION CDP870 is effective , was very well tolerated in this small study , and has an extended duration of action following one or more intravenous doses BACKGROUND Certolizumab pegol is a pegylated humanized Fab ' fragment with a high binding affinity for tumor necrosis factor alpha that does not induce apoptosis of T cells or monocytes . METHODS In our r and omized , double-blind , placebo-controlled trial , we evaluated the efficacy of certolizumab pegol maintenance therapy in adults with moderate-to-severe Crohn 's disease . As induction therapy , 400 mg of certolizumab pegol was administered subcutaneously at weeks 0 , 2 , and 4 . Patients with a clinical response ( defined as reduction of at least 100 from the baseline score on the Crohn 's Disease Activity Index [ CDAI ] ) at week 6 were stratified according to their baseline C-reactive protein level and were r and omly assigned to receive 400 mg of certolizumab pegol or placebo every 4 weeks through week 24 , with follow-up through week 26 . RESULTS Among patients with a response to induction therapy at week 6 ( 428 of 668 [ 64 % ] ) , the response was maintained through week 26 in 62 % of patients with a baseline C-reactive protein level of at least 10 mg per liter ( the primary end point ) who were receiving certolizumab pegol ( vs. 34 % of those receiving placebo , P<0.001 ) and in 63 % of patients in the intention-to-treat population who were receiving certolizumab pegol ( vs. 36 % receiving placebo , P<0.001 ) . Among patients with a response to induction therapy at week 6 , remission ( defined by a CDAI score of < or = 150 ) at week 26 was achieved in 48 % of patients in the certolizumab group and 29 % of those in the placebo group ( P<0.001 ) . The efficacy of certolizumab pegol was also shown in patients taking and those not taking glucocorticoids or immunosuppressants and in patients who had and those who had not previously taken infliximab . Infectious serious adverse events ( including one case of pulmonary tuberculosis ) occurred in 3 % of patients receiving certolizumab pegol and in less than 1 % of patients receiving placebo . Antinuclear antibodies developed in 8 % of the patients in the certolizumab group ; antibodies against certolizumab pegol developed in 9 % of all patients who entered the induction phase . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease who had a response to induction therapy with 400 mg of certolizumab pegol were more likely to have a maintained response and a remission at 26 weeks with continued certolizumab pegol treatment than with a switch to placebo . ( Clinical Trials.gov number , NCT00152425 [ Clinical Trials.gov ] . ) BACKGROUND & AIMS To investigate the efficacy and safety of certolizumab pegol ( a polyethylene-glycolated Fab ' fragment of anti-tumor necrosis factor , CDP870 ) in Crohn 's disease . METHODS In a placebo-controlled , phase II study , 292 patients with moderate to severe Crohn 's disease received subcutaneous certolizumab 100 , 200 , or 400 mg or placebo at weeks 0 , 4 , and 8 . The primary end point was the percentage of patients with a clinical response at week 12 ( a Crohn 's Disease Activity Index decrease of > or = 100 points or remission [ Crohn 's Disease Activity Index < or = 150 points ] ) in the intent-to-treat population . RESULTS All certolizumab doses produced significant clinical benefit over placebo at week 2 ( placebo , 15.1 % ; certolizumab 100 mg , 29.7 % [ P = .033 ] ; 200 mg , 30.6 % [ P = .026 ] ; 400 mg , 33.3 % [ P = .010 ] ) . At all time points , the clinical response rates were highest for certolizumab 400 mg , greatest at week 10 ( certolizumab 400 mg , 52.8 % ; placebo , 30.1 % ; P = .006 ) but not significant at week 12 ( certolizumab 400 mg , 44.4 % ; placebo , 35.6 % ; P = .278 ) . Patients with baseline C-reactive protein levels of 10 mg/L or greater ( n = 119 ) showed clearer separation between active treatment and placebo ( week 12 clinical response : certolizumab 400 mg , 53.1 % ; placebo , 17.9 % ; P = .005 ; post hoc analysis ) owing to a lower placebo response rate than patients with C-reactive protein levels of less than 10 mg/L. Adverse events were similar among groups . CONCLUSIONS Certolizumab 400 mg may be effective and is well tolerated in patients with active Crohn 's disease . High placebo response rates in the large patient subgroup with low C-reactive protein levels may have obscured statistical separation between certolizumab and placebo . Ongoing phase III trials are necessary to establish the clinical efficacy of certolizumab Background : Certolizumab pegol ( Cimzia , CZP ) was approved for the treatment of Crohn 's disease ( CD ) patients in 2007 in Switzerl and as the first country worldwide . This prospect i ve phase IV study aim ed to evaluate the efficacy and safety of CZP over 26 weeks in a multicenter cohort of practice ‐based patients . Methods : Evaluation question naires at baseline , week 6 , and week 26 were completed by gastroenterologists in hospitals and private practice s. Adverse events were evaluated according to World Health Organization ( WHO ) guidelines . Results : Sixty patients ( 38F/22 M ) were included ; 53 % had complicated disease ( stricturing or penetrating ) , 45 % had undergone prior CD‐related surgery . All patients had prior exposure to systemic steroids , 96 % to immunomodulators , 73 % to infliximab , and 43 % to adalimumab . A significant decrease of the Harvey‐Bradshaw Index ( HBI ) was observed under CZP therapy ( 12.2 ± 4.9 at week 0 versus 6.3 ± 4.7 at week 6 and 6.7 ± 5.3 at week 26 , both P < 0.001 ) . Response and remission rates were 70 % and 40 % ( week 6 ) and 67 % and 36 % , respectively ( week 26 ) . The complete perianal fistula closure rate was 36 % at week 6 and 55 % at week 26 . The frequency of adverse drug reactions attributed to CZP was 5 % . CZP was continued in 88 % of patients beyond week 6 and in 67 % beyond week 26 . Conclusions : In a population of CD patients with predominantly complicated disease behavior , CZP proved to be effective in induction and maintenance of response and remission . This series provides the first evidence of CZP 's effectiveness in perianal fistulizing CD in clinical practice . ( Inflamm Bowel Dis 2011 ; BACKGROUND Certolizumab pegol is a pegylated humanized Fab ' fragment that binds tumor necrosis factor alpha . METHODS In a r and omized , double-blind , placebo-controlled trial , we evaluated the efficacy of certolizumab pegol in 662 adults with moderate-to-severe Crohn 's disease . Patients were stratified according to baseline levels of C-reactive protein ( CRP ) and were r and omly assigned to receive either 400 mg of certolizumab pegol or placebo subcutaneously at weeks 0 , 2 , and 4 and then every 4 weeks . Primary end points were the induction of a response at week 6 and a response at both weeks 6 and 26 . RESULTS Among patients with a baseline CRP level of at least 10 mg per liter , 37 % of patients in the certolizumab group had a response at week 6 , as compared with 26 % in the placebo group ( P=0.04 ) . At both weeks 6 and 26 , the corresponding values were 22 % and 12 % , respectively ( P=0.05 ) . In the overall population , response rates at week 6 were 35 % in the certolizumab group and 27 % in the placebo group ( P=0.02 ) ; at both weeks 6 and 26 , the response rates were 23 % and 16 % , respectively ( P=0.02 ) . At weeks 6 and 26 , the rates of remission in the two groups did not differ significantly ( P=0.17 ) . Serious adverse events were reported in 10 % of patients in the certolizumab group and 7 % of those in the placebo group ; serious infections were reported in 2 % and less than 1 % , respectively . In the certolizumab group , antibodies to the drug developed in 8 % of patients , and antinuclear antibodies developed in 2 % . CONCLUSIONS In patients with moderate-to-severe Crohn 's disease , induction and maintenance therapy with certolizumab pegol was associated with a modest improvement in response rates , as compared with placebo , but with no significant improvement in remission rates . ( Clinical Trials.gov number , NCT00152490 [ Clinical Trials.gov ] . ) |
10,368 | 26,322,669 | This meta- analysis shows no significant association between HIV positivity and PIH , pre-eclampsia , or eclampsia . | BACKGROUND There are data to suggest that infection with HIV or use of highly active antiretroviral therapy increases the risk of hypertensive disorders in pregnancy .
This systematic review and meta- analysis aims to provide an overview of the research hitherto . | 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 : Risk factors associated with preeclampsia in HIV-infected women remain largely unknown . Systemic angiogenic imbalance contributes to preeclampsia in HIV-uninfected women , but changes in angiogenic markers after highly active antiretroviral therapy ( HAART ) initiation have not been studied . Methods : The Mma Bana study r and omized 560 HIV-infected , HAART-naive pregnant women with CD4 counts ≥200 cells per cubic millimeter between 26 and 34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine or abacavir/zidovudine/lamivudine . Another 170 participants with CD4 counts less than 200 cells per cubic millimeter initiated nevirapine/zidovudine/lamivudine between 18 and 34 weeks gestation . Characteristics of 11 women who developed preeclampsia were compared with the remaining 722 Mma Bana participants who delivered using logistic regression . Plasma sample s drawn at HAART initiation and 1 month later from 60 women without preeclampsia and at HAART initiation for all 11 preeclamptic women were assayed for placental growth factor ( PlGF ) and soluble FMS toll-like tyrosine kinase-1 ( sFlt-1 ) . Results : Pre-HAART viral load greater than 100,000 copies per milliliter was associated with preeclampsia ( odds ratio : 5.8 , 95 % confidence interval : 1.8 to 19.4 , P = 0.004 ) . Median pre-HAART PlGF level was lower and sFlt-1 was higher in women who developed preeclampsia vs those who did not ( 130 vs 992 pg/mL , P = 0.001 ; 17.5 vs 9.4 pg/mL , P = 0.03 , respectively ) . In multivariate analysis , PlGF and viral load remained significantly associated with preeclampsia . No significant changes in angiogenic factors were noted after 1 month of HAART treatment among non-preeclamptic women . Conclusions : Pre-HAART viral load greater than 100,000 copies per milliliter and PlGF predicted preeclampsia among women starting HAART in pregnancy . Among non-preeclamptic women , HAART treatment did not significantly alter levels of PlGF or sFlt-1 after 1 month of treatment Purpose To compare the outcome of pregnancy between HIV positive pregnant women on highly active antiretroviral therapy ( HAART ) and HIV negative controls . Methods A prospect i ve matched case – control study . Results HIV positive women were significantly more likely to have anaemia in pregnancy [ p < 0.001 , odds ratio ( 95 % CI ) 5.66 ( 3.0–10.5 ) ] , intrauterine growth restriction [ p = 0.002 , odds ratio ( 95%CI ) 13.82 ( 1.8–106.7 ) ] , preterm labour [ p = 0.03 , odds ratio ( 95 % CI ) 2.89 ( 1.2–7.0 ) ] and birth weight less than 2,500 g [ p < 0.0001 , odds ratio ( 95 % CI ) 5.43 ( 2.4–12.0 ) ] . The 5-min apgar score less than 7 , admission into neonatal unit , stillbirth and perinatal mortality were comparable between the two groups . Conclusion Anaemia in pregnancy , intrauterine growth restriction , preterm labour and birth weight less than 2,500 g are important complications among HIV positive pregnant women . This information is vital for strategic antenatal care planning to improve obstetric and perinatal outcome in these women Abstract Objective : To estimate and interpret time trends in vertical transmission rates for HIV using data from national obstetric and paediatric surveillance registers . Design : Prospect i ve study of HIV infected women reported through obstetric surveillance . HIV infection status of the child and onset of AIDS were reported through paediatric surveillance . Rates of vertical transmission and progression to AIDS rate were estimated by methods that take account of incomplete follow up of children with indeterminate infection status and delay in AIDS reporting . Setting : British Isles . Subjects : Pregnant women infected with HIV whose infection was diagnosed before delivery , and their babies . Main outcome measures : Mother to child transmission of infection and progression to AIDS in children . Results : By January 1999 , 800 children born to diagnosed HIV infected women who had not breast fed had been reported . Vertical transmission rates rose to 19.6 % ( 95 % confidence interval 8.0 % to 32.5 % ) in 1993 before falling to 2.2 % ( 0 % to 7.8 % ) in 1998 . Between 1995 and 1998 use of antiretroviral treatment increased significantly each year , reaching 97 % of live births in 1998 . The rate of elective caesarean section remained constant , at around 40 % , up to 1997 but increased to 62 % in 1998 . Caesarean section and antiretroviral treatment together were estimated to reduce risk of transmission from 31.6 % ( 13.6 % to 52.2 % ) to 4.2 % ( 0.8 % to 8.5 % ) . The proportion of infected children developing AIDS in the first 6 months fell from 17.7 % ( 6.8 % to 30.8 % ) before 1994 to 7.2 % ( 0 % to 15.7 % ) after , coinciding with increased use of prophylaxis against Pneumocystis carinii pneumonia . Conclusions : In the British Isles both HIV related morbidity and vertical transmission are being reduced through increased use of interventions Key messages Reliable estimates of HIV vertical transmission rates can be derived from surveillance data Infected pregnant women are increasingly taking up elective caesarean section and antiretroviral treatment to reduce the risk of transmitting HIV to their babies Vertical transmission rates have fallen greatly over the past four years and progression to AIDS among infected children may also have slowed These benefits can occur only if infected women are diagnosed before or during OBJECTIVE : In view of recent suggestions that human immunodeficiency virus ( HIV ) infection may protect against preeclampsia , this study was done to evaluate whether untreated HIV-positive pregnant women have a lower rate of preeclampsia-eclampsia than HIV-negative women . METHODS : Subjects for this study were pregnant women from Soweto , South Africa , who gave birth from March to December 2002 at midwife-run clinics or at the Chris Hani Baragwanath Hospital and in whom the HIV status was known . A sample size calculation indicated that 2,588 subjects would be required to show statistical significance at P < .05 with a power of 80 % for a reduction in the rate of preeclampsia from 8 % to 5 % with HIV seropositivity , assuming an HIV seroprevalence rate of 30 % . Data collection was by record review from r and omly selected patient files and birth registers . RESULTS : In the total sample of 2,600 women , 1,797 gave birth at the hospital and 803 at the midwife-run clinics . The HIV seroprevalence rate was 27.1 % . Hypertension was found in 17.3 % of women , with 5.3 % having preeclampsia-eclampsia . The rates of preeclampsia-eclampsia were 5.2 % in HIV-negative and 5.7 % in HIV-positive women ( P = .61 ) . CD4 count results were available for only 13 women ( 0.5 % ) . CONCLUSION : Human immunodeficiency virus seropositivity was not associated with any reduction in the risk of developing preeclampsia-eclampsia . LEVEL OF EVIDENCE : OBJECTIVE We assessed the effect of prenatal and peripartum antibiotics on maternal morbidity and mortality among HIV-infected and uninfected women . METHODS A multicenter trial was conducted at clinical sites in 4 Sub-Saharan African cities : Blantyre and Lilongwe , Malawi ; Dar es Salaam , Tanzania ; and Lusaka , Zambia . A total of 1558 HIV-infected and 271 uninfected pregnant women who were eligible to receive both the prenatal and peripartum antibiotic/placebo regimens were enrolled . Pregnant women were interviewed at 20 - 24 weeks of gestation and a physical examination was performed . Women were r and omized to receive either antibiotics or placebo . At the 26 - 30 week visit , participants were given antibiotics or placebo to be taken every 4 hours beginning at the onset of labor and continuing after delivery 3 times a day until a 1-week course was completed . Logistic regression and Cox proportional hazards models were used . RESULTS There were no significant differences between the antibiotic and placebo groups for medical conditions , obstetric complications , physical examination findings , puerperal sepsis , and death in either the HIV-infected or the uninfected cohort . CONCLUSION Administration of study antibiotics during pregnancy had no effect on maternal morbidity and mortality among HIV-infected and uninfected pregnant women BACKGROUND Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy ( HAART ) . Although most HIV-1-infected individuals live in re source -constrained countries , there is little information about the frequency of hematological abnormalities such as anemia , neutropenia , and thrombocytopenia among individuals with advanced HIV-1 disease . METHODS This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a r and omized trial of antiretroviral efficacy in Africa , Asia , South America , the Caribbean , and the USA . Potential covariates for anemia , neutropenia , and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition . RESULTS The frequencies of neutropenia ( absolute neutrophil count ≤1.3 × 10⁹/l ) , anemia ( hemoglobin ≤10g/dl ) , and thrombocytopenia ( platelets ≤125 × 10⁹/l ) at initiation of antiretroviral therapy were 14 % , 12 % , and 7 % , respectively , and varied by country ( p<0.0001 for each ) . In multivariable models , anemia was associated with gender , platelet count , and country ; neutropenia was associated with CD4 + lymphocyte and platelet counts ; and thrombocytopenia was associated with country , gender , and chronic hepatitis B infection . CONCLUSIONS Differences in the frequency of pretreatment hematological abnormalities could have important implication s for the choice of antiretroviral regimen in re source -constrained setting AIM The aim of the study was to compare HIV positive and negative pregnant women with respect to maternal and neonatal outcome to inform the development of clinical practice guidelines . BACKGROUND HIV infection in pregnancy places an added burden on the physical ability of the woman 's body to cope with pregnancy . As a result HIV causes an exaggeration of the problems related to pregnancy . METHOD Data were collected by means of a retrospective record review conducted on 212 stratified r and omly selected HIV positive and 101 matched HIV negative pregnant women . The two sample t-test and Fisher exact test were used to compare the maternal and neonatal outcomes of HIV positive and negative pregnant women . RESULTS HIV positive pregnant women had a significantly lower haemoglobin ( 10.85 vs. 11.48 g/dl ; P = 0.001 ) , attended significantly fewer antenatal clinic appointments ( 4.03 vs. 4.63 ; P = 0.04 ) , weighed significantly less ( 72.07 vs. 76.69 kg ; P = 0.02 ) and were significantly more likely to present with an abnormal vaginal discharge ( 32.55 vs. 24.75 % ; P = 0.02 ) than HIV negative pregnant women . The difference in the prevalence in HIV positive pregnant women of pregnancy induced hypertension ( 16.98 vs. 9.90 % ; P = 0.06 ) , syphilis infection ( 5.95 vs. 0.99 % ; P = 0.062 ) and urinary tract infection ( 15.53 vs. 7.92 % ; P = 0.06 ) approached significance when compared with HIV negative pregnant women . HIV positive pregnant women were significantly more likely to present with intrauterine growth retardation ( 4.72 vs. 0 % ; P = 0.03 ) , significantly more likely to deliver earlier ( 37.92 vs. 38.51 weeks ; P = 0.03 ) and significantly more likely to deliver neonates weighing less ( 2969.98 vs. 3138.43 g ; P = 0.01 ) than HIV negative pregnant women . CONCLUSION The Department of Health attributes the high rate of HIV and AIDS related maternal morbidity and mortality in South Africa to the absence of accepted and practical guidelines for midwives ' antenatal assessment and management of HIV positive pregnant women . Relevance to clinical practice . This study identifies maternal and neonatal outcomes related to HIV infection in pregnancy and provides evidence required to inform the development of clinical practice guidelines The aim of this study is to evaluate the characteristics of pregnant women whether they are HIV infected or not and their prenatal care . It is a cross-sectional study . HIV-infected women were derived from a cohort study of all HIV-infected pregnant women followed from 1995 to 2005 , at the Instituto de Puericultura e Pediatria Martagão Gesteira – Rio de Janeiro . HIV-non-infected women were derived from a r and om sample of all pregnant women who gave birth at Rio de Janeiro municipality between 1999 and 2001 . All relevant sociodemographic , clinical , and pregnancy outcomes data were retrieved from both studies . To evaluate the prenatal care , we calculated the Kotelchuck Modified Index ( KMI ) . The index is based on the months of initiation of prenatal care and the proportion of visits observed in each trimester , according to gestational age at birth . Comparisons were performed using Student t- and chi-square tests . Variables with p-value < 0.25 were included in an unconditional logistic regression model . There were 713 HIV-infected women and 2145 HIV-non-infected women . Variables independently associated with HIV status were : inadequate KMI ( OR=4.08 , 95 % CI=3.17–5.24 ) ; lower educational level ( OR=1.32 , 95 % CI=1.04–1.68 ) ; does not live with a partner ( OR=3.54 , 95 % CI=2.66–4.64 ) ; lower family income ( OR=4.71 , 95 % CI=3.62–6.14 ) ; tobacco use ( OR=2.17 , 95 % CI=1.63–2.88 ) ; and hypertension ( OR=1.47 , 95 % CI=1.01–2.17 ) . Prematurity was not independently associated with HIV status . Although in Brazil , the HIV care is free of charge , pregnant women are still having difficulty to reach the specialized care . Better access to care must be offered to this population and studies of prematurity in the HIV-infected women must evaluate their prenatal care Between January 1993 and January 1995 , a prospect i ve case-control hospital-based study was done in ninety-two HIV seropositive and 173 HIV seronegative mothers for pregnancy outcome and complications associated with the pregnancy in G and hi Memorial Hospital , Addis Ababa , Ethiopia . The serostatus and seroconversion in the children born to the seropositive women was also assessed . The study showed that there was a significant difference in birthweight ( p < 0.001 ) , puerperal infections ( p < 0.0001 ) , duration of pregnancy ( p < 0.001 ) , and fifth minute APGAR score ( p < 0.001 ) in the two groups of the study population . The study further indicated that the seroprevalence in the pregnant women was 20.4 % and vertical transmission rate at 18 months was 68.5 % . From the study one can conclude that HIV seropositivity adversely affects pregnancy out come OBJECTIVE To determine whether pre-eclampsia and gestational hypertension are less common in HIV infected women . METHODS This prospect i ve cohort study was performed in the Western Cape province of South Africa . HIV negative and positive pregnant women without chronic renal or chronic hypertensive disease were continuously recruited . During the study period HIV positive patients received either mono- or triple ( HAART ) antiretroviral therapy for prevention of vertical transmission or maternal care . Only routine clinical management was performed . The development of hypertensive disease during pregnancy was recorded . RESULTS 1093 HIV positive and 1173 HIV negative cases were identified during pregnancy and evaluated again after delivery . Significantly fewer cases of pre-eclampsia n=35 ( 3.2 % ) were recorded in the HIV positive group than in the HIV negative group , n=57 ( 4.9 % ) ( p=0.045 ; OR 0.65 95 % CI 0.42 - 0.99 ) . There were also significantly fewer cases of gestational hypertension recorded in the HIV positive group compared to the HIV negative group ( p=0.026 ; OR 0.53 95 % CI 0.30 - 0.94 ) . Multiple logistic regression analysis confirmed the reductive effect of HIV on pre-eclampsia and gestational hypertension . CONCLUSION Pre-eclampsia and gestational hypertension are less common in HIV infected women being managed with mono- or triple anti-retroviral therapy Little is known about birth outcomes for HIV-infected women in India . We examine maternal and neonatal birth outcomes in HIV-infected women within the context of enhanced pre-natal care associated with a r and omized clinical trial conducted in Pune , India . Birth outcomes of 212 HIV-infected pregnant women were compared with those of 130 HIV-uninfected pregnant women attending a government tertiary care hospital between 2002 and 2004 . These women and children were participating in the Six Week Extended-Dose Nevirapine ( SWEN ) study . Birth outcomes and maternal morbidity data were collected at delivery . We found no differences between HIV-infected and uninfected pregnant women with respect to the proportion with elevated intrapartum blood pressure , eclampsia , oligohydramnios , intrauterine growth restriction ( IUGR ) , preterm delivery , or caesarean section ( p>0.05 ) . HIV-infected women were more likely to have peri-partum fever ( 3 % versus 0 % , p=0.04 ) . There were no differences in neonatal parameters such as low birth weight ( LBW ) , infants who were small for gestational age , or those having congenital anomalies ( p>0.05 ) . Compared with infants of HIV-infected women enrolled antenatally , infants of HIV-infected women enrolled in the post-partum ward had a higher risk of pre-term delivery ( 20 % versus 8 % , p=0.02 ) and LBW ( 41 % versus 22 % , p=0.002 ) . HIV-infected women in this cohort in India were not found to have significant negative birth outcomes . Antenatal care was important as those not having received any antenatal care prior to deliver were at increased risk of having a pre-term delivery or an infant with LBW . Based on these data , regular antenatal care provided to HIV-infected women can reduce risk of adverse birth outcomes for their infants |
10,369 | 25,636,589 | This meta- analysis demonstrates that proliferative benign breast disease with or without atypia is associated with a significant increase in risk of developing breast cancer . | Abstract Benign breast disease ( BBD ) is a broad category of diagnoses reported to convey a variable degree of increased risk of developing breast cancer .
A meta- analysis of the existing literature was performed to quantify the risk estimate associated with BBD . | Background Exercise is a modifiable factor that is inversely related to risk for breast cancer . To determine if physical activity has a preventative effect on development of premalignant breast lesions , we examined the association between exercise and the incidence of proliferative benign breast disease . Methods In 1997 , the Nurses ’ Health Study II cohort reported levels of physical activity during adolescence and adulthood using a vali date d recall instrument . We followed 40,318 participants free from benign breast disease ( BBD ) or cancer prospect ively for four years and confirmed 232 proliferative benign breast lesions by central ized pathology review . Cox proportional hazards models estimated the age-adjusted and multivariable-adjusted relative risks for physical activity and proliferative benign breast disease . Results We observed a significant inverse association for walking and incidence of BBD , risk was reduced by 9 % per hour of walking ( 95 % CI 0 % to 17 % ) , ( p trend = 0.05 ) . Despite a small number of cases , risk of columnar cell lesions also suggested an inverse association with strenuous activity ( RR for 4 or more hours of strenuous activity per week = 0.62 ; 0.31–1.22 compared to < 1 h per week ) . Conclusions This study suggests that exercise may be inversely associated with the risk of developing proliferative benign breast disease , one of the earliest steps in the development of breast cancer BACKGROUND The risk of invasive breast cancer associated with benign breast disease ( BBD ) other than atypical hyperplasia and in situ breast cancer , especially with nonproliferative diagnosis , has not been explored extensively . This report evaluates the risk of breast cancer associated with this lower-category BBD ( LC-BBD ) . METHODS 11 307 women without prior history of atypical hyperplasia or in situ breast cancer at r and omization ( 1992 - 1997 ) were identified from the cohort of the National Surgical Adjuvant Breast and Bowel Project 's Breast Cancer Prevention Trial . Pathologic findings from breast biopsy reports through August 2002 were review ed , and Cox proportional hazards models were used to determine the relative risks ( RRs ) of breast cancer with 95 % confidence intervals ( CIs ) . The relative risks of breast cancer for LC-BBD were adjusted for treatment and for breast cancer risk as determined by the modified Gail model . RESULTS Of the 11 307 women , 1376 had LC-BBD , of whom 47 developed breast cancer , and of the 9931 women without LC-BBD , 291 developed breast cancer . The RR of breast cancer for women with LC-BBD relative to women without LC-BBD was 1.60 ( 95 % CI = 1.17 to 2.19 ) . Among women 50 years of age and older , the RR of breast cancer for those with LC-BBD was 1.95 ( 95 % CI = 1.29 to 2.93 ) . After adjustment for treatment and breast cancer risk , the RR of breast cancer for women with LC-BBD was 1.41 ( 95 % CI = 1.03 to 1.94 ) . CONCLUSIONS Women with LC-BBD had a statistically significant increased risk of breast cancer . The elevation of breast cancer risk was especially evident in women 50 years of age and older . Furthermore , this risk was independent of that associated with key epidemiologic breast cancer risk factors Specific histologic types of benign breast disease ( BBD ) may increase breast cancer risk . The authors analyzed data from a population ‐based , case‐control study of women aged 20 to 54 with newly diagnosed breast cancer and control subjects r and omly selected from the general population . A panel of pathologists classified the histologic findings of biopsy slides for 433 women with breast cancer and 261 control subjects , all of whom had a history of biopsy for BBD , as to the presence of epithelial hyperplasia , atypia , and other histologic features . When compared with women who had never had a breast biopsy , women with BBD without hyperplasia had an odds ratio of 1.5 ( 95 % confidence limits [ CL ] 1.3 to 1.9 ) , women with hyperplasia without atypia had an odds ratio of 1.8 ( CL = 1.3 , 2.4 ) , and women with hyperplasia and atypia had an odds ratio of 2.6 ( CL = 1.6 , 4.1 ) . Fibroadenoma was an independent risk factor for breast cancer ( odds ratio = 1.7 ; CL = 1.1 , 2.5 ) . These findings suggest that women with BBD with epithelial hyperplasia either with or without atypia and women with fibroadenoma should be monitored carefully because of their elevated risk for breast cancer . Cancer 1992 ; 69:1408‐1414 Objective We examined the association between adolescent fiber intake and proliferative BBD , a marker of increased breast cancer risk , in the Nurses ’ Health Study II . Methods Among 29,480 women who completed a high school diet question naire in 1998 , 682 proliferative BBD cases were identified and confirmed by central ized pathology review between 1991 and 2001 . Multivariate-adjusted Cox proportional hazards regression was used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . Results Women in the highest quintile of adolescent fiber intake had a 25 % lower risk of proliferative BBD ( multivariate HR ( 95 % CI ) : 0.75 ( 0.59 , 0.96 ) , p-trend = 0.01 ) than women in the lowest quintile . High school intake of nuts was also related to significantly reduced BBD risk . Women consuming ≥2 servings of nuts/week had a 36 % lower risk ( multivariate HR ( 95 % CI ) : 0.64 ( 0.48 , 0.85 ) , p-trend < 0.01 ) than women consuming < 1 serving/month . Results were essentially the same when the analysis was restricted to prospect i ve cases ( n = 142 ) diagnosed after return of the high school diet question naire . Conclusions These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influences subsequent risk of breast disease and may suggest a viable means for breast cancer prevention OBJECTIVE : To investigate prospect ively , using alcoholic beverage consumption data collected in real time , the association between adolescent drinking and risk of biopsy-confirmed benign breast disease ( BBD ) in young women . PARTICIPANTS AND METHODS : The Growing Up Today Study is a prospect i ve cohort study of US girls , aged 9 to 15 years at baseline , with annual question naires from 1996 through 2001 , followed by question naires in 2003 , 2005 , and 2007 . On the 2003 survey , the participants ( then aged 16–23 years ) provided information about their alcoholic beverage consumption in the previous year . On the 2005 and 2007 surveys , a total of 6899 women ( aged 18–27 years ) reported whether a health care provider had ever diagnosed them with BBD ( n = 147 cases ) and whether it was confirmed by biopsy ( n = 67 cases ) ; 6752 women reported never being diagnosed with BBD . RESULTS : Adjusted for age and BMI , quantity of alcohol consumed was associated with increased risk of biopsy-confirmed BBD ( odds ratio : 1.50 per drink per day [ 95 % confidence interval : 1.19–1.90 ] ) . Girls who typically drank 6 or 7 days/week were at higher risk ( odds ratio : 5.50 [ 95 % confidence interval : 1.23–24.53 ] ) compared with those who never drank or who drank less than once per week . CONCLUSIONS : Higher amounts consumed , and more frequent consumption , of alcoholic beverages in adolescence may increase the occurrence of BBD in young women . Advising teenagers to avoid alcoholic beverages , along with smoking and sun exposure , may reduce cancer incidence in adulthood Background Data from the Shanghai Breast Cancer Study were analyzed to evaluate the relationship between benign breast disease ( BBD ) and breast cancer among Chinese women with a self-report of physician-diagnosed BBD . Methods Study participants consisted of 3,452 breast cancer cases and 3,474 population controls recruited by the Shanghai Breast Cancer Study . In-person interviews were conducted to collect information on demographics and suspected risk factors for breast cancer , including a detailed history of BBD . Unconditional logistic regression was used to derive adjusted odds ratios ( ORadj ) and 95 % confidence intervals ( CI ) for the association between self-reported BBD and breast cancer . Results Women with breast cancer were significantly more likely to have a self-reported history of BBD including lobular proliferation ( ORadj = 1.6 ; 95 % CI 1.4–1.8 ) , fibroadenoma ( ORadj = 1.9 ; 95 % CI 1.6–2.3 ) , and other BBD ( ORadj = 1.6 ; 95 % CI 1.3–2.1 ) . Breast cancer risk was lower for surgically treated fibroadenoma as compared to non-surgically treated and higher for other BBDs that were surgically treated versus non-surgically treated . Conclusions Our results suggest that personal history of BBD is associated with an increased risk of future breast cancer among women in China . Surgical intervention for fibroadenoma may reduce the risk In adult women with retrospective data , childhood adiposity , pubertal growth and development were associated with benign breast disease ( BBD ) and /or breast cancer . The authors prospect ively evaluated these childhood/adolescent characteristics and BBD risk |
10,370 | 26,855,711 | Conclusions There is considerable scientific evidence describing the programs for smoking cessation used in dentistry , which support their effectiveness . | Introduction Smoking is one of the main public health problems in developed countries .
Despite extensive evidence on the effects of smoking on both oral and general health , the rate of smoking cessation is not promising .
Material and Methods To review the evidence on knowledge and programs for smoking cessation developed by dentists , a literature review was carried out on programs for smoking cessation from the dentist ’s perspective , as well as a review of behavioral guidelines that have been recently proposed for these interventions . | INTRODUCTION Tobacco use is a global health care problem . Repetitive exposure to nicotine produces neuroadaptation result ing in nicotine dependence . Smoking is associated with a range of diseases , causing high levels of morbidity and mortality and is one of the leading causes of preventable deaths , with more than 4.6 million smokers worldwide dying each year from smoking related illnesses . Stopping smoking has major health benefits . Quitting at any age provides both short and long term benefits . MATERIAL S AND METHODS 45 patients attending the outpatient department at the Oxford Dental College , Bangalore , were r and omly allocated to three groups of interventions namely placebo , counseling and nicotine replacement therapy ( NRT ) . Initially each one was assessed for carbon monoxide levels using a breath analyser ( pico smokerlyser bedfont UK ) . They were followed up for six months and the carbon monoxide levels were again assessed using the same instrument . The paired t test was used to compare the results before and after the intervention . RESULTS The scores before the initiation of intervention and after treatment were compared and all three interventions were found to be statistically significant after six months . It was noticed that patients with very low or low dependence followed by high dependence had good response in the placebo group ( 68 % and 47.6 % respectively ) , in the counseling group maximum response was seen in the medium followed by the very low group ( 61 % and 59 % respectively ) , and maximum response was seen in very high followed by the very low group with NRT ( 78.7 % and 60.5 % respectively ) . CONCLUSION The inference that can be drawn from the present study is that non-invasive , non pharmacological methods like placebo and counseling are effective in low to medium groups , and NRT is effective with higher nicotine dependence Background Tobacco is still the number one life style risk factor for ill health and premature death and also one of the major contributors to oral problems and diseases . Dentistry may be a potential setting for several aspects of clinical public health interventions and there is a growing interest in several countries to develop tobacco cessation support in dentistry setting . The aim of the present study was to assess the relative effectiveness of a high intensity intervention compared with a low intensity intervention for smoking cessation support in a dental clinic setting . Methods 300 smokers attending dental or general health care were r and omly assigned to two arms and referred to the local dental clinic for smoking cessation support . One arm received support with low intensity treatment ( LIT ) , whereas the other group was assigned to high intensity treatment ( HIT ) support . The main outcome measures included self-reported point prevalence and continuous abstinence ( ≥ 183 days ) at the 12-month follow-up . Results Follow-up question naires were returned from 86 % of the participants . People in the HIT-arm were twice as likely to report continuous abstinence compared with the LIT-arm ( 18 % vs. 9 % , p = 0.02 ) . There was a difference ( not significant ) between the arms in point prevalence abstinence in favour of the HIT- protocol ( 23 % vs. 16 % ) . However , point prevalence cessation rates in the LIT-arm reporting additional support were relatively high ( 23 % ) compared with available data assessing abstinence in smokers trying to quit without professional support . ConclusionS creening for willingness to quit smoking within the health care system and offering smoking cessation support within dentistry may be an effective model for smoking cessation support in Sweden . The LIT approach is less expensive and time consuming and may be appropriate as a first treatment option , but should be integrated with other forms of available support in the community . The more extensive and expensive HIT- protocol should be offered to those who are unable to quit with the LIT approach in combination with other support . Trial Registration Trial registration number : BACKGROUND The efficacy of pharmacotherapy for smoking cessation is well documented . However , due to relapse rates and side effects , hypnotherapy is gaining attention as an alternative treatment option . The aim of this one-center r and omized study was to compare the efficacy of hypnotherapy alone , as well as hypnotherapy with nicotine replacement therapy ( NRT ) , to conventional NRT in patients hospitalized with a cardiac or pulmonary illness . METHODS We evaluated self-reported and biochemically verified 7-day prevalence smoking abstinence rates at 12 and 26 weeks post-hospitalization . Patients ( n=164 ) were r and omized into one of three counseling-based treatment groups : NRT for 30 days ( NRT ; n=41 ) , a 90-min hypnotherapy session ( H ; n=39 ) , and NRT with hypnotherapy ( HNRT ; n=37 ) . Treatment groups were compared to a " self-quit " group of 35 patients who refused intervention . RESULTS Hypnotherapy patients were more likely than NRT patients to be nonsmokers at 12 weeks ( 43.9 % vs. 28.2 % ; p=0.14 ) and 26 weeks after hospitalization ( 36.6 % vs. 18.0 % ; p=0.06 ) . Smoking abstinence rates in the HNRT group were similar to the H group . There was no difference in smoking abstinence rates at 26 weeks between " self quit " and participants in any of the treatment groups . In multivariable regression analysis adjusting for diagnosis and demographic characteristics , H and HNRT were over three times more likely than NRT participants to abstain at 26-weeks post-discharge ( RR=3.6 ; p=0.03 and RR=3.2 ; p=0.04 , respectively ) . CONCLUSION Hypnotherapy is more effective than NRT in improving smoking abstinence in patients hospitalized for a smoking-related illness , and could be an asset to post-discharge smoking cessation programs |
10,371 | 25,188,542 | Our results are counter-intuitive at first instance , but some other authors have found the same results .
In the preparation of this editorial , we found a lack of research in patients who started drinking excessive amounts of alcohol very late in life .
This is in contrast with , for example , a fair amount of research in LOD and at least some research in LOS | In this issue of International Psychogeriatrics , our research group published a paper on alcohol use disorders ( AUD ) in elderly adults ( Kist et al. , 2014 ) .
According to different authors , age of onset is an important characteristic to distinguish subgroups of patients with AUD , similar to , for example , late-onset depression ( LOD ) and late-onset schizophrenia ( LOS ) .
However , in AUD , many patients started having alcohol problems much later in life , for example , after 45 , 50 , or even after 60 years .
These very late onset patients are almost completely ignored in research . | OBJECTIVE The authors sought to determine whether integrated mental health services or enhanced referral to specialty mental health clinics results in greater engagement in mental health/substance abuse services by older primary care patients . METHOD This multisite r and omized trial included 10 sites consisting of primary care and specialty mental health/substance abuse clinics . Primary care patients 65 years old or older ( N=24,930 ) were screened . The final study group consisted of 2,022 patients ( mean age=73.5 years ; 26 % female ; 48 % ethnic minority ) with depression ( N=1,390 ) , anxiety ( N=70 ) , at-risk alcohol use ( N=414 ) , or dual diagnosis ( N=148 ) who were r and omly assigned to integrated care ( mental health and substance abuse providers co-located in primary care ; N=999 ) or enhanced referral to specialty mental health/substance abuse clinics ( i.e. , facilitated scheduling , transportation , payment ; N=1,023 ) . RESULTS Seventy-one percent of patients engaged in treatment in the integrated model compared with 49 % in the enhanced referral model . Integrated care was associated with more mental health and substance abuse visits per patient ( mean=3.04 ) relative to enhanced referral ( mean=1.91 ) . Overall , greater engagement was predicted by integrated care and higher mental distress . For depression , greater engagement was predicted by integrated care and more severe depression . For at-risk alcohol users , greater engagement was predicted by integrated care and more severe problem drinking . For all conditions , greater engagement was associated with closer proximity of mental health/substance abuse services to primary care . CONCLUSIONS Older primary care patients are more likely to accept collaborative mental health treatment within primary care than in mental health/substance abuse clinics . These results suggest that integrated service arrangements improve access to mental health and substance abuse services for older adults who underuse these services The purpose of this study was to examine the impact of the Unified Psychogeriatric Biopsychosocial Evaluation and Treatment ( UPBEAT ) Program , an interdisciplinary mental health care management program , on the behavioral health symptoms of elderly veterans . Participants , 60 years and older , included 2637 veterans recruited from medical/surgical units who screened positively for significant depressive or anxiety symptoms and /or at-risk alcohol drinking . Participants were r and omized to UPBEAT or to usual care . Primary outcomes were measured at baseline and at 6 , 12 , and 24 months . Participant nonadherence to the protocol was common and is a major limitation . There were no differences between UPBEAT and usual care patients on symptom or functional outcomes at any follow-up point . Exploratory analyses suggested that among participants with more physical health problems , there were greater improvements in depressive symptoms in those assigned to UPBEAT care . Despite a theoretical and practically sound intervention , participation was low and treatment outcomes , while generally good , appeared unaffected by the addition of the program The purpose of the study was to compare the effectiveness of programmed and intensified intervention on lifestyle changes , including physical activity , cigarette smoking , alcohol consumption and diet , in patients aged ≥ 65 with the usual care of general practitioners ( GP ) . In this multicenter r and omized controlled trial , 738 patients aged ≥ 65 were r and omly assigned to receive intensified intervention ( N = 371 ) or usual care ( N = 367 ) of a GP for lifestyle changes , with 18-month follow-up . The main outcome measures were physical activity , smoking , alcohol consumption and diet . The study was conducted in 59 general practice s in Croatia between May 2008 and May 2010 . The patients ' mean age was 72.3 ± 5.2 years . Significant diet correction was achieved after 18-month follow-up in the intervention group , comparing to controls . More patients followed strictly Mediterranean diet and consumed healthy foods more frequently . There was no significant difference between the groups in physical activity , tobacco smoking and alcohol consumption or diet after the intervention . In conclusion , an 18-month intensified GP 's intervention had limited effect on lifestyle habits . GP intervention managed to change dietary habits in elderly population , which is encouraging since elderly population is very resistant regarding lifestyle habit changes . Clinical trial registration number . IS RCT N31857696 AIMS To examine whether a multi-faceted intervention among older at-risk drinking primary care patients reduced at-risk drinking and alcohol consumption at 3 and 12 months . DESIGN R and omized controlled trial . SETTING Three primary care sites in southern California . PARTICIPANTS Six hundred and thirty-one adults aged ≥ 55 years who were at-risk drinkers identified by the Comorbidity Alcohol Risk Evaluation Tool ( CARET ) were assigned r and omly between October 2004 and April 2007 during an office visit to receive a booklet on healthy behaviors or an intervention including a personalized report , booklet on alcohol and aging , drinking diary , advice from the primary care provider and telephone counseling from a health educator at 2 , 4 and 8 weeks . MEASUREMENTS The primary outcome was the proportion of participants meeting at-risk criteria , and secondary outcomes were number of drinks in past 7 days , heavy drinking ( four or more drinks in a day ) in the past 7 days and risk score . FINDINGS At 3 months , relative to controls , fewer intervention group participants were at-risk drinkers [ odds ratio ( OR ) 0.41 ; 95 % confidence interval ( CI ) 0.22 - 0.75 ] ; they reported drinking fewer drinks in the past 7 days [ rate ratio ( RR ) 0.79 ; 95 % CI 0.70 - 0.90 ] , less heavy drinking ( OR 0.46 ; 95 % CI 0.22 - 0.99 ) and had lower risk scores ( RR 0.77 95 % CI 0.63 - 0.94 ) . At 12 months , only the difference in number of drinks remained statistically significant ( RR 0.87 ; 95 % CI 0.76 - 0.99 ) . CONCLUSIONS A multi-faceted intervention among older at-risk drinkers in primary care does not reduce the proportions of at-risk or heavy drinkers , but does reduce amount of drinking at 12 months BACKGROUND Alcohol use in older adults is common . It is associated with depression , hypertension , diabetes , drug interactions , accidents , and increased rates of emergency department visits and hospitalizations . METHODS A controlled clinical trial ( Project GOAL --Guiding Older Adult Lifestyles ) tested the efficacy of brief physician advice in reducing the alcohol use and use of health care services of older adult problem drinkers . Twenty-four community-based primary care practice s in Wisconsin ( 43 family physicians and internists ) participated in the trial . Of the 6073 patients screened , 105 men and 53 women met inclusion criteria and were r and omized into a control group ( n = 71 ) or an intervention group ( n = 87 ) . Intervention group patients received two 10- to 15-minute physician-delivered counseling sessions that included advice , education , and contracting using a scripted workbook . A total of 146 patients ( 92.4 % ) participated in the 12-month follow-up procedure . RESULTS No significant differences were found between the control and intervention groups at baseline in alcohol use , age , socioeconomic status , depression , onset of alcohol use , smoking status , activity level , or use of mood-altering drugs . The older adults who received the physician intervention demonstrated a significant reduction in 7-day alcohol use , episodes of binge drinking , and frequency of excessive drinking ( P < .005 ) compared with the control group at 3 , 6 , and 12 months after the intervention . There was a 34 % reduction in 7-day alcohol use , 74 % reduction in mean number of binge-drinking episodes , and 62 % reduction in the percentage of older adults drinking more than 21 drinks per week in the intervention group compared with the control group . There were no significant changes in health status . Patterns of health care utilization were not extensively analyzed because of the small number of events . CONCLUSIONS This study provides the first direct evidence that brief physician advice can decrease alcohol use by older adults in community-based primary care practice Objectives The purpose of this study was to explore the efficacy in a primary care setting of a telephone-based disease management program for the acute management of depression and /or at-risk drinking . Material s and Methods Veterans ( N = 97 ) with depression and /or at-risk drinking were identified by systematic screening and assessment . Eligible subjects received either telephone disease management ( TDM ) program or usual care based on r and om assignment of their clinician . The TDM program consisted of regular contacts with each subject by a behavioral health specialist ( BHS ) to assist in assessment , education , support , and treatment planning . Symptomatic outcomes were assessed at 4 months . Results Overall response rates favored those assigned to TDM compared with those assigned to usual care ( 39.1 % responded vs. 17.6 % , p = 0.022 ) . Response rates within the separate diagnostic groups also favored TDM , but this was only significant for depressive disorders . Conclusions Although the sample size was modest and the sample was limited to veterans , findings strongly suggest that a telephone-based disease management program can improve outcomes for patients with a behavioral health problem . Findings also suggest that a health specialist can focus and manage patients with different diagnoses , thus exp and ing the role beyond just depression care . TDM may be a viable , low-cost , model for primary care clinicians to deliver manual guideline -adherent behavioral health care , especially in a VA clinical setting The authors examined the efficacy of naltrexone as an adjunctive treatment for alcohol dependence in older adults . Forty-four veterans over 50 years of age were enrolled in a 12-week , double-blind , placebo-controlled efficacy study of naltrexone ( the equivalent of 50 mg per day ) . There were no differences in the frequency of any self-reported adverse effects or in liver enzyme values between the placebo- and naltrexone-treated groups . There were no differences between the treatment groups in the number of subjects remaining abstinent or in the number of subjects who relapsed . However , all placebo-treated subjects relapsed after sampling alcohol , whereas only three of six naltrexone-treated subjects met relapse criteria after alcohol exposure ( P = 0.024 ) . The authors conclude that naltrexone was well tolerated and efficacious in preventing relapse in subjects who drank One hundred thirty-seven older alcoholic patients were r and omly assigned to two different inpatient treatment programs at a Veterans Affairs medical center and followed for one year after discharge . The older alcoholic rehabilitation ( OAR ) program was operated by a tolerant staff that specialized in treating elderly alcoholics . Treatment included reminiscence therapy with goals of developing patient self-esteem and peer relationships . The traditional care program emphasized confrontation to focus on patients ' past failures and present conflicts . Patient care costs were slightly lower ( 2.5 percent lower ) in the OAR program than in the more traditional program , and OAR patients were 2.1 times more likely to report abstinence at one year . Response to the OAR program was best for patients over 60 years of age OBJECTIVE Adherence to treatment has been demonstrated to be an important factor for remission from alcohol dependence . The authors compared therapy and medication adherence for treatment of alcohol dependence in older adults with adherence in younger adults . METHODS All subjects were participants in a r and omized , double-blind , placebo-controlled efficacy trial of naltrexone for the treatment of alcohol dependence . All subjects received a medically-based psychosocial intervention focused on motivating patients to change and on adherence to treatment . The therapy is nonconfrontational and is delivered by a nurse-practitioner . RESULTS Compared with younger adults , older adults had greater attendance at therapy sessions and greater adherence to the medication . Age-group was the only pretreatment factor associated with adherence . The greater adherence in older adults translated to less relapse than in younger adults . CONCLUSION Treatment for alcohol dependence can be effective for older adults . Older adults appear to respond well to a medically-oriented program that is supportive and individualized . In fact , findings from this study suggest that older adults can be treated in mixed-age treatment setting s when psychotherapeutic strategies are used that are age-appropriate and delivered on an individual basis OBJECTIVE The purpose of this study was to examine the effectiveness of a patient-provider educational intervention in reducing at-risk drinking among older adults . METHOD This was a cluster-r and omized controlled trial of 31 primary care providers and their patients ages 60 years and older at a community-based practice with seven clinics . Recruitment occurred from July 2005 to August 2007 . Eligibility was determined by telephone and a baseline mailed survey . A total of 1,186 at-risk drinkers were identified by the Comorbidity Alcohol Risk Evaluation Tool . Follow-up patient surveys were administered at 3 , 6 , and 12 months after baseline . Study physicians and their patients were r and omly assigned to usual care ( n = 640 patients ) versus the Project SHARE ( Senior Health and Alcohol Risk Education ) intervention ( n = 546 patients ) , which included personalized reports , educational material s , drinking diaries , physician advice during office visits , and telephone counseling delivered by a health educator . Main outcomes were alcohol consumption , at-risk drinking ( overall and by type ) , alcohol discussion s with physicians , health care utilization , and screening and intervention costs . RESULTS At 12 months , the intervention was significantly associated with an increase in alcohol-related discussion s with physicians ( 23 % vs. 13 % ; p ≤ .01 ) and reductions in at-risk drinking ( 56 % vs. 67 % ; p ≤ .01 ) , alcohol consumption ( -2.19 drinks per week ; p ≤ .01 ) , physician visits ( -1.14 visits ; p = .03 ) , emergency department visits ( 16 % vs. 25 % ; p ≤ .01 ) , and nonprofessional caregiving visits ( 12 % vs. 17 % ; p ≤ .01 ) . Average variable costs per patient were $ 31 for screening and $ 79 for intervention . CONCLUSIONS The intervention reduced alcohol consumption and at-risk drinking among older adults . Effects were sustained over a year and may have been associated with lower health care utilization , off setting screening and intervention costs We sought to determine if Brief Interventions [ BIs , Motivational Enhancement ( ME ) , and Brief Advice ( BA ) ] reduced alcohol consumption among hazardous alcohol drinking elderly ( 65 years or older ) and whether the elderly responded similarly to younger population s. In 12 primary care offices from 10 1995 to 12 1997 , we screened 13,438 patients of whom 2702 were elderly ( 180 were hazardous drinkers ) . Forty-five elderly enrollees were r and omized to receive ME ( n = 18 ) , BA ( n = 12 ) , and St and ard Care ( SC , n = 12 ) . At baseline , the elderly drank more alcohol and abstained fewer days than the younger cohort ( p<0.05 ) . During the year , the elderly in ME , BA , and SC intervention arms increased the number of days abstained , decreased the number of drinks per day , and reduced the number of total days per month drinking . There were trends toward decreases in the alcohol consumption measures in the ME and BA treatment arms compared to SC . The elderly 's response to all interventions was similar to that of the younger cohort . This study suggests that hazardous alcohol consumption in the elderly is common and that BIs reduce alcohol consumption in the elderly similar to younger population OBJECTIVES To evaluate whether providing physicians and older patients with personalized reports of drinking risks and benefits and patient education reduces alcohol-related risks and problems . DESIGN Prospect i ve comparison study . SETTING Community primary care . PARTICIPANTS Twenty-three physicians and 665 patients aged 65 and older . INTERVENTION Combined report , in which six physicians and 198 [ corrected ] patients received reports of patients ' drinking classifications and patients also received education ; patient report , in which 245 patients received reports and education , but their five physicians did not receive reports ; and usual care . MEASUREMENTS Assessment s at baseline and 12 months later to determine patients ' nonhazardous ( no known risks ) , hazardous ( risks for problems ) , or harmful ( presence of problems ) classifications using the Computerized Alcohol-Related Problems Survey ( CARPS ) . The CARPS contains a scanned screening measure and scoring algorithms and automatically produces patient and physician reports and patient education . RESULTS At baseline , 21 % were harmful drinkers , and 26 % were hazardous drinkers . The patient report and combined report interventions were each associated with greater odds of lower-risk drinking at follow-up than usual care ( odds ratio=1.59 and 1.23 , respectively , P<.05 for each ) . The patient report intervention significantly reduced harmful drinking at follow-up from an expected 21 % in usual care to 16 % and increased nonhazardous drinking from 52 % expected in usual care to 58 % . Patients in the combined report intervention experienced a significantly greater average decrease in quantity and frequency . CONCLUSION Older primary care patients can effectively reduce their alcohol consumption and other drinking risks when given personalized information about their drinking and health OBJECTIVES Among elderly patients , mental and physical illness are often present along with alcohol dependence . The interaction between alcohol use and concurrent physical or mental disabilities is complex and complicates treatment planning . The aim of this study was to test the efficacy of naltrexone combined with sertraline for the treatment of older adults with major depression and alcohol dependence . METHODS The sample was 74 subjects , age 55 and older , who met criteria for a depressive disorder along with alcohol dependence . All subjects were r and omly assigned to 12 weeks of naltrexone 50 mg/day or placebo . Also , all subjects received sertraline 100 mg/day and individual weekly psychosocial support . Treatment response for alcohol consumption and depression was measured during the 12 weeks of treatment . RESULTS At baseline , the average age of subjects was 63.4 , and subjects were drinking an average of 10.7 drinks per drinking day . The overall results are encouraging ; 42 % of the subjects had a remission of their depression and had no drinking relapses during the trial . There was no evidence for an added benefit of naltrexone in combination with sertraline , but there was significant correlation between any alcohol relapse during the trial and poor response to depression treatment . CONCLUSION Patients with concurrent mental disorders , such as major depression and alcohol dependence , are increasingly prevalent in clinical practice and have been demonstrated to show poorer treatment response and higher treatment costs . The results of this trial underscore the importance of addressing alcohol use in the context of treating late-life depression That structural characteristics act as markers of modified treatment outcome is a long st and ing idea in the alcohol treatment field . In order to test whether patient age is a factor to be considered in making treatment assignments , we examined data collected under a clinical trial . Two hundred and twenty-nine patients were r and omly assigned to one of three treatment conditions : extended cognitive behavioral treatment ( CB ) , relationship enhancement ( RE ) , or relationship and vocational enhancement ( VE ) . This paper reports on outcome ( alcohol use ) 3 - 6 months after treatment assignment . Our question was , would different age groups assigned to the treatment conditions exhibit different outcomes ? There were no significant main effects by either treatment condition or age group . There was a significant treatment condition by age group interaction . With increasing age , the differences in treatment seemed to increase . For the younger aged group ( 18 - 29 years old ) no statistically significant treatment differences were detected . Middle aged patients ( 30 - 49 years old ) did best in the RE condition . Older aged patients ( 50 + years old ) did best when assigned to the CB condition . These findings lead us to conclude that patient age is a variable which should be considered when testing patient-treatment matching hypotheses |
10,372 | 25,207,448 | The review concluded that programs working collaboratively or achieving shared leadership with a community can lead to behavior change and cost-effective sustained transformation to improve critical health behaviors and reduce poor health outcomes in low- and middle-income countries .
Overall , community engagement is an understudied component of improving child outcomes | As part of a broader evidence summit , USAID and UNICEF convened a literature review of effective means to empower communities to achieve behavioral and social changes to accelerate reductions in under-5 mortality and optimize early child development .
The authors conducted a systematic review of the effectiveness of community mobilization and participation that led to behavioral change and one or more of the following : child health , survival , and development . | Background Around a quarter of the world 's neonatal and maternal deaths occur in India . Morbidity and mortality are highest in rural areas and among the poorest wealth quintiles . Few interventions to improve maternal and newborn health outcomes with government-m and ated community health workers have been rigorously evaluated at scale in this setting .The study aims to assess the impact of a community mobilisation intervention with women 's groups facilitated by ASHAs to improve maternal and newborn health outcomes among rural tribal communities of Jharkh and and Orissa . Methods / design The study is a cluster-r and omised controlled trial and will be implemented in five districts , three in Jharkh and and two in Orissa . The unit of r and omisation is a rural cluster of approximately 5000 population . We identified villages within rural , tribal areas of five districts , approached them for participation in the study and enrolled them into 30 clusters , with approximately 10 ASHAs per cluster . Within each district , 6 clusters were r and omly allocated to receive the community intervention or to the control group , result ing in 15 intervention and 15 control clusters . R and omisation was carried out in the presence of local stakeholders who selected the cluster numbers and allocated them to intervention or control using a pre-generated r and om number sequence . The intervention is a participatory learning and action cycle where ASHAs support community women 's groups through a four-phase process in which they identify and prioritise local maternal and newborn health problems , implement strategies to address these and evaluate the result . The cycle is design ed to fit with the ASHAs ' m and ate to mobilise communities for health and to complement their other tasks , including increasing institutional delivery rates and providing home visits to mothers and newborns . The trial 's primary endpoint is neonatal mortality during 24 months of intervention . Additional endpoints include home care practice s and health care-seeking in the antenatal , delivery and postnatal period . The impact of the intervention will be measured through a prospect i ve surveillance system implemented by the project team , through which mothers will be interviewed around six weeks after delivery . Cost data and qualitative data are collected for cost-effectiveness and process evaluations . Study registration IS RCT N : IS RCT Background Maternal , perinatal and neonatal mortality remains high in low-income countries . We evaluated community and facility-based interventions to reduce deaths in three districts of Malawi . Methods We evaluated a rural participatory women ’s group community intervention ( CI ) and a quality improvement intervention at health centres ( FI ) via a two-by-two factorial cluster r and omized controlled trial . Consenting pregnant women were followed-up to 2 months after birth using key informants . Primary outcomes were maternal , perinatal and neonatal mortality . Clusters were health centre catchment areas assigned using stratified computer-generated r and omization . Following exclusions , including non-birthing facilities , 61 clusters were analysed : control ( 17 clusters , 4912 births ) , FI ( 15 , 5335 ) , CI ( 15 , 5080 ) and FI + CI ( 14 , 5249 ) . This trial was registered as International St and ard R and omised Controlled Trial [ IS RCT N18073903 ] . Outcomes for 14 576 and 20 576 births were recorded during baseline ( June 2007–September 2008 ) and intervention ( October 2008–December 2010 ) periods . Results For control , FI , CI and FI + CI clusters neonatal mortality rates were 34.0 , 28.3 , 29.9 and 27.0 neonatal deaths per 1000 live births and perinatal mortality rates were 56.2 , 55.1 , 48.0 and 48.4 per 1000 births , during the intervention period . Adjusting for clustering and stratification , the neonatal mortality rate was 22 % lower in FI + CI than control clusters ( OR = 0.78 , 95 % CI 0.60–1.01 ) , and the perinatal mortality rate was 16 % lower in CI clusters ( OR = 0.84 , 95 % CI 0.72–0.97 ) . We did not observe any intervention effects on maternal mortality . Conclusions Despite implementation problems , a combined community and facility approach using participatory women ’s groups and quality improvement at health centres reduced newborn mortality in rural Malawi BACKGROUND Women 's groups and health education by peer counsellors can improve the health of mothers and children . We assessed their effects on mortality and breastfeeding rates in rural Malawi . METHODS We did a 2 × 2 factorial , cluster-r and omised trial in 185,888 people in Mchinji district . 48 equal-sized clusters were r and omly allocated to four groups with a computer-generated number sequence . 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems . 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care . Primary outcomes for the women 's group intervention were maternal , perinatal , neonatal , and infant mortality rates ( MMR , PMR , NMR , and IMR , respectively ) ; and for the peer counselling were IMR and exclusive breastfeeding ( EBF ) rates . Analysis was by intention to treat . The trial is registered as IS RCT N06477126 . FINDINGS We monitored outcomes of 26,262 births between 2005 and 2009 . In a factorial model adjusted only for clustering and the volunteer peer counselling intervention , in women 's group areas , for years 2 and 3 , we noted non-significant decreases in NMR ( odds ratio 0.93 , 0.64 - 1.35 ) and MMR ( 0.54 , 0.28 - 1.04 ) . After adjustment for parity , socioeconomic quintile , and baseline measures , effects were larger for NMR ( 0.85 , 0.59 - 1.22 ) and MMR ( 0.48 , 0.26 - 0.91 ) . Because of the interaction between the two interventions , a stratified analysis was done . For women 's groups , in adjusted analyses , MMR fell by 74 % ( 0.26 , 0.10 - 0.70 ) , and NMR by 41 % ( 0.59 , 0.40 - 0.86 ) in areas with no peer counsellors , but there was no effect in areas with counsellors ( 1.09 , 0.40 - 2.98 , and 1.38 , 0.75 - 2.54 ) . Factorial analysis for the peer counselling intervention for years 1 - 3 showed a fall in IMR of 18 % ( 0.82 , 0.67 - 1.00 ) and an improvement in EBF rates ( 2.42 , 1.48 - 3.96 ) . The results of the stratified , adjusted analysis showed a 36 % reduction in IMR ( 0.64 , 0.48 - 0.85 ) but no effect on EBF ( 1.18 , 0.63 - 2.25 ) in areas without women 's groups , and in areas with women 's groups there was no effect on IMR ( 1.05 , 0.82 - 1.36 ) and an increase in EBF ( 5.02 , 2.67 - 9.44 ) . The cost of women 's groups was US$ 114 per year of life lost ( YLL ) averted and that of peer counsellors was $ 33 per YLL averted , using stratified data from single intervention comparisons . INTERPRETATION Community mobilisation through women 's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural population s in Africa . FUNDING Saving Newborn Lives , UK Department for International Development , and Wellcome Trust BACKGROUND Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years . 90 % of deliveries in the poorest quintile of households happen at home . We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates . METHODS We pair-matched 42 geopolitical clusters in Makwanpur district , Nepal , selected 12 pairs r and omly , and r and omly assigned one of each pair to intervention or control . In each intervention cluster ( average population 7000 ) , a female facilitator convened nine women 's group meetings every month . The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them . We monitored birth outcomes in a cohort of 28?931 women , of whom 8 % joined the groups . The primary outcome was neonatal mortality rate . Other outcomes included stillbirths and maternal deaths , uptake of antenatal and delivery services , home care practice s , infant morbidity , and health-care seeking . Analysis was by intention to treat . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N31137309 . FINDINGS From 2001 to 2003 , the neonatal mortality rate was 26.2 per 1000 ( 76 deaths per 2899 livebirths ) in intervention clusters compared with 36.9 per 1000 ( 119 deaths per 3226 livebirths ) in controls ( adjusted odds ratio 0.70 [ 95 % CI 0.53 - 0.94 ] ) . Stillbirth rates were similar in both groups . The maternal mortality ratio was 69 per 100000 ( two deaths per 2899 livebirths ) in intervention clusters compared with 341 per 100000 ( 11 deaths per 3226 livebirths ) in control clusters ( 0.22 [ 0.05 - 0.90 ] ) . Women in intervention clusters were more likely to have antenatal care , institutional delivery , trained birth attendance , and hygienic care than were controls . INTERPRETATION Birth outcomes in a poor rural population improved greatly through a low cost , potentially sustainable and scalable , participatory intervention with women 's groups Background Progress on neonatal survival has been slow in most countries . While there is evidence on what works to reduce newborn mortality , there is limited knowledge on how to deliver interventions effectively when health systems are weak . Cluster r and omized trials have shown strong reductions in neonatal mortality using community mobilisation with women 's groups in rural Nepal and India . A similar trial in Bangladesh showed no impact . A main hypothesis is that this negative finding is due to the much lower coverage of women 's groups in the intervention population in Bangladesh compared to India and Nepal . For evidence -based policy making it is important to examine if women 's group coverage is a main determinant of their impact . The study aims to test the effect on newborn and maternal health outcomes of a participatory women 's group intervention with a high population coverage of women 's groups . Methods A cluster r and omised trial of a participatory women 's group intervention will be conducted in 3 districts of rural Bangladesh . As we aim to study a women 's group intervention with high population coverage , the same 9 intervention and 9 control unions will be used as in the 2005 - 2007 trial . These had been r and omly allocated using the districts as strata . To increase coverage , 648 new groups were formed in addition to the 162 existing groups that were part of the previous trial . An open cohort of women who are permanent residents in the union in which their delivery or death was identified , is enrolled . Women and their newborns are included after birth , or , if a woman dies during pregnancy , after her death . Excluded are women who are temporary residents in the union in which their birth or death was identified . The primary outcome is neonatal mortality in the last 24 months of the study . A low cost surveillance system will be used to record all birth outcomes and deaths to women of reproductive age in the study population . Data on home care practice s and health care use are collected through interviews . Trial registration IS RCT N : IS RCT Increased interest in the potential contribution of insecticide-impregnated bed nets ( ITBN ) to malaria control has led to research efforts to determine the impact and sustainability of ITBN programmes in differing environments . There is a need to develop effective , feasible educational strategies that will both inform and motivate community members , and thus maximize the correct usage of ITBN . This is especially true in communities where indigenous usage of bed nets is low . This paper describes the educational component of a r and omized controlled community intervention trial of ITBN , with childhood malaria morbidity as an outcome . The educational approach and messages for the ITBN trial were developed from anthropological survey data collected 4 years before the trial , and from community surveys conducted by project research ers . Low levels of underst and ing amongst mothers of the aetiological link between mosquitos and malaria led to the exclusion of the term ' malaria ' from the initial educational messages promoting the use of ITBN . Appropriate individuals within the existing district health care structure were trained as community educators in the project . These educators conducted intensive teaching in the community through public meetings and group teaching in the first 6 months of the trial . The impact of these initial activities was assessed through interviews with a r and om sample of 100 mothers and 50 household heads . This allowed the identification of messages which had not been well understood and further educational methods were chosen to address the areas pinpointed . The community assessment also demonstrated that , in 1994 , over 90 % of mothers understood a protective role for bed nets against malaria and the ITBN education messages were changed to take account of this . The school programme was evaluated through determining outreach ( the number of households accessed ) , changes in participant children 's knowledge , post-teaching assessment of mothers ' knowledge and discussion s with parent-teacher associations . It was shown that 40 % of intervention homes with children in the target group were accessed , participant children learned the educational messages well ( scores increased from a pre-teaching mean of 59 % to a post-teaching mean of 92 % ) and a high level of awareness of the ITBN trial was achieved in these homes ( 75 % ) . However , specific messages of the education programmed were not well transferred to the home ( 30 % ) . The discussion emphasises the need for allocation of adequate re sources for education in programmes dependent on achieving a change in community practice s. We also describe the value of ongoing communication between programme planners and a target population in maximizing the effectiveness of messages and methods used 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 Background Few large and rigorous evaluations of participatory interventions systematic ally describe their context and implementation , or attempt to explain the mechanisms behind their impact . This study reports process evaluation data from the Ekjut cluster-r and omised controlled trial of a participatory learning and action cycle with women 's groups to improve maternal and newborn health outcomes in Jharkh and and Orissa , eastern India ( 2005 - 2008 ) . The study demonstrated a 45 % reduction in neonatal mortality in the last two years of the intervention , largely driven by improvements in safe practice s for home deliveries . Methods A participatory learning and action cycle with 244 women 's groups was implemented in 18 intervention clusters covering an estimated population of 114 141 . We describe the context , content , and implementation of this intervention , identify potential mechanisms behind its impact , and report challenges experienced in the field . Methods included a review of intervention documents , qualitative structured discussion s with group members and non-group members , meeting observations , as well as descriptive statistical analysis of data on meeting attendance , activities , and characteristics of group attendees . Results Six broad , interrelated factors influenced the intervention 's impact : ( 1 ) acceptability ; ( 2 ) a participatory approach to the development of knowledge , skills and ' critical consciousness ' ; ( 3 ) community involvement beyond the groups ; ( 4 ) a focus on marginalized communities ; ( 5 ) the active recruitment of newly pregnant women into groups ; ( 6 ) high population coverage . We hypothesize that these factors were responsible for the increase in safe delivery and care practice s that led to the reduction in neonatal mortality demonstrated in the Ekjut trial . Conclusions Participatory interventions with community groups can influence maternal and child health outcomes if key intervention characteristics are preserved and tailored to local context s. Scaling-up such interventions requires ( 1 ) a detailed underst and ing of the way in which context affects the acceptability and delivery of the intervention ; ( 2 ) planned but flexible replication of key content and implementation features ; ( 3 ) strong support for participatory methods from implementing agencies BACKGROUND In rural India , most births take place in the home , where high-risk care practice s are common . We developed an intervention of behaviour change management , with a focus on prevention of hypothermia , aim ed at modifying practice s and reducing neonatal mortality . METHODS We did a cluster-r and omised controlled efficacy trial in Shivgarh , a rural area in Uttar Pradesh . 39 village administrative units ( population 104,123 ) were allocated to one of three groups : a control group , which received the usual services of governmental and non-governmental organisations in the area ; an intervention group , which received a preventive package of interventions for essential newborn care ( birth preparedness , clean delivery and cord care , thermal care [ including skin-to-skin care ] , breastfeeding promotion , and danger sign recognition ) ; or another intervention group , which received the package of essential newborn care plus use of a liquid crystal hypothermia indicator ( ThermoSpot ) . In the intervention clusters , community health workers delivered the packages via collective meetings and two antenatal and two postnatal household visitations . Outcome measures included changes in newborn-care practice s and neonatal mortality rate compared with the control group . Analysis was by intention to treat . This study is registered as International St and ard R and omised Control Trial , number NCT00198653 . FINDINGS Improvements in birth preparedness , hygienic delivery , thermal care ( including skin-to-skin care ) , umbilical cord care , skin care , and breastfeeding were seen in intervention arms . There was little change in care-seeking . Compared with controls , neonatal mortality rate was reduced by 54 % in the essential newborn-care intervention ( rate ratio 0.46 [ 95 % CI 0.35 - 0.60 ] , p<0.0001 ) and by 52 % in the essential newborn care plus ThermoSpot arm ( 0.48 [ 95 % CI 0.35 - 0.66 ] , p<0.0001 ) . INTERPRETATION A socioculturally context ualised , community-based intervention , targeted at high-risk newborn-care practice s , can lead to substantial behavioural modification and reduction in neonatal mortality . This approach can be applied to behaviour change along the continuum of care , harmonise vertical interventions , and build community capacity for sustained development . FUNDING USAID and Save the Children-US through a grant from the Bill & Melinda Gates Foundation Introduction The main challenge for achieving universal health coverage in India is ensuring effective coverage of poor and vulnerable communities in the face of high levels of income and gender inequity in access to health care . Drawing on the social capital generated through women ’s participation in community organizations like SHGs can influence health outcomes . To date , evidence about the impact of SHGs on health outcomes has been derived from pilot-level interventions , some using r and omised controlled trials and other rigorous methods . While the evidence from these studies is convincing , our study is the first to analyse the impact of SHGs at national level . Methods We analyzed the entire data set from the third national District Level Household Survey from 601 districts in India to assess the impact of the presence of SHGs on maternal health service uptake . The primary predictor variable was presence of a SHG in the village . The outcome variables were : institutional delivery ; feeding new-borns colostrum ; knowledge about family planning methods ; and ever used family planning . We controlled for respondent education , wealth , heard or seen health messages , availability of health facilities and the existence of a village health and sanitation committee . Results Stepwise logistic regression shows respondents from villages with a SHG were 19 per cent ( OR : 1.19 , CI : 1.13 - 1.24 ) more likely to have delivered in an institution , 8 per cent ( OR : 1.08 , CI : 1.05 - 1.14 ) more likely to have fed newborns colostrum , have knowledge ( OR : 1.48 , CI 1.39 – 1.57 ) and utilized ( OR : 1.19 , CI 1.11 – 1.27 ) family planning products and services . These results are significant after controlling for individual and village-level heterogeneities and are consistent with existing literature that the social capital generated through women ’s participation in SHGs influences health outcome . Conclusion The study concludes that the presence of SHGs in a village is associated with higher knowledge of family planning and maternal health service uptake in rural India . To achieve the goal of improving public health nationally , there is a need to underst and more fully the benefits of systematic collaboration between the public health community and these grassroots organizations OBJECTIVE To determine whether a women 's group intervention involving participatory learning and action has a sustainable and replicable effect on neonatal survival in rural , eastern India . METHODS From 2004 to 2011 , births and neonatal deaths in 36 geographical clusters in Jharkh and and Odisha were monitored . Between 2005 and 2008 , these clusters were part of a r and omized controlled trial of how women 's group meetings involving participatory learning and action influence maternal and neonatal health . Between 2008 and 2011 , groups in the original intervention clusters ( zone 1 ) continued to meet to discuss post-neonatal issues and new groups in the original control clusters ( zone 2 ) met to discuss neonatal health . Logistic regression was used to examine neonatal mortality rates after 2008 in the two zones . FINDINGS Data on 41,191 births were analysed . In zone 1 , the intervention 's effect was sustained : the cluster-mean neonatal mortality rate was 34.2 per 1000 live births ( 95 % confidence interval , CI : 28.3 - 40.0 ) between 2008 and 2011 , compared with 41.3 per 1000 live births ( 95 % CI : 35.4 - 47.1 ) between 2005 and 2008 . The effect of the intervention was replicated in zone 2 : the cluster-mean neonatal mortality rate decreased from 61.8 to 40.5 per 1000 live births between two periods : 2006 - 2008 and 2009 - 2011 ( odds ratio : 0.69 , 95 % CI : 0.57 - 0.83 ) . Hygiene during delivery , thermal care of the neonate and exclusive breastfeeding were important factors . CONCLUSION The effect of participatory women 's groups on neonatal survival in rural India , where neonatal mortality is high , was sustainable and replicable IMPORTANCE Community-based interventions can reduce neonatal mortality when health systems are weak . Population coverage of target groups may be an important determinant of their effect on behavior and mortality . A women 's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality , despite a similar intervention having a significant effect on neonatal and maternal death in comparable setting s. OBJECTIVE To assess the effect of a participatory women 's group intervention with higher population coverage on neonatal mortality in Bangladesh . DESIGN A cluster r and omized controlled trial in 9 intervention and 9 control clusters . SETTING Rural Bangladesh . PARTICIPANTS Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention . INTERVENTIONS Women 's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues . MAIN OUTCOMES AND MEASURES Neonatal mortality rate . RESULTS Analysis included 19 301 births during the final 24 months of the intervention . More than one-third of newly pregnant women joined the groups . The neonatal mortality rate was significantly lower in the intervention arm ( 21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas ) , a reduction in neonatal mortality of 38 % ( risk ratio , 0.62 [ 95 % CI , 0.43 - 0.89 ] ) when adjusted for socioeconomic factors . The cost-effectiveness was US $ 220 to $ 393 per year of life lost averted . Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight . Improvements were seen in hygienic home delivery practice s , newborn thermal care , and breastfeeding practice s. CONCLUSIONS AND RELEVANCE Women 's group community mobilization , delivered at adequate population coverage , is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N01805825 Lars Åke Persson and colleagues conduct a cluster r and omised control in northern Vietnam to analyze the effect of the activity of local community-based maternal- and -newborn stakeholder groups on neonatal mortality . Please see later in the article for the Editors ' BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N21817853 . FINDINGS After baseline surveillance of 4692 births , we monitored outcomes for 19 030 births during 3 years ( 2005 - 08 ) . NMRs per 1000 were 55.6 , 37.1 , and 36.3 during the first , second , and third years , respectively , in intervention clusters , and 53.4 , 59.6 , and 64.3 , respectively , in control clusters . NMR was 32 % lower in intervention clusters adjusted for clustering , stratification , and baseline differences ( odds ratio 0.68 , 95 % CI 0.59 - 0.78 ) during the 3 years , and 45 % lower in years 2 and 3 ( 0.55 , 0.46 - 0.66 ) . Although we did not note a significant effect on maternal depression overall , reduction in moderate depression was 57 % in year 3 ( 0.43 , 0.23 - 0.80 ) . INTERPRETATION This intervention could be used with or as a potential alternative to health-worker-led interventions , and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor population s. FUNDING Health Foundation , UK Department for International Development , Wellcome Trust , and the Big Lottery Fund ( UK ) Save the Children 's ( SC ) successful integrated nutrition program in Viet Nam , the poverty alleviation and nutrition program ( PANP ) , uses the positive deviance ( PD ) approach to identify key growth promoting behaviors and provides participatory adult education allowing mothers to develop skills related to these behaviors . We investigated whether improvements seen during a PANP intervention ( 1993–1995 ) were sustained three and four years after SC 's departure . Cross-sectional surveys were administered to 46 r and omly selected households in four communes that had previously participated in the PANP and 25 households in a neighboring comparison community in 1998 and 1999 . Two children per household , an older child who had participated in the PANP and a younger sibling who had not , were measured ( total n = 142 children ) , and their mothers were interviewed . Older SC children tended to be better nourished than their counterparts . Their younger siblings were significantly better nourished than those in the comparison group , with adjusted mean weight-for-age Z scores of −1.82 versus −2.45 ( p = .007 ) , weight-for-height Z scores of −0.71 versus −1.45 ( p < .001 ) , and height-for-age Z scores of −2.11 and −2.37 ( ns , p = .4 ) , respectively . SC mothers reporting feeding the younger siblings more than their counterparts did ( 2.9 versus 2.2 main meals per day , p < .001 , and 96.2 % versus 52 % offering snacks , p < .01 ] . SC mothers reported washing their h and s “ often ” more than comparison mothers ( 100 % vs. 76 % , p < .001 ) . Growth-promoting behaviors identified through PD studies and practice d through neighborhood-based rehabilitation sessions persisted years after program completion . These sustained behaviors contributed to better growth of younger siblings never exposed to the program The persistence of high perinatal and neonatal mortality rates in many developing countries make efforts to improve perinatal care in the home and at local health facilities important public health concerns . We describe a study which aims to evaluate a community-level participatory intervention in rural Nepal . The effectiveness of community-based action research interventions with mothers and other key members of the community in improving perinatal health outcomes is being examined using a cluster r and omized , controlled trial covering a population of 28,000 married women of reproductive age . The unit of r and omization was the village development committee ( VDC ) : 12 VDCs receive the intervention while 12 serve as controls . The key elements of the intervention are the activities of female facilitators , each of whom works in one VDC facilitating the activities of women 's groups in addressing problems in pregnancy , childbirth and the newborn period . Each group moves through a participatory planning cycle of assessment , sharing experiences , planning , action and re assessment , with the aim of improving essential maternal and newborn care . Outcomes assessed are neonatal and perinatal mortality rates , changes in patterns of home care , health care seeking and referral . The study also aims to generate programmatic information on the process of implementation in communities This three-phase study characterized , vali date d , and applied community capacity domains in a health communication project evaluation in Zambia . Phase I explored community capacity domains from community members ' perspectives ( 16 focus groups , 14 in-depth interviews , 4 sites . These were vali date d in Phase II with 720 r and omly selected adults . The vali date d domains were incorporated into a program evaluation survey ( 2,462 adult women , 2,354 adult men ; October 2009 ) . The results indicated that the intervention had direct effects on community capacity ; enhanced capacity was then associated with having taken community action for health . Finally , community capacity mediated by community action and controlling for confounders , had a significant effect on women 's contraceptive use , children 's bed net use , and HIV testing . The results indicate that building community capacity served as a means to an end — improved health behaviors and reported collective action for health— and an end-in-itself , both of which are essential to overall wellbeing A community-based intervention was developed through direct participation of the target population in assessment and iterative trials to improve hygiene practice s and to reduce childhood diarrhoea in lowl and rural Bangladesh . A total of 185 ( 98 % ) households with children ages 0 - 18 months in five contiguous villages were targeted for the interventions . A comparison site was selected for a detailed observational study and for use as a control for the intervention . About 97 % of all households with children ages 0 - 18 months were enrolled for study at the control site . Children in this age group were targeted because at this developmental stage they were most vulnerable to diarrhoeal morbidity and malnutrition ( related to unhygienic practice s ) . The intervention was implemented with the assistance of village leaders through a " Clean Life " campaign by local project workers and volunteer mothers who were chosen from the target households . The intervention activities started in January 1986 and lasted for 7 months . Higher adoption rates of the intervention were associated with better cleanliness status , which was related to lower diarrhoea and malnutrition rates in the intervention site . The results of between-site longitudinal analyses showed that after the intervention , the intervention site had substantially higher cleanliness scores , lower diarrhoeal morbidity , and better growth status compared to those of the control site , with differences increasing over time . The findings suggest that this type of community-based intervention can be very beneficial in modifying hygiene behaviours and lowering childhood diarrhoea and malnutrition OBJECTIVE To assess whether the development and implementation of a community health worker ( CHW ) project in rural Kenya was associated with an increase in knowledge about malaria and the use of insecticide-treated nets ( ITNs ) in children under five years of age . METHODS A baseline knowledge and behavior question naire , adopted from the Kenyan Demographic Health Survey , was conducted in August 2007 by Kenyan health officials in 75 villages . Two CHWs were chosen from each village and trained in appropriate use of ITNs . The CHWs provided educational sessions and ITNs to mothers in their respective villages . A follow-up survey was conducted in March 2008 of all families with children less than five years of age within r and omly selected villages . The main questions addressed during the follow-up survey included knowledge about malaria and the practice of correctly using ITNs . FINDINGS There were 267 surveys compiled for knowledge assessment before the intervention and 340 in the post-intervention analysis with an approximate 99 % family participation rate . Of the families surveyed , 81 % correctly knew the cause for malaria before the study and 93 % after the CHW intervention ( p < 0.01 ) . Of those surveyed before the intervention , 70 % owned and correctly used mosquito nets compared with 88 % after the CHW intervention ( p < 0.01 ) . CONCLUSIONS There was a significant increase in knowledge about malaria and use of ITNs after the implementation of the CHW program OBJECTIVE To assess the effect on maternal health outcomes of a community-based behavior change management intervention for essential newborn care leading to a reduction in neonatal mortality . METHODS A cluster-r and omized controlled trial involving 1 control and 2 intervention arms was conducted in Shivgarh , India , between January 2004 and May 2005 . Risk-enhancing domiciliary newborn care behaviors , including those posing a concomitant risk to maternal health , were targeted through home visits and community meetings . Secondary outcomes included knowledge of maternal danger signs , self-reported complications , maternal care practice s , care-seeking from trained providers , and maternal mortality ratio ( MMR ) . The intervention arms were combined for analysis , which was done by intention to treat . RESULTS Significant improvements were observed in maternal health equity and outcomes including knowledge of danger signs , care practice s , self-reported complications , and timely care-seeking from trained providers . The difference in adjusted MMR was not significant ( relative risk 0.44 ; 95 % confidence interval , 0.14 - 1.43 ; P=0.11 ) owing to the inadequate sample size for this outcome , but may suggest a decline in MMR given improvements in other outcomes in the causal pathway to mortality . CONCLUSION Community-based strategies focused on prevention and care-seeking effectively complemented facility-based strategies toward improving maternal health , while synergizing with newborn care interventions Malaria remains a vital concern of child survival in sub-Saharan Africa despite the existence of effective curative and preventive measures . It is known that child malaria is underpinned by factors such as socioeconomic , cultural , environmental , and so forth , that must be considered simultaneously in order to effectively control it . This study applied to a rural community in Benin ( West Africa ) the Health Promotion concept ( community participation and empowerment , context ualism , intersectorality , multi strategy , equity , and sustainability ) to develop a program in order to control child malaria and close the gap of unsuccessful programs . The study design was a quasi-experimental pre-post conducted over a period of 27 months . As results , 80 % of the community members participated in six of the seven sub-projects planned . The prevalence of fever ( malaria ) was significantly reduced after the intervention ( p = 0.008 ) . The recourse to adequate health care has significantly increased after the intervention ( χ2 = 48.07 , p = 0.000000 ) . All these contributed to a statistically significant reduction of children deaths due to malaria ( p = 0.001 ) in the village . Health Promotion strategies are likely to contribute to sustainable malaria programs ' implementation that reduce malaria incidence and deaths in children under five OBJECTIVE Unintentional injury rates in low- and middle-income countries are up to 50 times higher than high-income nations . In South Africa , kerosene ( paraffin ) is a leading cause of poisoning and burns , particularly in low-income communities where it serves as a primary fuel for light , cooking , and heating . This study tested a community-based intervention to reduce kerosene-related injury risk . The intervention used a train-the-trainers model , whereby expert trainers train local paraprofessionals , who in turn deliver educational material s to community residents . The intervention was theory-driven , pragmatically motivated , and culturally sensitive . DESIGN Prospect i ve quasi-experimental intervention design with nonequivalent case versus control groups . MAIN OUTCOME MEASURES Three primary outcome measures were considered : self-reported knowledge of kerosene safety , observed practice of safe kerosene use , and self-reported recognition of risk for kerosene-related injury . RESULTS ANOVA models suggest a large and significant increase in self-reported kerosene-related knowledge in the intervention community compared to the control community . There were smaller , but statistically significant changes , in kerosene-related safety practice s and recognition of kerosene injury risk in the intervention community compared to the control community . CONCLUSION The intervention was successful . A train-the-trainers model might be an effective educational tool to reduce kerosene-related injury risk in low-income communities within low- and middle-income countries This article review s the implementation of the community component of the Integrated Management of Childhood Illness ( IMCI ) strategy in Chao , Peru ( 2001 to 2004 ) and San Luis , Honduras ( 2003 to 2005 ) . An evaluation was conducted in 2005 and included a project documentation review , key-informant interviews , and a household level baseline and follow-up survey of the WHO/UNICEF key family practice s in each intervention site . The promotion of the key family practice s in Chao and San Luís demonstrated measurable success . In comparison with the initial survey in 2002 , the percentage of participant mothers ( N = 78 ) in Chao in 2004 who knew that they should breastfeed exclusively for at least six months increased from 33 % to 94 % ; the presentation of complete vaccination records for one-year-old children increased by 19 % ; the recognition of danger signs for pneumonia increased 18 % and for diarrhea by 8 % ; and the percentage of mothers who received four or more prenatal check-ups increased by 25 % . A dramatic reduction in malaria cases was also attributed to the intervention in Chao . In San Luis , a quasi-experimental , r and om household sample ( N = 300 ) showed that the incidence of diarrheal disease among children under five years old declined by 18 % between survey rounds ( from 44 % in August 2004 to 26 % in December 2005 ) . Social mobilization has promoted inter-sector consensus-building around community health issues , especially those related to maternal and child health . The promotion of the participation of representatives from various organizations via the community IMCI social-actor methodology has led to increased civic cooperation . Positive changes in health behaviors have been documented through an increase in preventive health practice s , greater dem and for primary health care services , and concrete community actions to improve public health . ( Promot Educ 2008;15(2 ) : 15—20 |
10,373 | 28,697,200 | Implant-supported prostheses were more cost-effective when compared to conventional dentures and fixed implant-supported prostheses .
Overdentures supported by two implants and magnet attachment were reported as cost-effective .
CONCLUSION Implant-supported overdentures are a cost-effective treatment for edentulous patients . | PURPOSE Edentulous patients benefit significantly from implant-supported overdenture prostheses .
The purpose of this systematic review was to evaluate the cost-effectiveness of implant-supported overdentures ( IODs ) for edentulous patients . | PURPOSE This r and omized clinical trial tested hypotheses that there are no differences in patient satisfaction , component costs , or treatment and maintenance times when m and ibular overdentures are retained by one or two implants . MATERIAL S AND METHODS Subjects wearing conventional complete dentures were r and omized to receive either one midline or two bilateral m and ibular implants followed by a m and ibular denture reline to incorporate implant retention . They indicated on a visual analog scale satisfaction with their dentures before implants and at 2 months and 1 year after implant retention . Satisfaction outcomes between the two groups were compared using the Wilcoxon/Mann-Whitney nonparametric rank test , while changes within each group were analyzed using signed-rank tests . Component costs and times for surgery , prosthodontic treatment , and maintenance were compared using nonparametric and t tests . RESULTS Eighty-six subjects enrolled in this study and 85 completed the 1-year follow-up , at which median satisfaction was 93 ( maximum 100 ) in the single-implant group and 94 in the two-implant group ( P > .5 ) . Within each group , median improvement in satisfaction was similarly dramatic ( approximately 44 ) and significant ( P < .001 ) . Prosthodontic maintenance time was similar for both groups ( P > .37 ) , but the single-implant group had significantly lower component costs ( P < .001 ) and lower times for surgery ( P = .002 ) , postsurgical denture maintenance ( P = .021 ) , and denture reline ( P < .001 ) . Five implants failed in four subjects , all in the two-implant group and all before denture reline . CONCLUSION Lower component costs and treatment times , with comparable satisfaction and maintenance time over the first year , indicate that a m and ibular overdenture retained by a single midline implant may be an alternative to the customary two-implant overdenture for maladaptive denture patients The effectiveness of dental implants is widely studied , especially in terms of their clinical outcomes . However , from the policymaker 's point of view , variables other than safety and efficacy , such as the costs and effectiveness of dental implants as compared to other treatment alternatives , are vital in decision making . This paper compares the costs of different treatment strategies in a r and omized clinical trial in patients with resorbed m and ibles and persistent problems with their conventional dentures : treatment with a m and ibular overdenture on permucosal dental implants , an overdenture on a transm and ibular implant , new dentures after preprosthetic surgery , and new dentures only . Data were gathered on an individual patient level to gain insight into specific cost episodes . Direct costs were subdivided into labor , material , technique , and overhead . Data concerning these components were gathered during the consecutive treatment phases in the first year . Results show that the re sources used to treat a patient with an overdenture supported by a transm and ibular implant are seven times those of a complete new set of dentures . Comparison of the cost ratio of an implant-retained overdenture supported by permucosal implants and conventional new prostheses proves less unfavorable : 1:3 . New dentures after preprosthetic surgery are almost as expensive as treatment with permucosal implants PURPOSE The purpose of this study was to compare elderly patients ' satisfaction and oral health-related quality of life with m and ibular two-implant overdentures and conventional dentures . MATERIAL S AND METHODS Sixty edentulous subjects aged 65 to 75 years were r and omly assigned to two groups treated with maxillary conventional dentures and either a m and ibular conventional denture ( n = 30 ) or an overdenture supported by two implants with ball retainers ( n = 30 ) . Subjects rated their general satisfaction , as well as other features of their dentures ( comfort , stability , ability to chew , speech , esthetics , and cleaning ability ) , prior to treatment and 2 months postdelivery . Changes in ratings on the original Oral Health Impact Profile ( OHIP ) and its short form ( OHIP-EDENT ) were also used as indicators of oral health-related quality of life . RESULTS The primary outcome of this study , ratings of general satisfaction 2 months postdelivery , was significantly better in the group treated with m and ibular two-implant overdentures ( P = .001 ) . In addition , the implant group gave significantly higher ratings on comfort , stability , and ability to chew . Furthermore , using OHIP-EDENT , subjects who received m and ibular two-implant overdentures had significantly fewer oral health-related quality of life problems than did the conventional group . CONCLUSION These short-term results suggest that m and ibular two-implant overdentures combined with maxillary conventional dentures provide better function and oral health-related quality of life than conventional dentures Implementation of new therapies is usually governed by financial considerations , so efficacy studies should also include cost comparisons . The cost and effectiveness of m and ibular conventional dentures ( CD , n = 30 ) and two-implant overdentures ( IOD , n = 30 ) were compared in elderly subjects . Effectiveness ( Oral Health Impact Profile , OHIP-20 ) and cost were measured up to one year post-treatment . Data for subsequent years were estimated by the Delphi method . Using an average life expectancy of 17.9 years , the equalized annual costs ( in Canadian dollars ) were $ 399 for CD and $ 625 for IOD ( p < 0.001 ) , and the equalized annual values for the outcome ( OHIP-20 ) were 47.0 for CD and 31.3 for IOD treatment ( p < 0.05 ) . These values translate into a yearly additional cost for IOD treatment of $ 14.41 per OHIP-20 point . These results are key to the implementation of programs to provide this form of therapy for edentulous adults UNLABELLED Implant overdentures and conventional prostheses have been compared in several trials using a variety of functional and oral health-related quality of life ( OHQOL ) outcomes . In this paper , we describe the impact of implant overdentures on general and OHQOL in seniors . OBJECTIVES To compare the oral health-related and general quality of life of seniors ( aged 65 - 75 years ) who received either m and ibular implant overdentures or conventional dentures . METHODS Sixty edentulous patients were recruited . Thirty received m and ibular overdentures retained by two implants ( IOD ) and a conventional maxillary denture , the other 30 subjects received new maxillary and m and ibular conventional complete dentures ( CD ) . All completed the 20-item version of the Oral Health Impact Profile ( OHIP-20 ) before treatment , then at two and 6 months after delivery of the dentures . The SF-36 general health question naire was completed at baseline and 6 months only . RESULTS Pretreatment and 6-month data from 55 subjects were analyzed . Those who received the IODs had significantly better OHIP-20 total scores at 6 months . Results for IOD subjects were also superior in the functional limitation , physical pain , physical disability and psychological disability subscales . While no significant between group difference was found on the SF-36 health survey , significant pre-post-treatment differences within the IOD group were detected for the role emotional , vitality and the social function scales . CONCLUSIONS M and ibular overdentures retained by two implants provide elderly patients with better OHQOL . General health-related quality of life improved in the implant group PURPOSE This study aim ed to compare the prosthetic aspects and patient satisfaction with prosthetic care in two-implant-retained m and ibular overdentures , whether implants were splinted with a bar or left with magnets or ball attachments . MATERIAL S AND METHODS Thirty-six completely edentulous patients had two Brånemark implants placed in the m and ibular canine area . A r and omized procedure allocated patients into three groups of equal size , each with a different attachment system : bars , magnets , or balls . Prosthesis retention and mechanical as well as soft tissue complications were recorded in addition to patient satisfaction . A linear mixed model was fitted with attachment type and time as classification variables and adjusted by Turkey 's multiple range test . RESULTS Ball-retained overdentures showed at year 10 the greatest vertical retention force ( 1,327 g ) , followed by bars ( 1,067 g ) and magnets ( 219 g ) . In the ball group , need for tightening of abutment screws was the most common mechanical complication ; in the magnet and bar groups , respectively , the most common complications were wear and corrosion , and the need for clip activation . Prosthesis stability and chewing comfort for the overdenture were rated significantly lower for the magnet group compared to the ball and bar groups . Prosthesis stability of the maxillary denture was rated significantly lower in the bar group compared to ball and magnet groups . CONCLUSION The ball group scored best in relation to retention of the overdenture , soft tissue complications , and patient satisfaction at year 10 . The bar group scored lower for comfort and stability of the maxillary denture . Magnets offered patients the least comfort The importance of assessing the impact of treatments for chronic conditions on an individual 's quality of life has been well-established . In this r and omized clinical trial , oral-health-rclated quality of life , measured with the Oral Health Impact Profile ( OHIP ) , was compared between two groups of edentulous patients . One group ( n = 54 ) received m and ibular implant-supported overdentures , and the other group ( n = 48 ) received conventional dentures . Assessment s were performed pre-treatment and two months after the prostheses were delivered . The multivariate model showed that implant treatment was significantly associated with lower post-treatment OHIP scores ( p = 0.0002 ) , indicating a better quality of life . In addition , pre-treatment OHIP scores , treatment allocation , age , sex , and marital status explained 31 % of the variation in post-treatment OHIP scores ( F = 0.0001 ) . These results suggest that implant treatment provides significant short-term improvement over conventional treatment in oral-health-related quality of life Studies have shown that m and ibular implant overdentures significantly increase satisfaction and quality of life of edentulous elders . Improved chewing ability appears to have a positive impact on nutritional state . Therefore , it is important to determine the best design of this prosthesis over the long term . In this r and omized controlled trial , three groups of edentulous participants with atrophic m and ibles wore 3 types of implant overdentures . During an eight-year follow-up , only seven of the 110 participants had dropped out of this study . Almost all participants were still satisfied with their overdentures . Participant satisfaction concerning retention and stability of the m and ibular overdenture had decreased significantly in the two-implant ball attachment group , whereas the opinion of participants in the single- and triple-bar groups was still at the same level . The long-term results suggest that a m and ibular overdenture retained by 2 implants with a single bar may be the best treatment strategy for edentulous people with atrophic ridges PURPOSE This work compared implant-supported fixed prostheses and overdentures in the edentulous m and ible in a r and omized prospect i ve study of treatment results , clinical working hours , laboratory working hours , and laboratory costs including material s. MATERIAL S AND METHODS Seventeen subjects agreed to participate . Three st and ard Brånemark implants were placed between the mental foramina in each patient . After the connection of st and ard abutments , subjects were r and omly assigned to the fixed prosthesis group ( n = 11 ) or overdenture group ( n = 6 ) . Subjects in the fixed group were provided with prostheses according to the All-in-One concept . Subjects in the overdenture group received a conventional denture retained by a Dolder bar system . RESULTS One implant was lost in the fixed prosthesis group after 1 year . A new implant was placed , and the prosthesis was refitted . Mean clinical working hours were 3.1 in the fixed prosthesis group and 4.1 in the overdenture group . Mean laboratory working hours were 12.5 in the fixed prosthesis group and 7.7 in the overdenture group . Total laboratory costs , including material s , were on average about 1,700 US dollars for the fixed prosthesis and 1,350 US dollars for the overdenture . CONCLUSION A fixed implant-supported prosthesis in the edentulous m and ible could be provided at about the same cost as an overdenture using the method described . Provided that the early survival results prove to be long lasting , the choice between a fixed and a removable prosthesis need not be a matter of economy The loss of natural teeth compromises chewing efficiency , and edentulous patients often have a diet that is deficient in fibre and vitamins . Prostheses that are retained on implants offer the possibility of overcoming some of the limitations of conventional dentures in terms of chewing efficiency . The aim of this study was to test the hypothesis that improvement in satisfaction with oral prostheses would result in improved food selection in edentulous patients . This prospect i ve study involved three groups , namely ( i ) subjects who requested and received implants to stabilise a complete fixed or removable prosthesis ( IG , n = 26 ) , ( ii ) edentulous subjects who requested implant prostheses , but received conventional dentures ( CDG1 , n = 22 ) , and ( iii ) edentulous subjects who requested and received conventional dentures ( CDG2 , n = 35 ) . Data were collected using vali date d question naires pre- and postoperatively . Prior to treatment , all subjects were asked whether they ate a variety of hard and soft foods , to indicate the degree of difficulty they experienced when chewing these foods , and to rate their satisfaction with various aspects of their maxillary and m and ibular complete dentures . Following the completion of treatment , subjects completed the question naires again . Pre- and postoperative data were compared . Subjects who received implant prostheses reported significant improvement in chewing hard and soft foods . CDG2 subjects also reported improvement , but CDG1 subjects reported no change or even deterioration following treatment . Despite reported improvement in satisfaction with comfort and ability to chew food , 30 - 50 % of IG and CDG2 subjects still avoided eating foods such as carrot and apple . This suggests that , in the absence of tailored dietary advice , apparently successful prosthetic rehabilitation does not necessarily result in a satisfactory diet OBJECTIVE The objective is to compare , in a prospect i ve r and omized clinical trial , three types of attachment systems for m and ibular implant overdenture , focusing on costs , maintenance requirements and complications from baseline to the end of 5-year follow-up period . MATERIAL S AND METHODS Sixty-nine fully m and ibular and fully/partially maxillary edentulous patients received two screw-type Straumann implants , in the m and ibular canine region . New overdentures with three types of attachment systems were inserted according to an early-loading protocol : Group B ( balls , divided into Subgroup B.1 - retentive anchor with gold matrix and Subgroup B.2 - retentive anchor with titanium matrix ) ( n = 23 ) , Group M ( magnets ) ( n = 23 ) and Group L ( locator ) ( n = 23 ) . RESULTS The highest maintenance event number ( 195 ) was observed in Group B vs. 31 in Group L and 15 in Group M. Significantly more complications were recorded in Subgroup B.1 than in Subgroup B.2 , Group M and Group L ( P < 0.05 ) . Group M registered the highest prosthetic success ( 82.6 % ) in the 5 years , followed by Group L ( 78.2 % ) . Subgroup B.1 had the lowest success rate ( 50 % ) . The magnet group recorded statistically significant higher costs , comparing with the other two groups ( P < 0.05 ) . CONCLUSIONS The three attachment systems functioned well after 5 years . The magnets had a low maintenance requirement and high success rate , despite the relatively increased initial costs . Retentive anchor with titanium matrix and locator may be a better choice from a financial point of view , taking into consideration the initial low cost of the components and also the reduced number of complications PURPOSE Edentulous patients with denture problems benefit from implant treatment with overdenture prostheses . The aim of this prospect i ve study was to investigate a method of analyzing cost effectiveness in dentistry . As an example , overdenture treatment with two or four implants was compared to the conventional complete denture ( CD ) . MATERIAL S AND METHODS In a self-selected trial , 20 patients each were treated with implant-retained overdentures ( two implants , IRET ) , implant-supported overdentures ( four implants , ISUP ) , or CDs ( control group ) in the edentulous m and ible . A cost-effectiveness analysis was performed from the patient 's perspective , with a time horizon of 6 months . Direct health-care costs were calculated in Swiss Francs ( in 2000 ) , and effects were defined as improvements in perceived chewing ability compared with the baseline value before treatment ( measured on a VAS ) . Point estimates for mean incremental cost-effectiveness ratios were complemented with cost-effectiveness acceptability curves to account for uncertainties associated with costs and effects . RESULTS Mean incremental costs were CHF 4,329 ( IRET-CD ) , CHF 13,360 ( ISUP-CD ) , and CHF 9,031 ( ISUP-IRET ) ; these cost differences were all statistically significant . The mean incremental effects at 6 months were 19 % ( IRET-CD ) , 23 % ( ISUP-CD ) , and 4 % ( ISUP-IRET ) . Incremental cost-effectiveness ratios were CHF 228 ( IRET-CD ) , CHF 581 ( ISUP-CD ) , and CHF 2,258 ( IRET-ISUP ) per percentage increase in chewing ability . CONCLUSION From an economic point of view , IRETs were more attractive than ISUPs . The latter were associated with a statistically significant improvement in perceived chewing ability compared to CDs , but at substantially higher costs PURPOSE This article compares the cost of m and ibular two-implant overdenture treatment to that of conventional denture treatment in an academic teaching hospital . MATERIAL S AND METHODS Sixty edentulous patients ( aged 65 to 75 years ) participated in a r and omized clinical trial . All patients received a new maxillary complete denture and either a m and ibular conventional denture ( n = 30 ) or an implant overdenture on two unsplinted implants ( n = 30 ) . Re source -based microcosting of direct and indirect costs ( eg , expenses and time cost to patients ) of all scheduled and unscheduled visits was conducted through 1 year following delivery of the prostheses . RESULTS Mean direct costs ( 1999 CD dollars ) for scheduled visits in the implant and conventional groups were 2,332 dollars and 814 dollars , respectively , and mean indirect costs were 1,150 dollars and 810 dollars , respectively . Differences between the two groups were significant . Twenty-six patients in each group had unscheduled visits during the study at a median direct cost for the overdentures of 85 dollars and 64 dollars for the conventional dentures . Median indirect costs for unscheduled visits were 163 dollars and 202 dollars , respectively . These differences were not significant . Mean total costs of the overdentures were 4,245 dollars and 2,316 dollars for the conventional dentures , and the between-group difference was significant . CONCLUSION The direct cost of m and ibular two-implant overdenture treatment was 2.4 times higher than that of conventional denture treatment . When indirect costs were added , the implant-to-conventional total cost ratio estimate was 1.8 . These cost data can now be combined with estimates of the efficacy of the two types of prosthesis so practitioners and patients can make informed decisions about these prosthodontic treatment concepts PURPOSE The aim of this prospect i ve study was to report long-term treatment outcomes ( prosthetic and implant related ) of edentulous patients treated with implant-supported fixed prostheses who participated in the first clinical implant study in North America . MATERIAL S AND METHODS Forty-five patients were treated with Brånemark implants supporting a total of 47 fixed prostheses ( 42 m and ibular and 5 maxillary ) between 1979 and 1984 . All patients were recalled regularly for comprehensive prospect i ve clinical and radiographic assessment s. RESULTS Thirty-one patients ( 33 prostheses ) attended a final recall visit in 2002 ; 71 % of patients had been followed for 20 years ( range 18 to 23 years ) , with overall prosthetic plan and implant outcome success rates of 84 % and 87 % , respectively . Mean marginal bone loss around the implants after the first year of loading was small ( 0.05 mm/year ) , with high individual variations . Poor oral hygiene , smoking history , and implant position appeared to be predictors of marginal bone loss . Prosthetic maintenance was ongoing and included fractured components and replacement of prostheses ; the longevity of a fixed prosthesis for this group of patients was 8.39+/-5.30 years . CONCLUSION This study confirmed the overall long-term treatment outcome success of patients treated with fixed prostheses supported by Brånemark implants . Successful osseointegration with a small mean bone loss was maintained as study patients aged , although prosthetic maintenance was required . The latter consideration should be discussed with all patients seeking such treatment |
10,374 | 23,860,901 | Conclusions Evidence proving the effectiveness of NCCM as an adjunct to unsupervised oral hygiene for plaque and gingivitis control is still insufficient .
Clinical relevance This review provides an overview of the strength of clinical evidence regarding the effectiveness of natural compounds containing mouthrinses in promoting gingival health | Objectives To evaluate the effectiveness of natural compounds containing mouthrinse ( NCCM ) as an adjunct to unsupervised oral hygiene in the management of dental plaque and gingivitis . | It is well known that gingivitis is a bacterially-elicited inflammation of the marginal gingiva . A number of chemical agents have been evaluated over the years with regard to their antimicrobial effects in the oral cavity ; however , all are associated with side effects that prohibit regular long-term use . Therefore , the effectiveness of a natural Mexican Sanguinaria extract ( Polygonum aviculare L. ) against gingivitis , was assessed in 60 male dentistry students between the ages of 18 and 25 years . Over a period of 2 weeks , these students used the Sanguinaria extract ( 1 mg/ml ) in oral rinse twice daily as a unique oral health measurement ( no tooth-brushing was allowed ) . The O'Leary Plaque Index and the Löe and Silness Gingivitis Index were recorded at baseline ( day 0 ) in all the subjects . Also , a complete prophylaxis was performed after both indices were obtained . The antibacterial and antiinflammatory effects of the extract were evaluated on days 7 , 11 and 14 . The results showed that the Mexican Sanguinaria extract in oral rinse significantly decreased gingivitis from day 0 ( -x=1 . 056 ) to day 14 ( -x=1.011 ) ( P</=0.05 ) . In contrast , a significant increase in dental plaque was observed from day 0 ( -x=91.38 ) to day 14 ( -x=98.69 ) ( P</=0.05 ) ; however , the consistency of this plaque permitted its mechanical flushing easily . From this study , it is concluded that the Mexican Sanguinaria extract in oral rinse can be employed supportively in the therapy of gingivitis The purpose of the present study was to establish in vitro the inhibiting effect of a herbal extract mixture on a selected number of micro-organisms and to test in vivo the effect of a mouthwash containing 6.3 mg/ml herbal extract mixture on plaque and gingivitis as compared to a minus active control mouthrinse . The herbal extract was a mixture of : Juniperus communis ( juniper ) , Urtica dioca ( nettle ) , Achillaea millefolium ( yarrow ) ; 1:1:1 . In the study , in-vitro , the effect of pure herbal extract mixture on acid production of Streptococcus mutans was tested and the minimum inhibitory concentrations ( MIC ) of the following micro-organisms were tested : Streptococcus mutans , Streptococcus mitis , Actynomyces viscosus , Actynomyces naeslundii , Actinobacillus actinomycetemcomitans , Prevotella intermedia , Campylobacter rectus , Fusobacterium nucleatum , Veillonella parvula . The MIC-values for A. viscosus and P. gingivalis were 100 mg/ml . The MIC-values for A. naeslundii and A. actinomycetemcomitans were considerably lower ( 10 mg/ml ) . S. mitis was the most susceptible of the tested organisms to the extract with a MIC value of 1 mg/ml . S. mutans , C. rectus , V. parvula , and F. nucleatum were not influenced by the extracts . No inhibitory effect of the 6.3 mg/ml herbal extract mixture was observed on the acid production of S. mutans . For the study in-vivo , 45 volunteers were selected on the basis of having moderate gingival inflammation . As efficacy parameters the plaque index , modified gingival index and angulated bleeding index were assessed . The subjects were r and omly divided among 3 experimental groups ( 2x test and 1 ' minus active ' control ) . The participants were requested to rinse with 10 ml of mouthwash twice a day for a period of three months . After 6 weeks and 3 months , the same clinical indices as at baseline were recorded . The results show no difference between the two test groups and the control group . In conclusion , the results of the present study have shown that the mixture of the 3 herbal extracts , Juniperus communis , Urtica dioca and Achillaea millefolium when used in a mouthrinse has no effect on plaque growth and gingival health Background : The key to good oral health is hidden in nature . Natural herbs like neem , tulsi , pudina , clove oil , ajwain , triphala and many more has been used since ages either as a whole single herb or as a combination against various oral health problems like bleeding gums , halitosis , mouth ulcers and preventing tooth decay . The aim of the study was to compare the efficacy of a commercially available herbal mouthrinse ( Herboral ) with that of chlorhexidine gluconate which is considered to be a gold st and ard as an anti-plaque agent . Material s and Methods : A r and omized , two-group , parallel study as a ‘ de novo ’ plaque accumulation model was carried out on 50 subjects ( 23 males and 27 females ) . At baseline , all participants received a professional prophylaxis and were r and omly assigned to the test ( Herbal mouthrinse ) and control ( Chlorhexidine Gluconate ) group . On the following three days , all subjects rinsed with 10 ml of the allocated mouthrinse twice daily for 1 min . They were asked to refrain from use of any other oral hygiene measures during the study . At the end of the experimental period , plaque was assessed and a question naire was filled by all subjects . Results : Chlorhexidine ( mean plaque score=1.65 ) inhibited plaque growth significantly more than the herbal mouthrinse ( mean plaque score=1.43 , P<0.001 ) . The results of the question naire showed that Herboral was preferred by patients for its taste , its convenience of use and taste duration ( aftertaste ) . However , Chlorhexidine was considered to be more effective in reducing plaque as compared to Herboral . Conclusion : Herbal mouthrinse was found to be a potent plaque inhibitor , though less effective than Chlorhexidine Gluconate . However , it can serve as a good alternative for the patients with special needs as in case of diabetics , xerostomics , and so on Background The aim of this study was to evaluate the antiplaque effect of a new alcohol free essential oil mouthwash with respect to a control of an essential oil with alcohol mouthwash , using an in vivo plaque regrowth model of 3-days . Methods The study was design ed as a double-masked , r and omized , crossover clinical trial , involving 30 volunteers to compare two different essential oil containing mouthwashes , during a 3-day plaque accumulation model . After receiving a thorough professional prophylaxis at the baseline , over the next 3-days each volunteer refrained from all oral hygiene measures and had two daily rinses with 20 ml of the test mouthwash ( alcohol free essential oil ) or the control mouthwash ( essential oil with alcohol ) . At the end of the each experimental period , plaque was assessed and the panelists filled out a question naire . Each subject underwent a 14 days washout period and there was a second allocation . Results The essential oil mouthwash with ethanol shows a better inhibitory effect of plaque regrowth in 3-days than the mouthwash test with only essential oil in the whole mouth ( plaque index = 2.18 against 2.46 , respectively , p < 0.05 ) ; for the lower jaw ( plaque index = 2.28 against 2.57 , respectively , p < 0.05 ) ; for the upper jaw ( plaque index = 2.08 against 2.35 , respectively , p < 0.05 ) ; for the incisors ( plaque index = 1.93 against 2.27 , respectively , p < 0.05 ) ; and the canines ( plaque index = 1.99 against 2.47 , respectively , p < 0.05 ) . Conclusion The essential oil containing mouthwash without alcohol seems to have a less inhibiting effect on the plaque regrowth than the traditional alcoholic solution . Trial Registration Clinical Trials.gov PURPOSE The purpose of this study was to determine the effects of two oral rinses-one 0.12 % chlorhexidine rinse ( CHX ) and one herbal rinse (HBR)-on gingival health status over time . METHODS Sixty-three participants were r and omly assigned to one of three treatment groups : CHX , HBR , or placebo . For three months , participants rinsed twice daily ( morning and evening ) with ( 1/2 ) ounce of allocated rinse after brushing and flossing . Individuals were given the same type of soft bristle toothbrush and whitening toothpaste . No attempt was made to modify participants ' routine oral care , except they were advised to refrain from use of any other oral rinse for the duration of the study . Data were collected at baseline ( B ) , month one ( 1 ) , two ( 2 ) , and three ( 3 ) utilizing the Gingival Index ( GI ) , Plaque Index ( PI ) , and bleeding on probing ( BOP ) . A full mouth periodontal probing was performed at baseline and at the completion of the study . A soft tissue oral assessment was completed at each visit . CHX , HBR , and placebo data were compared between three time intervals , B-1 , B-2 , and B-3 . Statistical analysis was conducted by means of multiple regression using generalized linear models . Paired comparison tests -- ANOVA followed by a post hoc Tukey test -- were used to confirm results . RESULTS CHX was the only oral rinse to demonstrate a statistically significant effect on the reduction of mean GI , BOP , and PI scores when compared to placebo . CHX demonstrated a 31 % reduction in the proportion of GI scores between B-2 and a 29 % reduction between B-3 ( p=.003 and p=.012 , respectively ) . CHX demonstrated a 19 % reduction of BOP sites between B-1 , 32 % reduction between B-2 , and 29 % reduction between B-3 ( p=.028 , p=.000 , and p=.005 , respectively ) . CHX demonstrated a 20 % reduction in PI scores between B-1 , and a 28 % reduction between B-2 ( p=.005 and p=.032 , respectively ) . The effects of HBR on reducing mean GI , BOP , and PI scores were not statistically greater than placebo at any time during the study OBJECTIVE The purpose of the present investigation was to determine if antimicrobial mouthrinses with different formulations could affect the composition of the subgingival microbiota and clinical parameters of adjacent tissues in periodontal maintenance subjects . METHODS One-hundred and sixteen subjects , who had been treated for chronic periodontitis and were in a maintenance program , were r and omly assigned one of four mouthrinses , to be used twice daily for three months . The mouthrinses were herbal 1 , herbal 2 , essential oil , and chlorhexidine . Clinical measurements and subgingival plaque sample s were taken at baseline and at three months . Plaque sample s were individually evaluated for 18 test species/taxa using checkerboard DNA-DNA hybridization . Significance of differences between baseline and three months for both microbiological and clinical parameters were determined using the Wilcoxon Signed Ranks test . Significance of difference among groups for change in clinical and microbiological parameters was determined using analysis of covariance ( ANCOVA ) , adjusting for baseline values . RESULTS Shifts in species proportions differed significantly for 9/18 test species/taxa among the four mouthrinse groups . Streptococcus and Capnocytophaga species were reduced most in the herbal rinse groups , while Veillonella parvula was reduced most in the essential oil and chlorhexidine groups . Actinomyces were also markedly reduced in the chlorhexidine group . Mean Plaque ( PI ) and Gingival Indices ( GI ) were reduced between baseline and three months in each group . Results emphasize that chlorhexidine ( p < 0.001 ) and herbal ( p < 0.05 ) rinses significantly reduced PI . Some subjects in each group responded better than others . CONCLUSION All four mouthrinses tested produced shifts in the composition of subgingival microbiota , although the results differed among the groups . The observed microbial changes were accompanied by improvements in clinical parameters in the periodontal maintenance subjects In the treatment of periodontal disease initial therapy aims at reducing marginal inflammation so allowing assessment of residual disease and further treatment options . The aim of the present study was to determine whether the use of a dentifrice and oral rinse containing sanguinaria extract led to a more rapid resolution of gingival inflammation following initial therapy . Thirty-four subjects , r and omly assigned to one of two treatment groups , took part in this r and omized double-blind parallel study . All subjects received initial therapy including oral hygiene instruction and scaling and root planing as required . One group also received an active dentifrice and oral rinse containing sanguinaria extract ( an antiplaque agent ) and zinc chloride . The other group received a placebo dentifrice and oral rinse . The gingival index ( GI ) , plaque index ( PLI ) and probing pocket depths ( PD ) were recorded at six sites per tooth at baseline , two weeks after initial therapy and six weeks after initial therapy . There was no significant difference between the groups for any of the parameters at the baseline examination . Two weeks following initial therapy both groups showed a statistically significant increase in the number of sites with PLI of 0 or 1 ( p < 0.0001 ) and a statistically significant increase in the number of sites with a GI of 0 or 1 ( that is , no bleeding on probing ) , ( p < 0.0001 ) . Also there was a statistically significant increase in the number of sites with probing depths < or = 3 mm ( p < 0.0001 ) compared with baseline . These changes were maintained through to six weeks post therapy . There was no significant advantage to the sanguinaria group . Results demonstrate that initial therapy in the form of oral hygiene instruction , scaling and root planing leads to a significant improvement in periodontal status which is maintained at least in the short term . Further , use of a dentifrice and oral rinse containing sanguinaria did not improve the efficacy of initial therapy PURPOSE Several antiplaque agents are being available in the market in spite of vast development of modern medical science , satisfactory treatment of ' oral diseases ' by newer drugs is not fully achieved , rather the chemical compounds has exposed the patients to it is different ill effects , therefore , there is interest to find out effective remedy of any disease by harmless herbal drugs thus the aim of this study was to compare plaque formation at 24 hours after the use of Triphala , Hi ora , Chlorhexidine and Colgate Plax mouth washes . METHODS A controlled , r and omized , double-blind , crossover clinical trial was design ed . Thirty subjects underwent four consecutive experimental phases with four treatments : Triphala , Hi Ora , Chlorhexidine and Colgate Plax . On the day of study , the subjects discontinued all other oral hygiene habits and were r and omly assigned for treatment with the experimental mouthwash . Each experimental phase was preceded by a 28-day washout period . Plaque formation was recorded after one undisturbed day . RESULTS Triphala , Hi Ora and Chlorhexidine reduced de novo plaque formation to a greater extent than the colgate plax mouthwash ( p < 0.05 ) . CONCLUSION Triphala and Hi Ora presents an anti-plaque efficacy similar to that of chlorhexdine , and was more effective at inhibiting plaque formation than the Colgate Plax mouth wash AIM To compare the efficacy of turmeric mouthwash and chlorhexidine gluconate mouthwash in prevention of gingivitis and plaque formation . MATERIAL S AND METHODS A total of 100 r and omly selected subjects visiting the Department of Periodontology at Bharati Vidyapeeth Deemed University , Dental College and Hospital , were considered for the study . The gingival index ( GI ) by Loe and Silness was recorded which was followed by Turesky- Gilmore-Glickman modification of Quigley Hein plaque index ( TQHPI ) at 0 , 14 and 21 days . Individuals who gave an informed consent , subjects in the age group of 25 to 35 years with having fair and poor gingival index scores and a score > 1 for plaque index , were included in the study . RESULTS Results showed statistically significant reduction ( p < 0.05 ) in mean plaque index ( PI ) with chlorhexidine gluconate mouthwash when compared with turmeric mouthwash . No significant difference in mean gingival index ( GI ) was seen when chlorhexidine mouthwash was compared with turmeric mouthwash . Significant reduction in total microbial count ( p < 0.05 ) was observed in both the groups . No significant difference was observed in total microbial count when chlorhexidine mouthwash was compared with turmeric mouthwash . CONCLUSION From the above observations , it can be concluded that chlorhexidine gluconate as well as turmeric mouthwash can be effectively used as an adjunct to mechanical plaque control methods in prevention of plaque and gingivitis . Chlorhexidine gluconate has been found to be more effective when antiplaque property was considered . CLINICAL SIGNIFICANCE From this study , it could be stated that turmeric is definitely a good adjunct to mechanical plaque control . Further studies are required on turmeric based mouthwash to establish it as a low cost plaque control measure Several different plant extracts have been evaluated with respect to their antimicrobial effects against oral pathogens and for reduction of gingivitis . Given that a large number of these substances have been associated with significant side effects that contraindicate their long-term use , new compounds need to be tested . The aim of this study was to assess the short-term safety and efficacy of a Lippia sidoides ( " alecrim pimenta")-based essential oil mouthrinse on gingival inflammation and bacterial plaque . Fifty-five patients were enrolled into a pilot , double-blinded , r and omized , parallel-armed study . Patients were r and omly assigned to undergo a 7-day treatment regimen with either the L. sidoides-based mouthrinse or 0.12 % chlorhexidine mouthrinse . The results demonstrated decreased plaque index , gingival index and gingival bleeding index scores at 7 days , as compared to baseline . There was no statistically significance difference ( p>0.05 ) between test and control groups for any of the clinical parameters assessed throughout the study . Adverse events were mild and transient . The findings of this study demonstrated that the L. sidoides-based mouthrinse was safe and efficacious in reducing bacterial plaque and gingival inflammation The effectiveness of medicinal herbs in both a toothpaste and oral rinse on dental plaque , sulcus bleeding , and the pH of total saliva was investigated in a single-blind study on 50 dentistry students between the ages of 23 and 28 years . Over a period of 4 weeks , 25 students used either placebo or preparations containing medicinal herbs . Parameters measured were the approximal plaque index ( API ) and sulcus bleeding index ( SBI ) . These were determined at the same time of day ( 12:00 P.M. ) , the last food intake having occurred at least 1 hour previously . Compared with the placebo preparations , the herbal ingredients significantly reduced both the API ( initial value : 40.8 % , final value : 23.9 % ) and the SBI ( initial value : 33.4 % , final value : 18.6 % ) . The pH of the total saliva was significantly displaced into the alkaline range by the application of the herbal products , whereas the placebo products had a contrary effect . The results of this study suggest that herbal ingredients can be employed supportively in the therapy of periodontal diseases and for routine prophylaxis BACKGROUND Glucosyltransferases ( GTF ) play an important role in the adherence of bacteria to acquired pellicle . Cocoa bean husk extract ( CBHE ) has been shown to possess anti-glucosyltransferase and antibacterial activity . AIM This study aim ed to evaluate the effect of CBHE on plaque accumulation and mutans streptococcus count when used as a mouth rinse by children . MATERIAL S AND METHODS Scaling of the teeth of the selected children was done and the children were instructed to refrain from their routine oral hygiene practice s till the morning of the fourth day ; they were instead given a placebo mouth rinse for use during this period . On the fourth day , saliva was collected from each subject for microbiological analysis and plaque was disclosed and scored using the modified Quigley and Hein plaque index ; later , the teeth were cleaned . After 1 week , scaling of the subjects was done and they were given CBHE mouth rinse to rinse their mouth , following the above protocol . The data was statistically analyzed using Wilcoxon 's signed rank test . RESULTS There was a 20.9 % decrease in mutans streptococci counts and a 49.6 % decrease in plaque scores in the CBHE group as compared to the placebo group , which was highly significant ( P value Conclusion : CBHE is highly effective in reducing mutans streptococci counts and plaque deposition when used as a mouth rinse by children AIM The effect of Ocimum gratissimum ( Og ) on the reduction of dental plaque and gingivitis was evaluated in a r and omized , parallel and double-blind clinical trial . MATERIAL S AND METHODS Subjects were r and omly allocated to the control group (n=10)-mouth rinse with no antiseptic agents ; CLX group (n=10)-mouth rinse containing chlorhexidine digluconate or Og group (n=10)-mouth rinse containing Ocimum gratissimum . Plaque ( PLI ) and bleeding ( BI ) indexes were assessed at days 0 and after 3 months . Subjects were asked to brush their teeth with a fluori date d dentifrice , three times a day , during a 90-day period . After each brushing they rinsed with one of the three mouth rinses during 1 minute . RESULTS There was a significant reduction on plaque and gingivitis in tests groups ( p < 0.05 ) , but no statistically significant difference was observed among them ( p > 0.05 ) . CONCLUSION Mouth rinse containing Og was effective as antiplaque and antigingivitis agent , in a similar manner that chlorhexidine digluconate . CLINICAL SIGNIFICANCE Research in treatment of chronic oral diseases using natural agents must be encouraged to verify which would be a useful addition to the current range of chemotherapeutic treatment options A double-blind study evaluated the effects of systemic and topical folate on gingival inflammation during the fourth and eighth months of pregnancy . Thirty women were r and omly divided into three groups . Group A received placebo mouthwash and tablets ; Group B ; placebo mouthwash and 5 mg folate tablets ; Group C : folate mouthwash and placebo tablets . Supplementation lasted for 14 days during months 4 and 8 . Subjects took one tablet daily and rinsed twice daily for 1 min with the mouthwash . At the start and finish of each 14-day period , fasting serum and red cell folate levels were estimated and oral status assessed by a plaque index ( P1I ) , a gingival index ( GI ) , and gingival exu date flow meter ( GEF ) . Subjects completed 1-week diet sheets which were analysed for dietary folate . All groups were similar in each parameter at the start . Correlation was demonstrated between GI and P1I , and between GI and GEF . GI tended to increase throughout pregnancy in all groups except Group C , when in the eighth month there was a highly significant improvement ( 0.001 less than P 0.01 ) despite no significant change in P1I . Although dietary intake of folate was significantly higher during the eighth month in Group C as compared with Groups A and B , ( 0.001 less than P less than 0.01 ) , the folate mouthwash produced highly significantly improvement in gingival health in pregnancy AIM To compare the cleaning effectiveness of chamomile hydroalcoholic extract and tea tree oil to 2.5 % sodium hypochlorite ( NaOCl ) solution as an intracanal irrigant for the removal of the smear layer . METHODOLOGY Forty extracted , single-rooted , mature , permanent , human teeth were allocated at r and om into one of three experimental groups of ten teeth and two control groups of five teeth . For each tooth , the pulp chamber was accessed and the canal prepared using K-type files and Gates-Glidden burs , using a step-back technique ; the apical stop was prepared to a size 30 . Each canal was subsequently irrigated with one of the following solutions : distilled water ( as a negative control ) , 2.5 % NaOCl + 17 % ethylenediamine tetraacetic acid ( EDTA ) ( as a positive control ) , chamomile or tea tree oil or 2.5 % NaOCl . Each tooth was split longitudinally and prepared for examination by scanning electron microscopy ( SEM ) . The quantity of smear layer remaining on the three levels of each canal ( coronal , middle and apical ) was examined using magnifications of 2000 and 5000x . The data were analysed using nonparametric Kruskal-Wallis and Mann-Whitney U-tests . RESULTS The most effective removal of smear layer occurred with the use of NaOCl with a final rinse of 17 % EDTA ( negative control ) followed by the use of a chamomile extract . Chamomile extract was found to be significantly more effective than distilled water and tea tree oil ( P < 0.008 ) . The use of a 2.5 % NaOCl solution alone , without EDTA and that of tea tree oil , was found to have only minor effects . There was no statistical difference between distilled water , 2.5 % NaOCl and tea tree oil . CONCLUSIONS The efficacy of chamomile to remove smear layer was superior to NaOCl alone but less than NaOCl combined with EDTA The main objective was to investigate whether low-molecular-weight fraction of edible mushroom shiitake extract ( Lentinus edodes ) possesses caries-preventive properties . The study was design ed as a double-blind , three-leg , cross-over , r and omized , controlled clinical trial carried out on two series of volunteers at the University of Gothenburg , and the Academic Centre for Dentistry Amsterdam . Volunteers rinsed twice daily with a solution containing low-molecular-weight fraction of edible mushroom , placebo ( negative control without active ingredients ) , or Meridol ( positive control , AmF-SnF2 ) for two weeks , with a two-week washout period between each rinsing period . Changes in the acidogenicity of dental plaque before and after a sucrose challenge , shifts in microbial composition , and plaque scores were determined . Frequent rinses with shiitake reduced the metabolic activity of dental plaque . No reduction of plaque scores and no inhibition of the production of organic acids in plaque was found . Minor differences in microbial composition between test sessions were found . To conclude , the results indicate that shiitake extract has anticariogenic potential , but not to the same extent as the positive control The inhibitory effect of oolong tea extract ( OTE ) containing polymerized polyphenols on plaque deposition was examined in 35 human volunteers . Thirty-five human volunteers , aged 18 - 29 years , who received extensive oral prophylactic procedures were requested to refrain from all oral hygiene procedures for 4 days , and to rinse their mouth with 0.5 mg/ml OTE solution in 0.2 % ethanol before and after every intake of food and before sleeping at night . No restriction regarding meals was given during the test period , except to refrain from teas or coffee . Plaque deposition was evaluated after disclosing the teeth with Erythrocin at the termination of this experiment . The study was repeated 1 week after the first trial , but only 0.2 % ethanol without OTE was used for mouthrinsing in the second trial . OTE was found to significantly inhibit plaque deposition in volunteers , although mouthrinsing with OTE solution had no significant effect on the number of mutans streptococci in unstimulated whole saliva A single-blind crossover study was used to compare the ability of a 0.2 % chlorhexidine mouthrinse ( Corsodyl ) with a sanguinarine-zinc mouthrinse ( Veadent ) to inhibit plaque and gingivitis . 14 volunteers starting with plaque-free mouths and optimal gingival health , rinsed with the preparations over two 19-day periods whilst refraining from all other oral hygiene procedures . At days 8 , 15 and 19 of the trial , Corsodyl was significantly more effective at inhibiting both plaque and gingivitis . The findings of this study would suggest that the Veadent mouthrinse would at most only have a limited rôle as an inhibitor of plaque and gingivitis OBJECTIVE to evaluate the effect of a pomegranate-containing mouthrinse on plaque , determine whether it has any adverse effects , and evaluate its antibacterial properties against selected periodontopathogens in vitro . METHOD AND MATERIAL S thirty periodontally healthy volunteers , r and omly divided into three groups , refrained from all mechanical oral hygiene measures for 4 days and used one of the r and omly assigned mouthrinses ( A , pomegranate ; B , chlorhexidine ; or C , distilled water [ placebo ] ) twice daily . The Plaque Index ( PI ) was assessed at days 0 and 5 . Adverse effects were also evaluated . Pomegranate extract was tested against Aggregatibacter actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , and Prevotella intermedia ( P.i . ) . RESULTS in all groups , the PI significantly increased from the baseline to day 5 ( P < .1 ) . The pomegranate mouthrinse created no adverse effects . There was a statistically significant difference ( P < .05 ) between the chlorhexidine and placebo rinse and the pomegranate and placebo rinse , but no statistically significant difference was found between the chlorhexidine and pomegranate rinse with respect to the PI . Pomegranate extract showed inhibition of all three strains of periodontopathogens at various concentrations . CONCLUSION these results indicate that the pomegranate mouthrinse has an antiplaque effect . Pomegranate extract is efficacious against A.a . , P.g . , and P.i . strains in vitro . Pomegranate mouthrinse should be explored as a long-term antiplaque rinse with prophylactic benefits AIM This study compared the oral health efficacy of Persica mouthwash ( containing an extract of Salvadora persica ) with that of a placebo . DESIGN In a double-blind , cross-over trial , participants were r and omly allocated to use either the Persica mouthwash or a placebo for a three-week period . Plaque accumulation , gingival bleeding and the salivary concentrations of mutans streptococci ( MS ) were measured before and immediately following the experimental period . After an eight-week ' washout ' period , the study was repeated with participants using the alternative mouthwash . PARTICIPANTS Twenty-eight healthy students ( aged between 18 and 42 years ) volunteered to take part in this investigation . RESULTS Compared with the pre-treatment values , both placebo and experimental groups demonstrated significantly reduced gingival bleeding ( p < 0.01 ) . Plaque scores were not significantly reduced following use of either Persica or the placebo . However , the use of Persica , but not the placebo , result ed in significant reduction in the carriage of MS ( p < 0.05 ) . CONCLUSION Use of Persica mouthwash result ed in improved gingival health and lower carriage rate of cariogenic bacteria when compared with the pre-treatment values . The placebo ( vehicle control ) also improved gingival health significantly . Neither the Persica nor the placebo reduced the accumulation of dental plaque The present clinical trial was performed to assess the effect of a Sanguinarine-containing mouthrinse on developing plaque and gingivitis in man . The trial was design ed as a blind cross-over study . The active mouthrinse consisted of a 0.03 % aqueous solution of Sanguinaria extract ; an aqueous solution with similar color and taste as the active rinse was used as the placebo preparation . 14 dental students participated in the trial . At the start of each of 2 test phases , their gingival conditions were normal and their tooth surfaces free from dental plaque . Following a baseline examination , the participants refrained from mechanical tooth cleaning measures for 2 weeks . They rinsed twice daily with either the active or the placebo mouthrinse . Clinical examinations of plaque and gingivitis were repeated after 4 , 7 and 14 days use of the mouthrinse preparation . During the second test phase of no mechanical tooth cleaning , the subjects who previously had rinsed with the placebo solution now used the active compound and vice versa . The results demonstrated that the Sanguinarine-containing mouthrinse was effective in reducing plaque formation and retarding the development of gingivitis The purpose of this study was to test the efficacy and safety of sanguinaria-containing regimens with and without fluoride using the American Dental Association guidelines for evaluating chemotherapeutic agents . The study was a 6-month , double-blind , 4-cell , placebo-controlled , parallel investigation involving 120 subjects . Following screening procedures , subjects were r and omly assigned to 4 groups . Group 1 received a dentifrice containing 0.075 % sanguinaria extract ( SaE ) and 2.0 % zinc chloride ( ZnCl2 ) in a dicalcium phosphate base , plus an oral rinse containing 0.03 % SaE and 0.2 % ZnCl2 . Group 2 received identical products without SaE or ZnCl2 . Group 3 received a dentifrice containing 0.8 % sodium monofluorophosphate , 0.075 % SaE , and 0.05 % ZnCl2 in a silica base , plus an oral rinse containing 0.03 % SaE and 0.2 % ZnCl2 . Group 4 products were identical to those of Group 3 but without SaE and ZnCl2 . Supragingival plaque and gingival inflammation were scored at 0 , 1 , 2 , 1.5 , 3 , 4.5 , and 6 months ; bleeding upon probing was measured at 1 , 1.5 , 3 , and 6 months . Microbiological sample s were taken from plaque , tongue , and cheek areas . The active products produced statistically significantly lower scores than the placebo agents for all indices ( P less than .0001 ) . Six-month plaque scores were 13.1 % lower for Group 1 and 17.4 % lower for Group 3 compared to placebo products . When the Plaque Severity Index was applied , the percentage reductions were 33 % for Group 1 and 41 % for Group 3 compared to placebos . Gingival inflammation scores were 16.7 % lower for Group 1 and 18.1 % lower for Group 3 at 6 months compared to placebo scores . ( ABSTRACT TRUNCATED AT 250 WORDS The effects of sanguinaria extract and zinc chloride on plaque growth and gingivitis inhibition were assessed on subjects with initially plaque-free tooth surfaces using a series of oral rinses in a single-blind , crossover , no-oral-hygiene study lasting 2 weeks . A placebo oral rinse containing no sanguinaria or zinc chloride ( A ) , and test rinses containing 150 micrograms/ml sanguinaria and 0.2 % zinc chloride ( B ) , 300 micrograms/ml sanguinaria and no zinc chloride ( C ) , and 300 micrograms/ml sanguinaria and 0.2 % zinc chloride ( D ) were evaluated . Subjects using the higher concentration rinses C and D had significantly lower plaque scores than rinse A at 7 and 14 days ( p less than 0.05 for C , p less than 0.01 for D ) . However , groups C and D were not significantly different from each other . Group D had significantly lower plaque ( p less than 0.05 ) and gingivitis ( p less than 0.01 ) scores than group B. Subjects who used rinse B and placebo rinse A had the highest plaque and gingivitis scores and comparison of these two groups revealed no significant difference . At the end of 14 days , the % distribution of 0 plaque and gingivitis scores was greatest among subjects using rinses C and D. Subjects in these 2 groups also had the lowest incidence of plaque and gingivitis scores of 2 + . It is concluded that the effects of sanguinaria rinses on developing plaque and gingivitis are influenced more by sanguinaria concentrations than the presence or absence of zinc ion , but that zinc ion may provide a mild enhancement of sanguinaria effectiveness against gingivitis Forty healthy adult volunteers from the Junior Comprehensive Care Clinics at New York University College of Dentistry were accepted as subjects for this three-month , examiner-blinded , parallel-group clinical trial . To be eligible for a baseline clinical examination , subjects had to first indicate that during the previous six months they habitually brushed their teeth two or more times per day and had noticed " bleeding gums " or " blood in the toothpaste " after brushing or after flossing their teeth . At the baseline examination , subjects were enrolled in the study if they were found to have at least five Löe-Silness gingival bleeding sites and 20 natural teeth , including four molars . Subjects were assigned to one of the two following treatment groups : 1 ) Herbal Mouth and Gum Therapy ; or 2 ) Control ( distilled water and dye ) . Subjects were instructed to clean their teeth in their usual manner , not to use any other mouthrinses or oral irrigation products for the duration of the study . Subjects were to return for clinical examinations after three months of product use . At these examinations , gingivitis and gingival bleeding scores were recorded . An independent t-test before treatment indicated that there were no significant differences between the baseline evaluations of the two groups in the study . A one-way analysis of variance ( ANOVA ) , comparing gingivitis and bleeding scores from baseline and three months with the baseline scores as a covariate , indicated that Herbal Mouth and Gum Therapy produced a statistically significant effect ( p < 0.01 ) on both parameters relative to the control mouthrinse . The results of this study support the clinical efficacy of Herbal Mouth and Gum Therapy in reducing gingivitis and gingival bleeding There is a continuing search for ingredients to enhance the chemical plaque inhibitory action of oral hygiene products . Sanguinarine , other natural extracts and triclosan have already been used in products . The aim of this study was to evaluate a number of triclosan and natural product rinses for effects on plaque regrowth . In particular , the influence of other rinse components were assessed , notably sodium lauryl sulphate ( SLS ) and zinc . The study was a r and omised , blind , 9-cell cross-over design to measure the effects of each rinse on 4-day plaque regrowth from a zero baseline . 15 volunteers rinsed 2x daily with each product and plaque was recorded by area and score . The 0.2 % chlorhexidine rinse ( positive control ) was significantly more effective , and the saline rinse ( negative control ) significantly less effective , than other rinses . Sanguinarine alone was little different from saline and the addition of zinc made a modest improvement in activity . The 3 triclosan/SLS rinses were more effective than the sanguinarine rinses but similar to their minus triclosan control rinse . A natural product/SLS experimental rinse was second to chlorhexidine and , in many analyses , significantly better than all other rinses , but caused some oral erosions . The results indicate that the plaque inhibitory properties of basic ingredients such as SLS may be difficult to enhance or surpass . However , the possible range of recipes , particularly using natural ingredients , provides scope for research and development in the field of oral hygiene products The results of a study to investigate the effectiveness of a propolis-containing mouthrinse in the inhibition of de novo plaque formation are presented . Subjects used a propolis-containing rinse , a negative control and a positive control in a double-blind , parallel , de novo plaque formation study design . The chlorhexidine mouthrinse was significantly better than the others in plaque inhibition . The propolis-containing rinse was marginally better than the negative control , but this difference was not significant This study compared the clinical efficacy of three mouthrinses containing either 0.12 % chlorhexidine , phenolic compounds , or sanguinarine , which were used unsupervised , in a placebo-controlled , double-blind study of 6 months ' duration . The study was conducted according to ADA clinical guidelines for evaluation of antigingivitis agents and was completed by 481 adults . Following baseline exams and a prophylaxis , subjects were r and omly divided into treatment groups matched for age , gender , and gingivitis severity , and were instructed to use the rinses in accordance with manufacturer 's directions . Followup examinations evaluated supragingival plaque , gingivitis , and gingival bleeding . Compared to placebo at 6 months , the group rinsing with 0.12 % chlorhexidine had significantly less gingivitis ( 31 % reduction ) , gingival bleeding ( 39 % reduction ) , and plaque ( 49 % reduction ) and was significantly better than any of the other treatment groups ( P less than 0.05 ) . Both the phenolic and sanguinarine groups showed moderate , yet significant , reductions in plaque compared to placebo ( 24 % and 12 % respectively ) yet were significantly less effective than the 0.12 % chlorhexidine rinse ( P less than 0.05 ) . However , neither the phenolic nor sanguinarine rinses were significantly different than placebo in their effects on gingivitis or gingival bleeding . These results support previous published results on the superiority of 0.12 % chlorhexidine when used in conjunction with professional care and as an adjunct to routine oral hygiene practice The efficacy of combined use of toothpaste and oral rinse containing sanguinaria extract and zinc chloride was compared to placebo products in a 6-month clinical trial . Sixty subjects with moderate levels of plaque and gingivitis were r and omly assigned to active and placebo groups . Noninvasive measures of plaque and gingivitis were assessed at baseline and at 2 , 6 , 8 , 14 , 20 , and 28 weeks . Bleeding on probing was measured at baseline and 6 , 14 , and 28 weeks . Active group scores were significantly lower ( P less than .0001 ) than placebo scores at each post-baseline time point for all indices , with the exception of plaque at 2 weeks . The 28 week active group scores were 21 % lower than the placebo group for plaque , 25 % lower for gingivitis , and 43 % lower for bleeding on probing . No dental staining or taste alteration was reported in the active group . Three of 30 active group subjects exhibited minor soft tissue irritations that resolved spontaneously without discontinuation of product use . Results indicate that the test products showed good levels of safety and efficacy when administered in a combined use regimen for 6 months BACKGROUND Oil pulling has been used extensively as a traditional Indian folk remedy for many years for strengthening teeth , gums , and the jaw and to prevent decay , oral malodor , bleeding gums , dryness of the throat , and cracked lips . AIMS The aim of this study was to evaluate the effect of oil pulling with sesame oil on plaque-induced gingivitis and to compare its efficacy with chlorhexidine mouthwash . MATERIAL S AND METHODS A total of 20 age-matched adolescent boys with plaque-induced gingivitis were selected for this study . They were divided r and omly into the study or oil pulling group ( Group I ) and the control or chlorhexidine group ( Group II ) with 10 subjects in each group . Plaque index and modified gingival index scores were recorded for the 20 subjects and baseline plaque sample s were also collected . The plaque sample s were used to identify the microorganisms and to measure the total colony count of the aerobic microorganisms present . The study group was subjected to oil pulling with sesame oil and the control group was given chlorhexidine mouthwash everyday in the morning before brushing . Re assessment of the index scores and collection of plaque for measuring the colony count of the aerobic microorganisms was done after 10 days . RESULTS There was a statistically significant reduction of the pre- and post-values of the plaque and modified gingival index scores in both the study and control groups ( P < 0.001 in both ) . There was a considerable reduction in the total colony count of aerobic microorganisms present in both the groups . CONCLUSION The oil pulling therapy showed a reduction in the plaque index , modified gingival scores , and total colony count of aerobic microorganisms in the plaque of adolescents with plaque-induced gingivitis A novel mouthrinse ( IND 61,164 ) containing essential oils and extracts from four plant species ( Melaleuca alternifolia , Leptospermum scoparium , Calendula officinalis and Camellia sinensis ) were tested . This study aim ed to evaluate the safety , palatability and preliminary efficacy of the rinse . Fifteen subjects completed the Phase I safety study . Seventeen subjects completed the Phase II r and omized placebo-controlled study . Plaque was collected , gingival and plaque indices were recorded ( baseline , 6 weeks , and 12 weeks ) . The relative abundance of two periodontal pathogens ( Actinobacillus actinomycetemcomitans , Tanerella forsythensis ) was determined utilizing digoxigenin-labeled DNA probes . ANCOVA was used at the p = 0.05 level of significance . Two subjects reported a minor adverse event . One subject withdrew from the study . Several subjects objected to the taste of the test rinse but continued treatment . Differences between gingival index , plaque index or relative abundance of either bacterial species did not reach statistical significance when comparing nine placebo subjects with eight test rinse subjects . Subjects exposed to the test rinse experienced no abnormal oral lesions , altered vital signs , changes in liver , kidney , or bone marrow function . Larger scale studies would be necessary to determine the efficacy and oral health benefits of the test rinse Abstract The aim of this clinical pilot study was to compare the effect of tea tree oil with the effect of water and chlorhexidine on supragingival plaque formation and vitality . Eight subjects were asked to refrain from any kind of mechanical oral hygiene for 4 days after professional tooth cleaning ( day 0 ) , and to rinse with water instead for 1 week , with chlorhexidine in a second and tea tree oil in a third test week . The plaque index ( PI ) , which was evaluated daily ( days 1–4 ) , served as a clinical control parameter . On the last day of the study ( day 4 ) , the plaque covering the front teeth was stained , photographed , and therefrom the plaque area ( PA ; % ) was estimated using a digital measuring system . Each day of the study ( days 1–4 ) , the sample d plaque was examined using a vital fluorescence technique . Tea tree oil reduced neither the clinical parameters ( PI and PA ) nor the vitality of the plaque flora significantly . Within the limitations of the study design , it was determined that a solution with tea tree oil – utilized as ordinary mouthwash – has no positive effect on the quantity or quality of supragingival plaque OBJECTIVES To determine the effects of herbal mouthwash containing the pericarp extract of Carcinia mangostana L on volatile sulfur compound ( VSC ) levels , plaque index ( PI ) and papillary bleeding index ( PBI ) in gingivitis subjects and the recurrence of these parameters after periodontal treatment . METHODS Sixty subjects who were diagnosed as having mild or moderate chronic gingivitis were r and omly distributed into herbal or placebo mouthwash groups . On day 1 , all parameters were recorded . Subjects rinsed with the assigned mouthwash and VSC was measured at 30 min and 3 h post-rinsing . For the following 2 weeks , subjects practice d their usual oral hygiene and rinsed with the assigned mouthwash twice daily after tooth brushing . On day 15 , parameters were recorded . In the 4-week washout period that followed , subjects received scaling and polishing . After another baseline examination , they were re-r and omized into the herbal or placebo group and rinsed with mouthwash for 2 weeks . All parameters were re-evaluated on day 15 . RESULTS All parameters were significantly different compared to baseline in both groups at 30 min , 3 h and day 15 ( p < 0.05 ) . When compared between groups , VSC was significantly different at day 15 ( p < 0.05 ) . After scaling , poloshing and rinsing with mouthwash for 2 weeks , PI and PBI were significantly different compared to baseline ( p < 0.05 ) while VSC was not ( p > 0.05 ) . When compared between groups , VSC was significantly different ( p < 0.05 ) . CONCLUSION Herbal mouthwash containing the pericarp extract of G. mangostana may be used as an adjunct in treating oral malodor A previous clinical screening study demonstrated that a cetylpyridinium chloride ( CPC ) essential oil mouthrinse inhibited plaque regrowth to a significantly greater extent than a negative control or a triclosan/copolymer rinse when used without toothbrushing . The purpose of this study was to evaluate the same ingredient combination as a pre-brushing rinse over a 6-week period . The study employed a 4 group parallel design with a minimum of 50 subjects per group . Subjects with a minimum baseline plaque index of 1.95 were recruited . The formulations employed were two variations of a CPC/essential oil rinse , a triclosan/copolymer product , and a hydroalcohol negative control . Subjects were rendered plaque free at baseline and then rinsed twice daily before toothbrushing with their allocated product . Plaque was scored at 6 days and 6 weeks . Plaque scores were reduced at 6 days compared to baseline but there were no significant differences between any of the groups . At 6 weeks , plaque scores were significantly lower in both CPC/essential oil groups compared to control . Although both CPC/essential oil groups showed plaque scores which were lower than the triclosan group , in only one of the groups was the difference significant . The triclosan product was not significantly different from control . The results support the previous findings that a CPC/essential oil rinse could be a useful adjunct to oral hygiene when used prior to normal toothbrushing An open , r and omized , controlled study with two parallel treatment groups was done to evaluate the efficacy of a Lippia sidoides essential oil ( EO ) 1 % mouthrinse compared with chlorhexidine 0.12 % mouthrinse , applied two times daily for 1 week , in the treatment of dental plaque and gingivitis . Fifty-five patients were included in the study . The efficacy variables were the colony count of Streptococcus mutans from the stimulated saliva and periodontal indices on days 0 , 7 and 30 after commencement of therapy . Twenty eight patients received chlorhexidine mouthrinse ( Periogard((R ) ) ) and 27 Lippia sidoides essential oil mouthrinse ( Cepakill((R ) ) ) . The clinical and microbiological parameters were significantly reduced by both mouthrinses . No significant difference was seen between the two groups ( p > 0.05 ) . There was a significant reduction in the colony count of S. mutans in both groups ( p < 0.05 ) . Chlorhexidine treatment reduced more efficiently than L. sidoides , however , no statistical difference was seen , the efficacy of both groups was similar ( p = 0.3 ) . The results indicate that Chlorhexidine mouthrinse reduced plaque index , gingival bleeding and the number of CFU ( colonies forming units ) more efficiently than L. sidoides but did not reach statistical significance . This study demonstrated that Lippia sidoides EO mouthrinse is effective in reducing microbial plaque and gingival inflammation BACKGROUND The aim of the present study was to investigate the efficacy of an herbal-based mouthrinse in combination with an oral irrigator in reducing gingival inflammation . METHODS A total of 89 patients ( 45 females , 44 males ; mean age 49.1 + /- 1.31 years ) were included in this prospect i ve , r and omized , double-blind clinical study and allocated to 3 treatment groups : group 1 ( n = 34 ) , treated with an oral irrigator with subgingival tips and an herbal-based mouthrinse ; group 2 ( n = 29 ) , the oral irrigator was applied in combination with a conventional mouthwash ; and group 3 ( n = 26 ) , treated with the conventional mouthwash without subgingival irrigation . Data collected at baseline and after 4 , 8 , and 12 weeks included gingival index ( GI ) , sulcus bleeding index ( SBI ) , plaque index ( PI ) , and probing depth ( PD ) . RESULTS Over a period of 3 months , GI decreased from 1.80 + /- 0.04 to 1.56 + /- 0.04 in group 1 ; from 1.79 + /- 0.05 to 1.68 + /- 0.04 in group 2 ; and remained nearly constant in group 3 ( from 1.79 + /- 0.05 to 1.81 + /- 0.04 ) . Differences between the groups were significant ( analysis of variance , P < 0.05 ) . SBI values in group 1 were reduced from 2.51 + /- 0.06 to 2.13 + /- 0.06 after 3 months and were significantly lower than in group 2 ( P = 0.001 ) and 3 ( P = 0.002 ) , with SBIs of 2.44 + /- 0.06 and 2.42 + /- 0.07 , respectively , after 12 weeks . A reduction in PI was noted for all 3 groups throughout the follow-up period , with no statistically significant differences . Probing depths were not reduced significantly in any group . CONCLUSION Subgingival irrigation with an herbal-based mouthrinse led to a significant reduction in both SBI and GI . This regimen can , therefore , be recommended as an adjunctive procedure to reduce gingival inflammation BACKGROUND Brushing and flossing are the most widely accepted procedures , the ' gold st and ard ' , for controlling bacterial plaque , but these mechanical methods have limitations . Based on results derived from several clinical trials , essential oil ( EO ) mouthrinse ( Listerine ( ® ) ) and a chlorhexidine mouthrinse have been accepted by ADA to be used as an adjunct to routine mechanical oral hygiene measures however , both of them are associated with side effects , therefore , the present study was undertaken to evaluate the antiplaque efficacy of a new herbal formulation as compared to an EO and chlorhexidine rinse . MATERIAL S AND METHOD The study was a single blind parallel r and omized controlled trial involving four groups . 48 volunteers refrained from all oral hygiene measures for 4 days , but rinsed instead twice daily with 10 ml of a herbal ( HM ) , EO , chlorhexidine ( CHX ) or a placebo ( PL ) solution . Plaque index and plaque area ( PA ) was assessed on Day 4 . RESULTS The HM and EO showed a significant inhibition of plaque regrowth compared to PL ( P<0.001 ) , but the lowest values of PI and PA were obtained with CHX . Statistically significant difference in plaque parameters was observed when CHX was compared to HM and EO , and HM to EO rinse . CONCLUSION The new herbal mouthrinse had a promising plaque inhibitory potential but it not as efficacious as chlorhexidine in preventing plaque regrowth BACKGROUND Gingivitis is a chronic inflammatory condition , result ing from gingival bacteria and bacterial byproducts . Antiplaque oral rinses reduce inflammation by removing or inhibiting plaque formation . The purpose of this pilot study was to examine the anti-inflammatory effects of HM-302 , a mouth rinse based on natural products , on gingival inflammation . METHODS A prospect i ve , double-blinded , r and omized parallel-group controlled trial involving 62 patients was conducted to assess efficacy and safety . During a 2-week period with no dental hygiene , subjects were r and omized to receive either the study rinse ( HM-302 ) ; a cetylpyridinium chloride ( CPC ) rinse ; an essential oils ( EO ) rinse ; or a water-only preparation . The gingival index ( GI ) , plaque index ( PI ) , and number of bleeding sites were measured at baseline and at the end of the study period . RESULTS Progression of gingival inflammation result ing from lack of dental hygiene was lowest in patients treated with the HM-302 rinse , and was significantly less marked than in patients treated with the water-only preparation . When compared to the CPC and EO treatments , HM-302 was the only mouth rinse that was significantlybetter than the control , with respect to both the change in absolute GI scores ( p = .006 ) and to the percent increase in GI scores ( p = .012 ) . No serious adverse effects were noted in any of the study groups . CONCLUSION HM-302 is a safe and effective treatment for preventing the development of gingival inflammation in an experimental gingivitis model . Further research is needed to evaluate its long-term effects The effects on developing plaque and gingivitis following rinsing with a placebo oral rinse or an oral rinse containing 300 micrograms/ml sanguinaria extract ( sanguinaria ) were compared to effects produced by supragingival irrigation with dilute solutions of the rinse corresponding to 22.5 micrograms/ml sanguinaria and 90 micrograms/ml sanguinaria . The study design was a repeated measures , single-blind crossover with no oral hygiene over 2 weeks duration . After 7 and 14 [ corrected ] days , significantly lower plaque and gingivitis scores were obtained with use of the sanguinaria-containing rinse and irrigating solutions compared with the placebo rinse . There were no significant differences in plaque and gingivitis scores between the groups using the sanguinaria rinse and the sanguinaria irrigating solutions . A comparison [ corrected ] of % distribution of 0 , 1 and 2 + scores also indicated that rinsing and supragingival irrigation with sanguinaria was more effective in plaque and gingivitis control than rinsing with the placebo . The results suggest that sanguinaria oral rinse may be effective in controlling plaque and gingivitis when delivered by manual rinsing or supragingival irrigation The aim of this double blind study was to evaluate the effect of various mouthwashes : Chlorhexidine , Essential oil , Azadirachta indica ( Neem ) extract , and Povidone iodine on gingival tissue interleukin-2 ( IL-2 ) and interferon-gamma ( IFN-gamma ) levels in patients with chronic gingivitis . A total of 8O patients ( 42 boys , 38 girls ; mean age 16.0 + /- 1.8 years ) were included in this study . Patients were r and omly assigned into four groups of 20 each : Group I -- Azadirachta indica ( Neem ) extract , Group II -- Essential oil , Group III -- Povidone iodine , and Group IV -- Chlorhexidine . They were instructed to use these mouthwashes for two weeks . Plaque and gingival indices scores , and IL-2 and IFN-gamma levels in the gingival tissues were measured at baseline and after two weeks of mouthwash use . Results showed the reduction of plaque and gingival indices , and IL-2 and IFN-gamma level with Chlorhexidine , Essential oil , and Povidone iodine , which were found to be statistically significant . Although Neem reduced the level of plaque and gingival indices , and IL-2 and IFN-gamma to a certain level , it was not statistically significant . Therefore , Chlorhexidine , Essential oil , and Povidone iodine mouthwashes can be used as an adjunct to oral prophylaxis in reducing pro-inflammatory cytokines , IL-2 and IFN-gamma in patients with chronic gingivitis The aim of the study was to evaluate the efficacy of Parodontax ® ( GlaxoSmith-Kline , Bühl , Germany ) on the signs gingival inflammation and the enzyme activity of matrix metalloproteinase-8 ( aMMP-8 ) in the gingival crevicular fluid . After approval by the ethics commission , a total of 50 volunteers participated in the study ; group 1 ( n = 25 , age : 43 ± 12 years ) with moderate gingivitis ( BOP + ) and group 2 ( n = 25 , age : 29 ± 11 years ) with clinical ly healthy gingival conditions ( BOP - ) . After obtaining anamnestic data , the dental examination included assessment of oral hygiene ( Quigley & Hein 1962 ) , gingival inflammation ( Saxer & Mühlemann 1975 ) , probing pocket depth and clinical attachment level . Gingival crevicular fluid was collected from both groups . A quantitative assessment of aMMP-8 in the gingival crevicular fluid sample s was performed ( DentoAnalyzer , Dentognostics GmbH , Jena , Germany ) . Study participants were instructed to use only Parodontax ® . After three weeks , all parameters were measured again . The aMMP-8 values of group 1 were significantly reduced after the use of Parodontax ® toothpaste and mouthwash ( p < 0.001 ; baseline median 41.25 ± 38.16 ng/ml , final post-treatment median 7.73 ± 7.58 ng/ml aMMP-8 eluate ; group 2 : baseline median 3.75 ± 3.16 ng/ml , final post-treatment median 3.73 ± 1.54 ng/ml aMMP-8 eluate ) . Gingival inflammation and plaque accumulation were reduced . It was shown that Parodontax ® was effective in reducing the enzymatic activity of inflammation Background : This study was carried out to investigate the effectiveness of a propolis-containing mouthrinse in inhibition of plaque formation and improvement of gingival health . Material s and Methods : Thirty subjects were selected and r and omly assigned into three groups of ten subjects each , which received a propolis-containing mouthrinse , or a negative control ( Saline ) or a positive control ( Chlorhexidine 0.2 % ) . Plaque index and gingival index were assessed at baseline and at a five-day interval . Results : Chlorhexidine mouthwash was found to be better than propolis and saline in inhibiting plaque formation . Propolis was found to be only marginally better than chlorhexidine in improving gingival scores . Conclusion : The present study suggests that propolis might be used as a natural mouthwash , an alternative to chemical mouthwashes , e.g. , chlorhexidine . Further , long term trials are required for more accurate data and any conclusive evidence Cacao bean husk extract ( CBH ) has been shown to possess antibacterial and antiglucosyltransferase activities through its unsaturated fatty acids and epicatechin polymers , respectively . In the present study , the antiplaque activities of CBH were examined in vitro and in vivo . The extract inhibited the adherence of Streptococcus mutans MT8148 to saliva-coated hydroxyapatite and reduced the accumulation of artificial dental plaque by S. mutans MT8148 on orthodontic wire . The number of mutans streptococci in dental plaque was also significantly reduced when human dental plaque was exposed to CBH from 21 children at 37 degrees C for 1 h. For the in vivo study , 28 volunteers aged 19 - 29 yr old rinsed their mouth with CBH , before and after each intake of food and before sleeping at night for 4 d without using other oral hygiene procedures . Plaque depositions and the numbers of mutans streptococci were reduced in the subjects , compared with rinsing with 1 % ethanol alone . These results indicate that CBH possesses significant antiplaque activity in vitro and in vivo The effectiveness of a mouthwash based on triclosan in combatting plaque and gingivitis was compared with a mouthwash based on nonsaponifiable maize germ ( Zea mays L ) . Both were used to supplement conventional mechanical oral hygiene . The study was carried out under double-blind conditions with a negative control ( a placebo ) and a positive control ( a mouthwash based on chlorhexidine ) . After a period of 14 days to allow the Plaque Index and Gingival Index to st and ardize , the 43 subjects who formed the sample were examined weekly for 3 weeks . During the study , five subjects were excluded because they did not meet the criteria for selection for the study . Although the mouthwash based on triclosan reduced the Plaque Index by 7.3 % in comparison with the placebo negative control ( a less marked effect than that of chlorhexidine , which achieved an 8.43 % reduction ) , it had scarcely any effect on the Gingival Index . The mouthwash based on Zea mays L had no beneficial action on the Plaque Index , which increased slightly , but it led to an improvement in the Gingival Index ( 7.17 % in comparison with the placebo ) Although the experimental gingivitis model has been used extensively since 1965 , some doubts exist concerning the nature of the tissue response in this model . Accordingly , the present study was design ed to determine whether or not experimental gingivitis responded to 0.1 % folate mouthwash ( MW ) in a similar manner to that already reported for established gingivitis . 20 male dental students took part in a double blind cross-over study which involved two 3-week experimental periods with r and om allocation to folate or placebo MW . The experimental site was the lower anterior area and 24 points of gingival examination were made at baseline and weeks 1 , 2 and 3 . Inflammation was assessed by presence or absence of colour change , and bleeding being slight , profuse or absent when gingivae were stroked with a blunt probe . A plaque sample was evaluated using dark field microscopy , and dry weight of accumulated plaque was measured at the end of each experimental period . Folate MW did not appear to have any statistically significant effects on accumulated plaque , or clinical signs of experimental gingivitis in this study . The different response of experimental gingivitis to folate MW , compared with the response of established gingivitis already reported , further suggests that experimental gingivitis may not represent an authentic replica of the cellular and immunological responses occurring in established gingivitis OBJECTIVES To study the effect of mouthrinses with salivary replacement substances on oral conditions in patients with primary Sjögren 's syndrome . DESIGN Cross-over , double-blind study . SETTING Facilities at the Centre for Oral Health Sciences , Malmö University and at Malmö University Hospital , Malmö , Sweden . SUBJECTS Twenty-two patients with Sjogren 's syndrome . INTERVENTION Linseed extract Salinum alone ( Sal ) or with addition of chlorhexidine ( Sal/Chx ) was used for mouthrinsing during 3-week periods of rinsings separated by a 3-week " wash-out " period . MEASUREMENTS Recordings of percentages of sites with dental plaque and bleeding on probing , mirror friction test and microbiological analyses . Question naire on oral symptoms due to reduced salivation . RESULTS Dental plaque and bleeding on probing were reduced after Sal and after Sal/Chx . Friction was reduced after both treatments . No significant differences for counts of studied microbial groups were seen after Sal but the total anaerobically cultured microorganisms and of mutans streptococci fell after Sal/Chx ( p<0.05 and p<0.001 ) . Symptoms of oral dryness improved following Sal and Sal/Chx ( p<0.05 and p<0.001 respectively ) . Speaking problems and burning mouth symptoms improved after use of Sal ( p<0.05 ) . CONCLUSIONS Positive effects on symptoms in patients with Sjögren 's syndrome were seen after use of Salinum without or with chlorhexidine The aim of the study was to compare the anti-plaque effect of sanguinaria extract to that of a known effective agent , chlorhexidine gluconate , and to that of a known ineffective agent , tap water . The study was conducted as a 3 times crossed-over and blindly evaluated 3 week clinical trial . 12 dental students rinsed in an individually r and omized sequence twice daily for 4 days ( Monday to Friday ) with Viadent containing 0.03 % sanguinaria extract ( 0.01 % sanguinarine chloride ) and a 1000 ppm concentration of zinc ions ( ZnCl2 ) , 2 X 30 s X 10 ml ; with Hibitane Dental containing 0.2 % chlorhexidine gluconate , 1 min X 10 ml ; and with tap water , 1 min X 10 ml . Mechanical oral hygiene was allowed only during the 3 days between test periods . When measured according to the plaque index or in terms of plaque wet weight , only the chlorhexidine rinse further reduced the low Monday scores . No significant difference was observed between Friday scores after rinses with Viadent and water . The variation in effect of the 3 rinses was less marked when assessed by means of area of plaque on the tooth surfaces . Subjectively , both the taste and effect of Viadent was reported to be poor . In a second controlled clinical trial using the same design , no significant difference in anti-plaque effect was found between the commercially available Viadent rinse and an experimental rinse with a tripled concentration of sanguinarine chloride but the same content of zinc BACKGROUND Chlorhexidine ( CHX ) rinsing after periodontal surgery is common . We assessed the clinical and microbiological effects of two CHX concentrations following periodontal surgery . MATERIAL S AND METHODS In a r and omized , controlled clinical trial , 45 subjects were assigned to 4 weeks rinsing with a 0.05 CHX/herbal extract combination ( test ) or a 0.1 % CHX solution . Clinical and staining effects were studied . Subgingival bacteria were assessed using the DNA-DNA checkerboard . Statistics included parametric and non-parametric tests ( p<0001 to declare significance at 80 % power ) . RESULTS At weeks 4 and 12 , more staining was found in the control group ( p<0.05 and p<0.001 , respectively ) . A higher risk for staining was found in the control group ( crude OR : 2.3:1 , 95 % CI : 1.3 to 4.4 , p<0.01 ) . The absolute staining reduction in the test group was 21.1 % ( 9 5 % CI : 9.4 - 32.8 % ) . Probing pocket depth ( PPD ) decreases were significant ( p<0.001 ) in both groups and similar ( p=0.92 ) . No rinse group differences in changes of bacterial counts for any species were found between baseline and week 12 . CONCLUSIONS The test CHX rinse result ed in less tooth staining . At the study endpoint , similar and high counts of periodontal pathogens were found A former double-blind study evaluated the effect of a 14-day period of systemic and topical folate supplementation on gingival inflammation during pregnancy ( Pack & Thomson 1980 ) . The current experiment was similar to the earlier one except that supplementation was for 28 days during the eighth month only . Thirty women during their 32nd week of pregnancy were r and omly divided into three equal groups . Control Group A received placebo mouthwash ( MW ) and placebo tablets ; Group B received placebo MW and one 5 mg folate tablet daily ; Group C received placebo tablets and rinsed with folate MW twice daily for 1 min . At the beginning and end of the experimental period , oral status was determined using a plaque index ( PlI ) and a gingival index ( GI ) . Each subject furnished a 1-week diet record which was analysed for dietary folate . No differences in parameters existed between groups at the commencement of the study except for folate levels which were lower in Group B. Results confirmed the findings of the former experiment . Group C showed highly significant improvement in GI despite no significant changes in PlI ( 0.001 less than P less than 0.01 ) , whilst in Group B , changes in gingival health were not statistically significant ( 0.05 less than P less than 0.10 ) . No significant changes were demonstrated in Group A. Folate levels increased significantly in Groups B and C. Dietary folate was similar in all groups A sanguinaria-containing toothpaste and oral rinse regimen was evaluated during a 6-month period to determine its effectiveness in controlling plaque , gingival inflammation , and sulcular bleeding . Oral hygiene instructions and a 1-month pre study brushing period failed to produce a significant improvement in health among the 24 subjects as determined by the three evaluation parameters . After the oral hygiene period , the subjects were r and omly assigned to the active treatment ( marketed Viadent toothpaste and oral rinse ) or the placebo treatment ( same base formulas without sanguinaria ) . Treatments were evaluated using the Löe and Silness gingival index , the Silness and Löe plaque index , and the Mühlemann and Son sulcular bleeding index at baseline and monthly through 6 months . The sanguinaria regimen reduced plaque by 57 % , gingival inflammation by 60 % , and sulcular bleeding by 45 % from baseline compared with placebo group reductions of 27 % ( plaque ) and 21 % ( gingival inflammation ) , and an increase of 30 % in bleeding index . Repeated- measures analysis of covariance with baseline scores used as covariates showed statistically significant differences at 6 months for plaque ( active 0.39 ; placebo 0.68 , p less than 0.01 ) , gingival inflammation ( active 0.32 ; placebo 0.76 , p less than 0.001 ) , and sulcular bleeding ( active 0.34 ; placebo 0.70 , p less than 0.002 ) . Results of this study demonstrated that the combined use of the sanguinaria-containing toothpaste and oral rinse controls and reduces plaque and gingival inflammation in an orthodontic population The popularity and availability of chewing sticks ( Salvadora persica ) in the Asia , Middle East and Africa make them a commonly used oral hygiene tool in those societies . Salvador persica chewing stick called miswak is frequently used in Saudi Arabia . The antimicrobial effects of miswak has been well documented . The aim of this study is to find our the effect of aqueous extracts of miswak on healthy and periodontally involved human dentine with Scanning Electron Microscopy ( SEM ) in vitro . 25 % aqueous extract of freshly prepared miswak solution was used for the study . Twelve human premolars teeth ( 6 healthy and 6 with periodontal disease ) recently extracted for orthodontic and periodontal reasons were used . 24 SEM specimens were prepared and treated with miswak extract with different conditions e.g. soaking and burnishing with miswak extract . Soaking the healthy and periodontally diseased root dentine in miswak extract result ed in partial removal of smear layer and occlusion of dentinal tubules was observed in dentine specimens burnished with miswak solution . Further research is needed to evaluate the effect of aqueous extract of miswak on etched human dentine at higher concentrations Bacterial growth of a vegetable oil-based product was determined in vitro . Growth of Streptococcus mutans and Veillonella alcalescens was strongly inhibited for dilutions up to 50x . On the basis of these results , it was decided to evaluate the short-term , clinical efficacy of a 1:10 dilution of the concentrated product in water . Fifteen human volunteers employed this rinse twice-a-day during a six-day period . Planimetric plaque scores , as well as the plaque and gingival indexes according to Löe , were assessed at the beginning and end of this period . The efficacy of such a rinse , though less than of chlorhexidine-based products , turned out comparable to several other commercially available products with a reasonable potential in maintaining a low gingival index The aim of this study was to evaluate the effect of a mouthrinse containing propolis SNB-RS on 3-day dental plaque accumulation . Six volunteers took part in a double-blind crossover study performed in two phases of 3 days . During each phase the volunteers refrained from all oral hygiene and rinsed with 20 % sucrose solution 5 times a day to enhance dental plaque formation and with mouthrinse ( placebo or experimental ) twice a day . On the 4th day , the plaque index ( PI ) of the volunteers was scored and the supragingival dental plaque was analyzed for insoluble polysaccharide ( IP ) . The PI ( SD ) for the experimental group was 0.78 ( 0.17 ) , significantly less than for the placebo group , 1.41 ( 0.14 ) . The experimental mouthrinse reduced the IP concentration in dental plaque by 61.7 % compared to placebo ( p < 0.05 ) . An experimental mouthrinse containing propolis SNB-RS was thus efficient in reducing supragingival plaque formation and IP formation under conditions of high plaque accumulation This clinical investigation examined the effect of a sanguinarine extract on bacterial plaque growth in man . Three different mouthrinses were examined : ( i ) Veadent containing 0.03 % sanguinarine and 0.2 % zinc chloride ( test rinse ) ; ( ii ) a vehicle solution containing all the excipients of Veadent except the 0.03 % sanguinarine ( control rinse ) ; ( iii ) Hibident a 0.2 % chlorhexidine digluconate formulation ( positive control rinse ) . The trial in which 12 dental students participated , was design ed as a single-blind , cross-over study . During 3 experimental periods of 18 days , the participants refrained from mechanical oral hygiene and rinsed twice a day with one of the above mentioned solutions . Between experimental phases , a wash-out period of 11 days was instituted . In each subject , 4 teeth were r and omly selected for assessment . Clinical evaluations were performed at days 1 ( 0 , 4 , 8 , 12 hours ) , 2 , 4 , 11 and 18 . The plaque on the buccal surfaces of the selected teeth was disclosed with neutral red 0.05 % and colour slides taken . The % of the tooth surface covered with plaque was calculated planimetrically from these colour slides . The present results show an excellent anti-plaque effect with Hibident , a very small effect with Veadent and a negligible effect with the vehicle solution without the sanguinarine . These findings would suggest that the Veadent mouthrinse would have at most only a limited role as a plaque inhibitor |
10,375 | 21,238,790 | No significant difference was observed in the healing rate between single- versus multiple-visit root canal treatment , as well as the incidence of medium-term post-obturation pain .
On the basis of current studies , the healing rate of single- and multiple-visit root canal treatment is similar for infected teeth .
Patients experience less frequency of short-term post-obturation pain after single-visit than those having multiple-visit root canal treatment | INTRODUCTION The choice of single- versus multiple-visit root canal treatment for infected teeth is in dispute .
The purpose of this systematic review was to compare the healing rate and post-obturation pain of single- versus multiple-visit root canal treatment for teeth with infected root canals . | AIM The purpose of the present study is to evaluate the healing of periapical lesions of teeth with positive and negative canal cultures at the time of obturation , and to evaluate the periapical healing of teeth treated in one visit ( without ) or in two visits with an interappointment dressing of calcium hydroxide . METHODOLOGY Thirty-nine patients received root-canal treatment . In the first visit , teeth were instrumented , and 18 of these teeth were filled ( after microbiological sampling ) with calcium hydroxide in sterile saline . The other 21 teeth were obturated with gutta-percha and AH-26 sealer after microbiological sampling . Four weeks later , the teeth with calcium hydroxide were accessed again and after microbiological sampling they were obturated with gutta-percha and AH-26 sealer . Healing of periapical radiolucency was recorded over a period up to 4.5 years . RESULTS In both the treatment groups , the size of the periapical lesions reduced significantly during the follow-up period . Complete radiographic healing was observed in 81 % of the cases in the one-visit group , and in 71 % of the cases in the two-visit group . The probability of success increased continuously over time for both treatment groups . Seven out of eight cases ( 87.5 % ) that showed a positive root-canal culture at the time of obturation healed . The number of colony forming units ( CFU ) in six out of eight positive canals was < 10(2 ) CFU mL(-1 ) . CONCLUSIONS Within the limitations of this study , no significant differences in healing of periapical radiolucency was observed between teeth that were treated in one visit ( without ) and two visits with inclusion of calcium hydroxide for 4 weeks . The presence of a positive bacterial culture ( CFU<10(2 ) ) at the time of filling did not influence the outcome of treatment OBJECTIVES This prospect i ve study was conducted to determine whether there is any significant difference in the incidence of postobturation pain after single- and multiple-visit root canal treatment ( RCT ) . METHODS The frequency of postobturation pain was recorded and evaluated over an observation period of 30 days in 291 of 300 consecutive patients receiving RCT . The patients were assigned r and omly and consecutively into either single- or multiple-visit groups . The canals of all teeth were prepared and filled by a single operator using the step-back and lateral condensation techniques . The data were analysed statistically to determine the relationship , if any , between the pain experienced and pulpal vitality , tooth type , pre-operative pain , and the sex and age of the patient . RESULTS Nine of the 300 patients were excluded from the analysis as they failed to attend for postoperative review s. A significantly higher incidence ( P < 0.01 ) of postobturation pain was found in the multiple-visit group ( 38 % ) than in the single-visit group ( 27 % ) within 24 h of obturation . The incidence of pain decreased thereafter , with all patients being sysmptom free at the end of the observation period . No significant correlation was found between postobturation pain and any other factor , with the exception that teeth which had nonvital pulp prior to treatment were associated with a significantly greater ( P < 0.005 ) incidence of postobutration pain . CONCLUSIONS Pain was significantly higher in the multiple-visit RCT group and significantly associated with the treatment of the nonvital pulp OBJECTIVES This prospect i ve study evaluated the frequency and intensity of postobturation pain and associated factors in adolescents undergoing one- and two-visit root canal treatment . METHODS 121 patients aged 11 - 18 years presenting with molars with pulp necrosis were assigned r and omly into two treatment groups : one- and two-visit ( including interappointment dressing with calcium hydroxide paste ) . The canals of all teeth were prepared using a preflaring ( 2/3 middle-cervical ) and step-back ( 1/3 apical ) preparation techniques and filled with laterally compacted gutta-percha and sealer . Postobturation pain was recorded on a visual analogue scale ( VAS ) of 0 - 5 . Data were statistically analyzed using multivariate logistic regression . RESULTS The frequencies of postobturation pain were 10.5 % ( 6/57 ) in the one-visit group and 23.0 % ( 14/61 ) in the two-visit group . There were no statistically significant differences between the groups ( p=0.07 ) . The intensity of the pain was similar in both groups , particularly flare-ups , with a prevalence of 1.75 % in the one-visit group and 1.65 % in the two-visit group . Postobturation pain was significantly associated with the presence of preoperative pain ( p=0.04 ; OR=3.54 ; CI 95%=1.02 - 12.30 ) and a positive culture at the time of obturation ( p=0.00 ; OR=9.43 ; CI 95%=2.93 - 30.35 ) . CONCLUSIONS Postobturation pain was more present in the two-visit group , but was not statistically significant . The intensity of postobturation pain was similar . Effective microbiological control and the presence of preoperative pain may influence the postobturation pain in adolescents Acute pain and swelling following endodontic treatment are a challenge for both the patient and the dentist . According to previous studies , the incidence of flare-ups increases after endodontic treatment of teeth with necrotic pulps . Calcium hydroxide is currently used as a multi- purpose drug in root canal therapy . The aim of this study was to evaluate the incidence and severity of flare-ups after treatment of pulpless teeth using calcium hydroxide as an intracanal dressing . Sixty patients with single-root necrotic teeth participated in this study . These patients were r and omly divided into three groups of 20 . The patients were treated in Group A in a single-visit approach , in group B with a two-visit approach without any intracanal dressing and group C with a two-visit approach using calcium hydroxide as an intracanal dressing for one week . All of the patients were followed for 72 hours after each treatment session . The information about the incidence and severity of pain and swelling was recorded in tables , using a modified Visual Analogue Scale for pain severity measurement and a scale with four degrees for measuring the severity of swelling . The data were analyzed by chi-square test and GENMODE procedure The choice of one-visit versus two-visit root canal therapy for necrotic teeth with apical periodontitis is a source of current debate . The primary objective of this r and omized controlled clinical trial was to compare radiographic evidence of periapical healing after root canal therapy completed in one visit or two visits with an interim calcium hydroxide/chlorhexidine paste dressing . Ninety-seven patients met the inclusion criteria and consented to participate in this study . Patients were r and omly assigned to either the one-visit or two-visit group , and root canal therapy was performed with a st and ardized protocol . Patients in the two-visit group received an intracanal dressing of calcium hydroxide/chlorhexidine paste . Sixty-three patients , 33 in the one-visit group and 30 in the two-visit group , were evaluated at 12 months . The primary outcome measure was change in apical bone density by using the periapical index ( PAI ) . Secondary outcome measures were proportion of teeth healed or improved in each group . Both groups exhibited equally favorable periapical healing at 12 months , with no statistically significant differences between groups The purpose of this study was to compare intracanal bacterial reduction on teeth instrumented with 0.04 tapered nickel-titanium ( NiTi ) rotary instrumentation to bacterial reduction when using a stainless-steel K-file step-back technique using sterile saline irrigation . Forty-eight patients with apical periodontitis were r and omly assigned treatment type . The canals were sample d before , during , and after instrumentation . The sample s were incubated anaerobically for 7 days at 37 degrees C , colony-forming unit numbers calculated , and a log transformation performed to normalize the counts . Teeth exhibiting apical periodontitis were uniformly infected , whereas vital control teeth were not . A similar and uniform reduction occurred with progressive filing , regardless of technique ( p < 0.0001 ) . There was no detectable difference in colony-forming unit count after NiTi rotary or stainless-steel h and instrumentation ( p = 0.42 ) . Neither technique could predictably render canals free of bacteria . The results of this study indicate NiTi rotary and stainless-steel h and K-file step-back instrumentation techniques were not significantly different in their ability to reduce intracanal bacteria The objective was to evaluate the clinical efficacy of chemomechanical preparation of the root canals with sodium hypochlorite and interappointment medication with calcium hydroxide in the control of root canal infection and healing of periapical lesions . Fifty teeth diagnosed with chronic apical periodontitis were r and omly allocated to one of three treatments : Single visit ( SV group , n = 20 ) , calcium hydroxide for one week ( CH group n = 18 ) , or leaving the canal empty but sealed for one week ( EC group , n = 12 ) . Microbiological sample s were taken to monitor the infection during treatment . Periapical healing was controlled radiographically following the change in the periapical index at 52 wk and analyzed using one-way ANOVA . All cases showed microbiological growth in the beginning of the treatment . After mechanical preparation and irrigation with sodium hypochlorite in the first appointment , 20 to 33 % of the cases showed growth . At the second appointment 33 % of the cases in the CH group revealed bacteria , whereas the EC group showed remarkably more culture positive cases ( 67 % ) . Sodium hypochlorite was effective also at the second appointment and only two teeth remained culture positive . Only minor differences in periapical healing were observed between the treatment groups . However , bacterial growth at the second appointment had a significant negative impact on healing of the periapical lesion ( p < 0.01 ) . The present study indicates good clinical efficacy of sodium hypochlorite irrigation in the control of root canal infection . Calcium hydroxide dressing between the appointments did not show the expected effect in disinfection the root canal system and treatment outcome , indicating the need to develop more efficient inter-appointment dressings The antimicrobial efficacy of endodontic procedures performed in one-visit ( including a 10-min intraappointment dressing with 5 % iodine-potassium-iodide ) was compared with a two-visit procedure ( including an interappointment dressing with calcium-hydroxide paste ) . Teeth with apical periodontitis ( n = 96 ) were r and omly assigned to either group . Root canal sampling and culturing were performed before and immediately after instrumentation , and after medication . Initial sampling demonstrated the presence of microorganisms in 98 % of the teeth . Postinstrumentation sampling showed reduction of cultivable microbiota . Antibacterial dressing further reduced the number of teeth with surviving microbes . In the postmedication sample s , residual microorganisms were recovered in 29 % of the one-visit teeth and in 36 % of the two-visit treated teeth . No statistically significant differences between the groups were discerned . It was concluded that from a microbiological point of view , treatment of teeth with apical periodontitis performed in two appointments was not more effective than the investigated one-visit procedure AIM This prospect i ve clinical study explored the influence of calcium hydroxide as an interappointment dressing on the healing of periapical lesions associated with pulpless teeth that had not been endodontically treated previously . This was achieved by comparing the prognosis after a two-visit root canal treatment with that following a one-visit treatment . METHODOLOGY Seventy-three patients were recruited having one tooth with an endodontically induced lesion . Of these patients , 67 could be re-examined . Calcium hydroxide was placed in the instrumented root canals of 31 teeth for at least one week and the treatment finished at the second visit . Thirty-six teeth were root canal treated at one visit . The criteria for success were the absence of signs and symptoms indicating an acute phase of periapical periodontitis and radiographically a periodontal ligament space of normal width . Methods for event time analysis were used to evaluate and compare the prognosis of both treatment approaches . RESULTS The probability that complete periapical healing will take place increased continuously with the length of the observation period . In both treatment groups the likelihood that the root canal treatment yields a success within an observation time of five years exceeded 90 % . A statistically significant difference between the two treatment groups could not be detected . CONCLUSIONS From a microbiological perspective , one-visit root canal treatment created favourable environmental conditions for periapical repair similar to the two-visit therapy when calcium hydroxide was used as antimicrobial dressing . One-visit root canal treatment is an acceptable alternative to two-visit treatment for pulpless teeth associated with an endodontically induced lesion OBJECTIVE The purpose of this clinical study was to determine the effect of 1- or 2-visit root canal treatment on the postoperative pain in the retreatment cases . STUDY DESIGN Two hundred eighteen cases that required retreatment were included in the study . Obturated and unfilled canal space and the status of periapical tissues were evaluated according to the PAI index . The patients were subcategorized in regard to the presence or the absence of preoperative pain . Approximately half of each category was treated in 1 appointment . After removing the previous root canal obturation material s and biomechanic preparation of root canals , the teeth in the 1-visit group were obturated at the first appointment by using AH 26 sealer and laterally compacted gutta-percha , and those in the 2-visit group were medicated with calcium hydroxide-chlorhexidine combination and then closed with a temporary filling material . One week after the initial appointment , patients were asked about the occurrence of postoperative pain . The level of discomfort was rated as no pain , mild pain , moderate pain , or severe pain ( flare-up ) . Data were statistically analyzed using the chi-squared and Fischer exact tests . RESULTS Eight patients from the 1-visit group and 2 patients from the 2-visit group had flare-ups . There was a statistical difference between the groups ( P < .05 ) . Two-visit root canal treatment was more effective in completely eliminating pain than 1-visit treatment of previously symptomatic teeth ( P < .05 ) . CONCLUSIONS Two-visit endodontic treatment with intracanal medication was found to be effective in reducing postoperative pain of previously symptomatic teeth and decreased the number of flare-ups in all retreatment cases AIM The aim of this study was to evaluate the fate of microorganisms in root canals of teeth with infected pulps and periapical bone lesions with and without the use of calcium hydroxide medication . METHODOLOGY Endodontic sample s were cultured and microorganisms were counted and identified in 43 teeth before ( sample 1 ) and after ( sample 2 ) treatment during the first visit and before ( sample 3 ) and after ( sample 4 ) treatment during the second visit . In the first visit teeth were instrumented and half of the teeth were filled with a thick slurry of calcium hydroxide in sterile saline . The other teeth were obturated with gutta-percha and AH-2 6 sealer . After 4 weeks the teeth with calcium-hydroxide were accessed again and after microbiological sampling they were obturated with gutta-percha and AH-26 sealer . RESULTS The mean total colony forming unit ( CFU ) counts of positive sample s dropped significantly as a result of canal preparation during the first visit from 1.0 x 10(6 ) to 1.8 x 10(3 ) ( between sample s 1 and 2 ) but increased to 9.3 x 10(3 ) in the period between the two visits ( sample 2 and 3 ) . There was no difference in mean total CFU counts of positive sample s between the end of the first ( sample 2 ) and the end of the second visit ( sample 4 ) . The most frequently isolated species were Prevotella intermedia , Capnocytophaga spp .. Actinomyces odontolyticus . Propionibacterium acnes and Peptostreptococcus micros . CONCLUSIONS Although a calcium hydroxide paste was placed in the prepared canals , the number of positive canals had increased in the period between visits . However , the number of microorganisms had only increased to 0.93 % of the original number of CFU ( sample 1 ) . It is concluded that a calcium hydroxide and sterile saline slurry limits but does not totally prevent regrowth of endodontic bacteria The purpose of this prospect i ve study was to evaluate the incidence of postoperative pain after intracanal procedures based on an antimicrobial strategy . Data were examined from 627 teeth that had necrotic pulps or required retreatment . Information was obtained for each patient treated with regard to presence of preoperative pain . Occurrence of periradicular bone destruction detected by radiographs was also recorded . The operators consisted of undergraduate students , who were in their first year of clinical training . Root canals were instrumented and then medicated with a calcium hydroxide/camphorated paramonochlorophenol paste . No systemic medication was prescribed . Approximately 1 week after the initial appointment , patients were asked about the occurrence of postoperative pain and the level of discomfort was rated as no pain , mild pain , moderate pain , or severe pain . Data were statistically analyzed using the Chi-square test . Mild pain occurred in 10 % of the cases , moderate in 3.3 % , and severe ( flare-up ) in 1.9 % . Postoperative pain was significantly associated with the treatment of previously symptomatic teeth without periradicular lesions ( p < 0.01 ) . No other correlations were detected between the occurrence of postoperative discomfort and other clinical conditions . There was also no difference regarding the incidence of postoperative pain between treatment and retreatment ( p > 0.01 ) . The intracanal procedures used in this study to control root canal infections showed a small incidence of postoperative pain , particularly flare-ups , even performed by inexperienced undergraduate dental students OBJECTIVES This prospect i ve study was conducted to determine the flare up rate related to root canal treatment of asymptomatic non vital maxillary central incisor teeth performed in one and two appointments and the relationship , if any between pain and number of treatment visits . METHODS The frequency of postobturation pain and swelling was recorded and evaluated over an observation period of 1 week in a 120 consecutive patients undergoing root canal treatment . The patients were assigned r and omly into one of two groups of 60 patients each . The canals of all teeth were prepared and filled using the step-back preparation and lateral condensation filling techniques . The data were analyzed statistically using Mann-Whitney test . RESULTS Eight of the 120 patients were excluded from the analysis as they failed to attend for postoperative review s. Out of the 112 patients involved in the study 90 patients had no pain , 9 patients had slight pain , 8 patients had moderate pain , and 5 patients had severe pain after 2 days . After 7 days 104 patients had no pain , 4 patients had slight pain , 3 patients had moderate pain and 1 patient had severe pain . CONCLUSIONS No statistically significant difference in the incidence and degree of postoperative pain was found between one and two visit Endodontic procedures . The rate of post obturation flare up in asymptomatic Endodontically treated non vital maxillary centarl incisors was 11.6 and 3.6 % after 2 and 7 days , respectively AIM To assess the treatment results up to 1 year after endodontic treatment of apical periodontitis using a silicone-based sealer in comparison with Grossman 's sealer , and to compare the results at 3 months after treatment with the 12-month follow-up to assess the prognostic value of a 3-month control . METHODOLOGY A total of 199 teeth were treated at three centres . The sealer was r and omly chosen at the time of filling . Treatment results were evaluated clinical ly and radiographically 3 and 12 months after root-canal filling . The periapical status was evaluated using the periapical index ( PAI ) . RESULTS AND CONCLUSIONS Average PAI scores decreased from 3.43 at start to 2.21 at 12 months for Grossman 's sealer and from 3.40 to 2.26 for the silicon-based material . No significant difference between the groups at start or any of the follow ups was seen . The 3-month control was adequate in establishing significant healing in both groups . The improvement of the periapical condition continued at the 12-month examination The purpose of this prospect i ve study was to assess the incidence of flare-ups ( a severe problem requiring an unscheduled visit and treatment ) among patients who received endodontic treatment by the two authors in their respective practice s during a period of one year , and also to examine the correlation with pre-operative and operative variables . The results showed an incidence of 1.58 % for flare-ups from 1012 endodontically treated teeth . Statistical analysis using the chi-square test ( P<0.05 ) indicated that flare-ups were found to be positively correlated with multiple appointments , retreatment cases , periradicular pain prior to treatment , presence of radiolucent lesions , and patients taking analgesic or anti-inflammatory drugs . In contrast , there was no correlation between flare-up , and age , sex , different arch/tooth groups and the status of the pulp This study was performed to evaluate radiographic healing of teeth with apical periodontitis , treated in one visit or in two visits ( a ) with or ( b ) without calcium hydroxide as an intracanal disinfecting medicament . The patients were assigned one of the three treatment groups by the throwing of a die . The Periapical Index ( PAI ) Scoring Method was used to compare differences in periapical status from the beginning of treatment to a 52-wk follow-up evaluation . Overall , the periapical status of the treated teeth improved significantly after 52 wk ( p < 0.0001 ) . A PAI score of 1 or 2 was considered as representing a " good " periapical status while 3 , 4 , or 5 was a " bad " status . When base line PAI scores were controlled for , the calcium hydroxide group showed the most improvement in PAI score ( 3 , 4 , or 5 to 1 or 2 ) , followed by the one-step group ( 74 % vs. 64 % ) . The teeth that were left empty between visits had clearly inferior healing results . Power statistics were conducted to determine the numbers required for significant differences between the groups , and it was shown that large experimental groups on the order of hundreds of patients would be required to show significant differences In the present study , multivariate analyses were performed on clinical and treatment variables that may influence the outcome of endodontic treatment . Data collected in a previous clinical -radiographic follow-up study were used . Of 810 treated , 675 roots in 498 teeth were followed for 6 months to 4 yr . Of these , 192 ( the CAP group ) had pre-existing , chronic apical periodontitis and 483 ( the NAP group ) had not . Root canal treatment followed a st and ard procedure with one of three sealers chosen at r and om . Demographic , clinical and radiographic variables were recorded at the start of , and during treatment . The periapical index ( PAI ) score was used to record the outcome of treatment , and applied in two different endpoint modes ( END1 and END2 ) as the dependent variable for multivariate statistical analyses using logistic regression and the general model . The modes reflected increasing PAI scores ( END1 ) and conventional success/failure assessment ( END2 ) . Dropouts were largely similar to the cases followed up . A total of 10 preoperative and peroperative variables were found to be significantly associated with treatment outcome by the multivariate analyses of either the total material or the NAP or CAP subgroups . Several of these were not significant in univariate analyses ( e.g. the effect of sealer ) . Conventional success/failure analyses ( END2 ) identified fewer of the influential variables and had low explanatory power , whereas PAI scores on an ordinal scale ( END1 ) were most sensitive in identifying variables of influence on the treatment outcome |
10,376 | 28,973,989 | Menu labeling away-from-home did not result in change in quantity or quality , specifically for carbohydrates , total fat , saturated fat , or sodium , of calories consumed among U.S. adults | A systematic review and meta- analysis determined the effect of restaurant menu labeling on calories and nutrients chosen in laboratory and away-from-home setting s in U.S. adults . | BACKGROUND The federal menu labeling law will require chain restaurants to post caloric information on menus , but the impact of labeling is uncertain . PURPOSE The goal of the current study was to examine the effect of menu labeling on calories purchased , and secondarily , to assess self-reported awareness and use of labels . DESIGN Single-community pre-post-post cross-sectional study . Data were collected in 2008 - 2010 and analyzed in 2011 - 2012 . SETTING / PARTICIPANTS 50 sites from 10 chain restaurants in King County , Washington , selected through stratified , two-stage cluster r and om sampling . A total of 7325 customers participated . Eligibility criteria were : being an English speaker , aged ≥ 14 years , and having an itemized receipt . The study population was 59 % male , 76 % white non-Hispanic , and 53 % aged<40 years . INTERVENTION A regulation requiring chain restaurants to post calorie information on menus or menu boards was implemented . MAIN OUTCOME MEASURES Mean number of calories purchased . RESULTS No significant changes occurred between baseline and 4 - 6 months postregulation . Mean calories per purchase decreased from 908.5 to 870.4 at 18 months post-implementation ( 38 kcal , 95 % CI=-76.9 , 0.8 , p=0.06 ) in food chains and from 154.3 to 132.1 ( 22 kcal , 95 % CI=-35.8 , -8.5 , p=0.002 ) in coffee chains . Calories decreased in taco and coffee chains , but not in burger and s and wich establishments . They decreased more among women than men in coffee chains . Awareness of labels increased from 18.8 % to 61.7 % in food chains and from 4.4 % to 30.0 % in coffee chains ( both p<0.001 ) . Among customers seeing calorie information , the proportion using it ( about one third ) did not change substantially over time . After implementation , food chain customers using information purchased on average fewer calories compared to those seeing but not using ( difference=143.2 kcal , p<0.001 ) and those not seeing ( difference=135.5 kcal , p<0.001 ) such information . CONCLUSIONS Mean calories per purchase decreased 18 months after implementation of menu labeling in some restaurant chains and among women but not men Increased visibility of food labels is a potential method to reduce the rate of obesity . However , few empirical studies have investigated the impact of nutrition labeling on food selection or energy intake . This study tested the hypothesis that nutrition labeling in combination with nutrition label education would promote reductions in energy intake using a laboratory-based paradigm . Forty-seven male ( n=24 ) and female ( n=23 ) participants visited the Nutrition and Health Research Laboratory for a single lunch session during the months of May through August 2009 . Participants were r and omly assigned to one of two video groups ( Nutrition Labeling Education or Organic Food Movement ) and one of two labeling conditions ( Nutrition Labels or No Labels ) . Participants watched a short educational video and then consumed a buffet lunch . Data were analyzed using a three-way analysis of covariance with sex , video condition , and labeling group as the between-subject factors and age and race as covariates . There were main effects of sex and nutrition label condition on lunch energy intake with females consuming less than males and people with nutrition labels consuming less energy than those without , regardless of sex or video condition . Examination of energy intake from low-energy-density and high-energy-density foods showed that the nutrition labeling group consumed less energy from both low-energy-density and high-energy-density food sources . These data support the use of nutrition labels as a way to reduce energy intake Background Recent legislation has required calorie labels on restaurant menus as a means of improving Americans ’ health . Despite the growing research in this area , no consensus has been reached on the effectiveness of menu labels . This suggests the possibility of heterogeneity in responses to caloric labels across people with different attitudes and demographics . The purpose of this study was to explore the potential relationships between caloric intake and diners ’ socio-economic characteristics and attitudes in a restaurant field experiment that systematic ally varied the caloric information printed on the menus . Methods We conducted a field experiment in a full service restaurant where patrons were r and omly assigned to one of three menu treatments which varied the amount of caloric information printed on the menus ( none , numeric , or symbolic calorie label ) . At the conclusion of their meals , diners were asked to complete a brief survey regarding their socio-economic characteristics , attitudes , and meal selection s. Using regression analysis , we estimated the number of entrée and extra calories ordered by diners as a function of demographic and attitudinal variables . Additionally , irrespective of the menu treatment to which a subject was assigned , our study identified which types of people are likely to be low- , medium- , and high-calorie diners . Results Results showed that calorie labels have the greatest impact on those who are least health conscious . Additionally , using a symbolic calorie label can further reduce the caloric intake of even the most health conscious patrons . Finally , calorie labels were more likely to influence the selection of the main entrée as opposed to supplemental items such as drinks and desserts . Conclusions If numeric calorie labels are implemented ( as currently proposed ) , they are most likely to influence consumers who are less health conscious – probably one of the key targets of this legislation . Unfortunately , numeric labels did little for those consumers who were already more knowledgeable about health and nutrition . To reach a broader group of diners , a symbolic calorie label may be preferred as it reduced caloric intake across all levels of health consciousness We surveyed 7318 customers from 275 r and omly selected restaurants of 11 fast food chains . Participants purchased a mean of 827 calories , with 34 % purchasing 1000 calories or more . Unlike other chains , Subway posted calorie information at point of purchase and its patrons more often reported seeing calorie information than patrons of other chains ( 32 % vs 4 % ; P<.001 ) ; Subway patrons who saw calorie information purchased 52 fewer calories than did other Subway patrons ( P<.01 ) . Fast-food chains should display calorie information prominently at point of purchase , where it can be seen and used to inform purchases Objective To assess the impact of fast food restaurants adding calorie labelling to menu items on the energy content of individual purchases . Design Cross sectional surveys in spring 2007 and spring 2009 ( one year before and nine months after full implementation of regulation requiring chain restaurants ’ menus to contain details of the energy content of all menu items ) . Setting 168 r and omly selected locations of the top 11 fast food chains in New York City during lunchtime hours . Participants 7309 adult customers interviewed in 2007 and 8489 in 2009 . Main outcome measures Energy content of individual purchases , based on customers ’ register receipts and on calorie information provided for all items in menus . Results For the full sample , mean calories purchased did not change from before to after regulation ( 828 v 846 kcal , P=0.22 ) , though a modest decrease was shown in a regression model adjusted for restaurant chain , poverty level for the store location , sex of customers , type of purchase , and inflation adjusted cost ( 847 v 827 kcal , P=0.01 ) . Three major chains , which accounted for 42 % of customers surveyed , showed significant reductions in mean energy per purchase ( McDonald ’s 829 v 785 kcal , P=0.02 ; Au Bon Pain 555 v 475 kcal , P<0.001 ; KFC 927 v 868 kcal , P<0.01 ) , while mean energy content increased for one chain ( Subway 749 v 882 kcal , P<0.001 ) . In the 2009 survey , 15 % ( 1288/8489 ) of customers reported using the calorie information , and these customers purchased 106 fewer kilocalories than customers who did not see or use the calorie information ( 757 v 863 kcal , P<0.001 ) . Conclusion Although no overall decline in calories purchased was observed for the full sample , several major chains saw significant reductions . After regulation , one in six lunchtime customers used the calorie information provided , and these customers made lower calorie choices Chain restaurants will soon need to disclose calorie information on menus , but research on the impact of calorie labels on food choices is mixed . This study tested whether calorie information presented in different formats influenced calories ordered and perceived restaurant healthfulness . Participants in an online survey were r and omly assigned to a menu with either ( 1 ) no calorie labels ( No Calories ) ; ( 2 ) calorie labels ( Calories ) ; ( 3 ) calorie labels ordered from low to high calories ( Rank-Ordered Calories ) ; or ( 4 ) calorie labels ordered from low to high calories that also had red/green circles indicating higher and lower calorie choices ( Colored Calories ) . Participants ordered items for dinner , estimated calories ordered , and rated restaurant healthfulness . Participants in the Rank-Ordered Calories condition and those in the Colored Calories condition ordered fewer calories than the No Calories group . There was no significant difference in calories ordered between the Calories and No Calories groups . Participants in each calorie label condition were significantly more accurate in estimating calories ordered compared to the No Calories group . Those in the Colored Calories group perceived the restaurant as healthier . The results suggest that presenting calorie information in the modified Rank-Ordered or Colored Calories formats may increase menu labeling effectiveness OBJECTIVES We assessed the impact of restaurant menu calorie labels on food choices and intake . METHODS Participants in a study dinner ( n=303 ) were r and omly assigned to either ( 1 ) a menu without calorie labels ( no calorie labels ) , ( 2 ) a menu with calorie labels ( calorie labels ) , or ( 3 ) a menu with calorie labels and a label stating the recommended daily caloric intake for an average adult ( calorie labels plus information ) . Food choices and intake during and after the study dinner were measured . RESULTS Participants in both calorie label conditions ordered fewer calories than those in the no calorie labels condition . When calorie label conditions were combined , that group consumed 14 % fewer calories than the no calorie labels group . Individuals in the calorie labels condition consumed more calories after the study dinner than those in both other conditions . When calories consumed during and after the study dinner were combined , participants in the calorie labels plus information group consumed an average of 250 fewer calories than those in the other groups . CONCLUSIONS Calorie labels on restaurant menus impacted food choices and intake ; adding a recommended daily caloric requirement label increased this effect , suggesting menu label legislation should require such a label . Future research should evaluate menu labeling 's impact on children 's food choices and consumption Background Although point-of-purchase calorie labeling at restaurants has been proposed as a strategy for improving consumer food choices , a limited number of studies have evaluated this approach . Likewise , little research has been conducted to evaluate the influence of value size pricing on restaurant meal choices . Methods To examine the effect of point-of-purchase calorie information and value size pricing on fast food meal choices a r and omized 2 × 2 factorial experiment was conducted in which participants ordered a fast food meal from one of four menus that varied with respect to whether calorie information was provided and whether value size pricing was used . Study participants included 594 adolescents and adults who regularly ate at fast food restaurants . Study staff recorded the foods ordered and consumed by each participant . Participants also completed surveys to assess attitudes , beliefs and practice s related to fast food and nutrition . Results No significant differences in the energy composition of meals ordered or eaten were found between menu conditions . The average energy content of meals ordered by those r and omized to a menu that included calorie information and did not include value size pricing was 842 kcals compared with 827 kcals for those who ordered their meal from a menu that did not include calorie information but had value size pricing ( control menu ) . Results were similar in most analyses conducted stratified by factors such as age , race and education level . Conclusion Additional research is needed to better evaluate the effects of calorie labeling and value size pricing on fast food meal choices . Studies in which participants are repeatedly exposed to these factors are needed since long term exposure may be required for behavior change In a prospect i ve study of risk factors for ischemic heart disease , 792 54-yr-old men selected by year of birth ( 1913 ) and residence in Göteborg , Sweden , agreed to attend for question ing and a number of anthropometric and other measurements in 1967 . Thirteen and one-half years later , these baseline findings were review ed in relation to the number of men who had subsequently developed diabetes mellitus . This analysis focused on the importance of abdominal adipose tissue distribution , measured as the waistto- hip circumference ratio , as a predictor for development of diabetes . Even when the confounding effect of body mass index , as a measure of the total body fat mass , was accounted for , the waist-to-hip ratio was positively and significantly associated with the risk for diabetes . These results from a prospect i ve study strongly support previous cross-sectional findings indicating that not only the degree of obesity but also the localization of fat is a risk factor for diabetes OBJECTIVE To examine the influences of nutritional information and consumer characteristics on meal quality expectations , food selection and subsequent macronutrient intakes of consumers offered a reduced-fat option in a restaurant . DESIGN A target , full-fat ( FF ) main restaurant meal option was developed in a version substantially reduced in fat and energy ( RF ) . Restaurant patrons were r and omly placed into one of four treatment groups varying in provision of menu information about the target dish , and the actual version of that dish served ( if ordered ) . A full-fat blind ( FFB ) control group was given no nutritional information in the menu and was served the FF version . The other three groups were all served the modified RF version : ( i ) reduced-fat blind ( RFB ) , who were given no nutritional information ; ( ii ) reduced-fat informed ( RFI ) , who were given nutritional information ; and ( iii ) reduced-fat informed with details ( RFID ) , who were given the same nutritional information plus recipe modification details . Subjects rated their expected and actual liking , the pleasantness of taste , texture and appearance of the dish , how well the dish matched their expectations , and the likelihood of purchase again . Additional measures included the other dish selection s , sociodemographic and attitudinal information . SETTING A silver service ( training ) restaurant . SUBJECTS Members of the public ( n = 279 ) consuming meals in the restaurant . RESULTS The presence of nutritional information on the menu did not significantly increase subsequent intakes of energy and fat from the rest of the meal , and did not significantly influence sensory expectations or post-meal acceptance measures ( which also did not differ between the FF and RF versions ) . Consumer characteristics relating to fat reduction attitudes and behaviours were significantly related to the selection of different dishes . CONCLUSIONS Provision of RF alternatives in a restaurant can have significant positive dietary benefits . Menu nutritional information did not affect measures of meal acceptance . Further studies should identify which types of information formats might be most effective in enhancing the selection of ' healthy ' options This study assessed whether the inclusion of kilojoule labelling alone or accompanied by further nutrition information on menus led adults to select less energy-dense fast food meals . A between-subjects experimental design was used with online menu boards systematic ally varied to test the following labelling conditions : none ( control ) ; kilojoule ; kilojoule+percent daily intake ; kilojoule+traffic light ; and kilojoule+traffic light+percent daily intake . Respondents were 1294 adults aged 18 - 49 in Victoria , Australia who had purchased fast food in the last month and were r and omly assigned to conditions . Respondents in the no labelling condition selected meals with the highest mean energy content and those viewing the kilojoule and kilojoule+traffic light information selected meals with a significantly lower mean energy content , that constituted a reduction of around 500kJ ( 120kcal ) . Respondents most commonly reported using the traffic light labels in making their selection s. These findings provide support for the policy of disclosure of energy content on menus at restaurant chains . Given the magnitude of the reduction in energy density reported , and the prevalence of fast food consumption , this policy initiative has the potential to yield health benefits at the population level In a prospect i ve study of risk factors for ischaemic heart disease 792 54 year old men selected by year of birth ( 1913 ) and residence in Gothenburg agreed to attend for question ing and a battery of anthropometric and other measurements in 1967 . Thirteen years later these baseline findings were review ed in relation to the numbers of men who had subsequently suffered a stroke , ischaemic heart disease , or death from all causes . Neither quintiles nor deciles of initial indices of obesity ( body mass index , sum of three skinfold thickness measurements , waist or hip circumference ) showed a significant correlation with any of the three end points studied . Statistically significant associations were , however , found between the waist to hip circumference ratio and the occurrence of stroke ( p = 0.002 ) and ischaemic heart disease ( p = 0.04 ) . When the confounding effect of body mass index or the sum of three skinfold thicknesses was accounted for the waist to hip circumference ratio was significantly associated with all three end points . This ratio , however , was not an independent long term predictor of these end points when smoking , systolic blood pressure , and serum cholesterol concentration were taken into account . These results indicate that in middle aged men the distribution of fat deposits may be a better predictor of cardiovascular disease and death than the degree of adiposity In this study we examined the effect of physical activity based labels on the calorie content of meals selected from a sample fast food menu . Using a web-based survey , participants were r and omly assigned to one of four menus which differed only in their labeling schemes ( n=802 ) : ( 1 ) a menu with no nutritional information , ( 2 ) a menu with calorie information , ( 3 ) a menu with calorie information and minutes to walk to burn those calories , or ( 4 ) a menu with calorie information and miles to walk to burn those calories . There was a significant difference in the mean number of calories ordered based on menu type ( p=0.02 ) , with an average of 1020 calories ordered from a menu with no nutritional information , 927 calories ordered from a menu with only calorie information , 916 calories ordered from a menu with both calorie information and minutes to walk to burn those calories , and 826 calories ordered from the menu with calorie information and the number of miles to walk to burn those calories . The menu with calories and the number of miles to walk to burn those calories appeared the most effective in influencing the selection of lower calorie meals ( p=0.0007 ) when compared to the menu with no nutritional information provided . The majority of participants ( 82 % ) reported a preference for physical activity based menu labels over labels with calorie information alone and no nutritional information . Whether these labels are effective in real-life scenarios remains to be tested BACKGROUND Nutrition labeling of menus has been promoted as a means for helping consumers make healthier food choices at restaurants . As part of national health reform , chain restaurants will be required to post nutrition information at point-of-purchase , but more evidence regarding the impact of these regulations , particularly in children , is needed . PURPOSE To determine whether nutrition labeling on restaurant menus results in a lower number of calories purchased by children and their parents . METHODS A prospect i ve cohort study compared restaurant receipts of those aged 6 - 11 years and their parents before and after a menu-labeling regulation in Seattle/King County ( S/KC ) ( n=75 ) , with those from a comparison sample in nonregulated San Diego County ( SDC ) ( n=58 ) . Data were collected in 2008 and 2009 and analyzed in 2010 . RESULTS In S/KC , there was a significant increase from pre- to post-regulation ( 44 % vs 87 % ) in parents seeing nutrition information , with no change in SDC ( 40 % vs 34 % ) . Average calories purchased for children did not change in either county ( 823 vs 822 in S/KC , 984 vs 949 in SDC ) . There was an approximately 100-calorie decrease for the parents postregulation in both counties ( 823 vs 720 in S/KC , 895 vs 789 in SDC ) , but no difference between counties . CONCLUSIONS A restaurant menu-labeling regulation increased parents ' nutrition information awareness but did not decrease calories purchased for either children or parents OBJECTIVES We examined the effect on food purchases of adding recommended calorie intake per day or per meal to the m and ated calorie information posted on chain restaurant menus . METHODS Before and after New York City implemented calorie posting on chain restaurant menus in 2008 , we provided daily , per-meal , or no calorie recommendations to r and omized subsets of adult lunchtime customers ( n = 1121 ) entering 2 McDonald 's restaurants , in Manhattan and Brooklyn , and collected receipts and survey responses as they exited . In linear and logistic regressions , with adjustment for gender , race , age , and day , we tested for simple differences in calories consumed and interactions between variables . RESULTS Posting calorie benchmarks had no direct impact , nor did it moderate the impact of calorie labels on food purchases . The recommendation appeared to promote a slight increase in calorie intake , attributable to increased purchases of higher-calorie entrées . CONCLUSIONS These results do not support the introduction of calorie recommendations as a means of enhancing the impact of posted calorie information or reducing the contribution of restaurant dining to the obesity epidemic |
10,377 | 21,735,442 | However , it was common for women in the biofeedback arms to have more contact with the health professional than those in the non-biofeedback arms .
There was much variety in the regimens proposed for adding feedback or biofeedback to PFMT alone , and it was often not clear what the actual intervention comprised or what the purpose of the intervention was .
Feedback or biofeedback may provide benefit in addition to pelvic floor muscle training in women with urinary incontinence . | BACKGROUND Pelvic floor muscle training ( PFMT ) is an effective treatment for stress urinary incontinence in women .
Whilst most of the PFMT trials have been done in women with stress urinary incontinence , there is also some trial evidence that PFMT is effective for urgency urinary incontinence and mixed urinary incontinence .
Feedback or biofeedback are common adjuncts used along with PFMT to help teach a voluntary pelvic floor muscle contraction or to improve training performance .
OBJECTIVES To determine whether feedback or biofeedback adds further benefit to PFMT for women with urinary incontinence .
To compare the effectiveness of different forms of feedback or biofeedback . | CONTEXT Pelvic floor electrical stimulation ( PFES ) has been shown to be effective for stress incontinence . However , its role in a multicomponent behavioral training program has not been defined . OBJECTIVE To determine if PFES increases efficacy of behavioral training for community-dwelling women with stress incontinence . DESIGN AND SETTING Prospect i ve r and omized controlled trial conducted from October 1 , 1995 , through May 1 , 2001 , at a university-based outpatient continence clinic in the United States . PATIENTS Volunteer sample of 200 ambulatory , nondemented , community-dwelling women aged 40 to 78 years with stress or mixed incontinence with stress as the predominant pattern ; stratified by race , type of incontinence ( stress only vs mixed ) , and severity ( frequency of episodes ) . INTERVENTIONS Patients were r and omly assigned to 8 weeks ( 4 visits ) of behavioral training , 8 weeks ( 4 visits ) of the behavioral training plus home PFES , or 8 weeks of self-administered behavioral treatment using a self-help booklet ( control condition ) . MAIN OUTCOME MEASURES Primary outcome was percentage reduction in the number of incontinent episodes as documented in bladder diaries . Secondary outcomes were patient satisfaction and changes in quality of life . RESULTS Intention-to-treat analysis showed that incontinence was reduced a mean of 68.6 % with behavioral training , 71.9 % with behavioral training plus PFES , and 52.5 % with the self-help booklet ( P = .005 ) . In comparison with the self-help booklet , behavioral training ( P = .02 ) and behavioral training plus PFES ( P = .002 ) were significantly more effective , but they were not significantly different from each other ( P = .60 ) . The PFES group had significantly better patient self-perception of outcome ( P<.001 ) and satisfaction with progress ( P = .02 ) . Significant improvements were seen across all 3 groups on the Incontinence Impact Question naire but with no between-group differences . CONCLUSIONS Treatment with PFES did not increase effectiveness of a comprehensive behavioral program for women with stress incontinence . A self-help booklet reduced incontinence and improved quality of life but not as much as the clinic-based programs Biofeedback is a method of pelvic floor rehabilitation using a surface electrode inserted into the vagina and a catheter in the rectum . Forty women with genuine urinary stress incontinence were r and omized to compare the efficacy of physiotherapy and physiotherapy in combination with biofeedback . The effect of the treatment was determined by a st and ardized pad-weighing test . Long-term status was determined using a question naire after 2–3 years . Thirty-four women completed the treatment . The study showed a statistically significant better improvement in the biofeedback group . The long-term effect in the biofeedback group seemed better and the patients were more motivated for training afterwards This study was a r and omized controlled trial to investigate the effect of treating women with stress or mixed urinary incontinence ( SUI or MUI ) by diaphragmatic , deep abdominal and pelvic floor muscle ( PFM ) retraining . Seventy women were r and omly allocated to the training ( n = 35 ) or control group ( n = 35 ) . Women in the training group received 8 individual clinical visits and followed a specific exercise program . Women in the control group performed self-monitored PFM exercises at home . The primary outcome measure was self-reported improvement . Secondary outcome measures were 20-min pad test , 3-day voiding diary , maximal vaginal squeeze pressure , holding time and quality of life . After a 4-month intervention period , more participants in the training group reported that they were cured or improved ( p < 0.01 ) . The cure/improved rate was above 90 % . Both amount of leakage and number of leaks were significantly lower in the training group ( p < 0.05 ) but not in the control group . More aspects of quality of life improved significantly in the training group than in the control group . Maximal vaginal squeeze pressure , however , decreased slightly in both groups . Coordinated retraining diaphragmatic , deep abdominal and PFM function could improve symptoms and quality of life . It may be an alternative management for women with SUI or MUI CONTEXT Previous research on urge urinary incontinence has demonstrated that multicomponent behavioral training with biofeedback is safe and effective , yet it has not been established whether biofeedback is an essential component that heightens therapeutic efficacy . OBJECTIVE To examine the role of biofeedback in a multicomponent behavioral training program for urge incontinence in community-dwelling older women . DESIGN Prospect i ve , r and omized controlled trial conducted from April 1 , 1995 , to March 30 , 2001 . SETTING University-based outpatient continence clinic in the United States . PATIENTS A volunteer sample of 222 ambulatory , nondemented , community-dwelling women aged 55 to 92 years with urge incontinence or mixed incontinence with urge as the predominant pattern . Patients were stratified by race , type of incontinence ( urge only vs mixed ) , and severity ( frequency of accidents ) . INTERVENTIONS Patients were r and omly assigned to receive 8 weeks ( 4 visits ) of biofeedback-assisted behavioral training ( n = 73 ) , 8 weeks ( 4 visits ) of behavioral training without biofeedback ( verbal feedback based on vaginal palpation ; n = 74 ) , or 8 weeks of self-administered behavioral treatment using a self-help booklet ( control condition ; n = 75 ) . MAIN OUTCOME MEASURES Reduction in the number of incontinence episodes as documented in bladder diaries , patients ' perceptions and satisfaction , and changes in quality of life . RESULTS Intention-to-treat analysis showed that behavioral training with biofeedback yielded a mean 63.1 % reduction ( SD , 42.7 % ) in incontinence , verbal feedback a mean 69.4 % reduction ( SD , 32.7 % ) , and the self-help booklet a mean 58.6 % reduction ( SD , 38.8 % ) . The 3 groups were not significantly different from each other ( P = .23 ) . The groups differed significantly regarding patient satisfaction : 75.0 % of the biofeedback group , 85.5 % of the verbal feedback group , and 55.7 % of the self-help booklet group reported being completely satisfied with treatment ( P = .001 ) . Significant improvements were seen across all 3 groups on 3 quality -of-life instruments , with no significant between-group differences . CONCLUSIONS Biofeedback to teach pelvic floor muscle control , verbal feedback based on vaginal palpation , and a self-help booklet in a first-line behavioral training program all achieved comparable improvements in urge incontinence in community-dwelling older women . Patients ' perceptions of treatment were significantly better for the 2 behavioral training interventions OBJECTIVE To compare the effect of individual pelvic floor muscle training with and without biofeedback in women with urodynamic stress incontinence METHODS The study was a single , blind , r and omized trial . All women completed 6 months of pelvic floor muscle training comprising three sets of ten contractions three times per day , supervised by a physical therapist . One group trained with a biofeedback apparatus at home , the other without biofeedback . The primary outcome measures were pad test with st and ardized bladder volume and self‐report of severity . RESULTS A total of 103 women were r and omized , and data from 94 women were analyzed . Mean age ( range ) was 46.6 ( 30–70 ) years , and mean ( range ) duration of symptoms was 9.7 ( 1–25 ) years . Seventy women had urodynamic stress incontinence alone , and 24 women reported additional urge symptoms . Women training with and without biofeedback showed a statistically significant reduction in leakage on pad test ( P < .01 ) after 6 months of pelvic floor muscle training . Objective cure ( 2 g or less of leakage ) in the total group was 58 % in women training with and 46 % in women training without biofeedback , and in the subgroup of women with urodynamic stress incontinence alone , 69 % in women training with and 50 % in women training without biofeedback . There was no statistically significant difference between the groups posttreatment in any outcome measure . CONCLUSION Cure rate was high , and the reduction in urinary leakage after treatment was statistically significant in both groups . However , there was no statistically significant difference in the effect of individual pelvic floor muscle training with and without biofeedback Pages I-H , Jahr S , Schaufele MK , Conradi E : Comparative analysis of biofeedback and physical therapy for treatment of urinary stress incontinence in women . Am J Phys Med Rehabil 2001;80:494–502 . Objective To compare the effectiveness of an intensive group physical therapy program with individual biofeedback training for female patients with urinary stress incontinence . Design R and omized study of two therapeutic interventions consisting of a specific physical therapy program ( PT ) or biofeedback training ( BF ) daily for 4 wk , followed by a 2-mo , unsupervised home exercise program in both groups in an outpatient clinic of a large university hospital . Forty women , referred by gynecologists for nonoperative treatment of genuine stress incontinence of mild-to-moderate severity , were included . Measurements of daytime/nocturnal urinary frequency and subjective improvement of incontinence were the main outcome measures at initial presentation , after completion of the therapy program , and at follow-up after 3 mo . St and ardized examinations of digital contraction strength , speculum tests , and manometric measurements were documented as secondary outcome measures . Results In the PT group , the daytime urination frequency decreased 22 % after 4 wk of therapy and 19 % after 3 mo ( P < 0.05 ) from baseline . The nocturnal urination frequency was reduced by 66 % after 4 wk of therapy and 62 % after 3 mo ( P < 0.001 ) . In the BF group , the daily urination frequency decreased 10 % after 4 wk of therapy and 5 % after 3 mo ( P > 0.05 ) . The nocturnal urination frequency declined 36 % after 4 wk of therapy and 66 % after 3 months ( P < 0.05 ) . Subjective assessment after 3 mo showed that in the PT group , 28 % of patients were free of incontinence episodes , 68 % reported improved symptoms ( incontinence episodes improved by > 50 % ) , and 4 % were unchanged . In the BF group , 62 % were free of incontinence episodes , and 38 % were improved . Results of the digital contraction strength assessment s , speculum tests , and manometric measurements showed statistically significant improvement in all variables in both groups after 3 months . Conclusion Four weeks of both intensive group physical therapy or individual biofeedback training followed by an unsupervised home exercise program for 2 mo are effective therapies for female urinary stress incontinence and result in a significantly reduced nocturnal urinary frequency and improved subjective outcome . Only group physical therapy result ed in reduced daytime urinary frequency . BF therapy result ed in a better subjective outcome and higher contraction pressures of the pelvic floor muscles OBJECTIVE To identify predictors of outcome of a multi-component behavioral training program for urge and stress incontinence in women . METHODS This report is a secondary analysis of data from three prospect i ve , r and omized , clinical trials testing behavioral interventions for urinary incontinence . Participants were a volunteer sample of 258 ambulatory , nondemented , community-dwelling women , aged 40–92 years , with stress , urge , or mixed urinary incontinence . Participants received 8 weeks ( four visits ) of multicomponent behavioral training in each study . The relationship between a number of variables and treatment success were explored by univariate and multivariable logistic regression analyses . RESULTS Successful treatment of predominantly urge incontinence ( 75 % reduction of incontinent episodes as recorded on bladder diary ) was associated with not wearing any form of protection for incontinence ( P = .045 ; 95 % confidence interval [ CI ] .282 , .987 ) . Achieving total continence ( 100 % reduction ) was associated with fewer incontinent episodes at baseline ( P < .001 ; 95 % CI .138 , .557 ) , previous surgery for incontinence ( P = .021 ; 95 % CI 1.169 , 6.543 ) , and lower education level ( P = .022 ; 95 % CI .175 , .871 ) . Successful treatment of predominantly stress incontinence ( 75 % reduction ) was related to not having previous evaluation or treatment for incontinence ( P = .001 ; 95 % CI .026 , .415 ) , and fewer incontinent episodes on baseline bladder diary ( P = .026 ; 95 % CI .210 , .907 ) . Outcomes were not associated with age , race , type of incontinence , or a number of other variables reflecting medical history , obstetric history , medications , pelvic examination , body mass index , urodynamic parameters , or psychological distress . CONCLUSION Aside from indicators of severity and previous treatment , there were few associations between baseline clinical variables and outcome of behavioral treatment UNLABELLED We performed a r and omized clinical trial on the efficacy of physical therapy on genuine stress incontinence . STUDY OBJECTIVE " Is a physical therapeutical training program ( pelvic floor muscle training ) combined with biofeedback , more effective than the same program without biofeedback in patients with mild or moderate stress incontinence ? " Forty-four patients were referred by a general practitioner or a urologist . After informed consent , 40 patients were r and omized in an exercises and biofeedback group ( BF ) , or treated with exercises exclusively ( pelvic floor muscle training = PFMT ) . After a diagnostic phase of 1 week every patient received twelve treatment sessions , three times weekly . The primary measure of effect , the quantity of involuntary urine loss , was measured with the 48 hours PAD test ( Inco-test Mölnlycke ) . Before every treatment session the Symptoms question naire was filed out by the patient and the Patient dairy was controlled . The data of the trial were analysed according to the principal of intention to treat . During the trial there was 100 % compliance . There were no drop-outs . Both treatment modalities appeared to be effective . After twelve treatment sessions there was a mean improvement of + /- 55 % ( P = 0.00 ) in both treatment groups , measured by the primary measure of effect . In the group with BF this improvement was already realized after six treatment sessions ( P = 0.01 ) . Yet , the difference between BF and PFMT faded to reach significance at six treatment sessions ( P = 0.08 ) . Although differences in treatment effects between both groups were not significant , our findings suggest that adding biofeedback to pelvic floor muscle exercises might be more effective than pelvic floor muscle exercises alone after six treatments OBJECTIVES To compare the efficacy of pelvic floor muscle training ( PFMT ) , biofeedback-assisted PFMT ( BAPFMT ) , and electrical stimulation ( ES ) in the management of overactive bladder ( OAB ) . METHODS The interventions for the 12-week treatment period , conducted by the physiotherapist who was unaware of the progress and outcome , included ( a ) a PFMT program tailored to the subject 's PERFECT ( power , endurance , repetitions , and fast [ 1-second ] contractions , with every contraction timed ) scheme , used for training at home ; ( b ) an electromyography BAPFMT program and home program tailored to the subject 's PERFECT scheme ; and ( c ) an ES program using biphasic symmetric probe current with 10-Hz frequency , 400-micros pulse width , 10/5 duty cycle , and varying intensity . Identical preintervention and postintervention assessment included King 's Health Question naire , as well as outcomes of urge incontinence and other urinary symptoms . RESULTS Of the 103 women who completed this study , 34 were in the PFMT group , 34 in the BAPFMT group , and 35 in the ES group . The changes in the three parameters of King 's Health Question naire revealed statistically significant differences , except for the total score , between ES and BAPFMT ( domain 7 , P = 0.003 ; domain 9 , P = 0.029 ; and total score , P = 0.952 ) . These same parameters were significantly different between ES and PFMT ( domain 7 , P = 0.007 ; domain 9 , P = 0.001 ; and total score P = 0.004 ) . The change in total score was significantly different between BAPFMT and PFMT ( P = 0.003 ) . The subjective improvement/cure rate of OAB was 51.4 % for ES , 50.0 % for BAPFMT , and 38.2 % for PFMT ( P = 0.567 ) . CONCLUSIONS ES had the greatest subjective reduction rate of OAB and was the most effective of the three treatments . BAPFMT was more effective than PFMT One-third of 450 female soldiers surveyed indicated that they experienced problematic urinary incontinence during exercise and field training activities . The other crucial finding of this survey was probably that 13.3 % of the respondents restricted fluids significantly while participating in field exercises . Although only 5.3 % of respondents felt that their urine leakage had a significant impact on their regular duties , it is obvious that many more are sufficiently worried about leakage to put themselves at significant risk for dehydration-related injuries . This study tested whether behavioral interventions effective among older people could help younger soldiers . Thirty-nine female soldiers reporting exercise-induced urinary incontinence underwent urodynamic assessment s of bladder capacity , urethral closure pressure , and detrusor contraction pressures as well as a symptom question naire before and after therapy . They were stratified by diagnosis of physical stress incontinence or mixed urge/stress incontinence and r and omized into two groups . Twenty-three participants performed pelvic muscle exercises with urethral biofeedback for 8 weeks , and 16 participants performed pelvic muscle exercises alone . Patient reports as well as the post-treatment examinations indicated that all subjects improved significantly . Only five subjects in the biofeedback/exercise and three in the exercise-only group desired further treatment . All subjects initially diagnosed with detrusor dysfunction had normal readings at the end of the study . Thus , behavioral treatments can be effective against exercise-induced urinary incontinence among most female soldiers OBJECTIVES To determine the association between urogenital symptoms and the occurrence of depressive symptoms . METHODS A r and om sample of 3200 community-dwelling women , aged 20 to 70 years , was invited to answer a question naire . A total of 2042 question naires ( 63.8 % ) were returned . Urogenital symptoms were assessed with the Urogenital Distress Inventory and depressive symptoms with the Center for Epidemiological Studies Depression scale . A cutoff value of 16 or more on the Center for Epidemiological Studies Depression scale was considered as possible clinical depression . Univariate and multivariate logistic regression statistics were used . RESULTS The prevalence of depressive symptoms ( Center for Epidemiological Studies Depression scale score of 16 or more ) was significantly greater in women with urinary incontinence than in those without ( odds ratio 1.9 , 95 % confidence interval 1.6 to 2.3 ) . However , this statistically significant association existed for all urogenital symptoms when assessed individually . After multivariate adjustment , the statistical significant association with depressive symptoms was lost for most urogenital symptoms . Only nocturia remained significantly associated with depression throughout all analyses ( odds ratio 1.4 , 95 % confidence interval 1.1 to 1.8 for the symptom itself ; and odds ratio 2.0 , 95 % confidence interval 1.3 to 3.2 , when considering only bothersome nocturia symptoms ) . CONCLUSIONS After adjusting for the influence of coexisting urogenital symptoms , no association between urinary incontinence and depression could be demonstrated . Only nocturia remained significantly associated with depressive symptoms AIM Bladder dysfunction affects up to 90 % of the multiple sclerosis ( MS ) population . Interventions such as Pelvic Floor Training and Advice ( PFTA ) , Electromyography ( EMG ) Biofeedback , and Neuromuscular Electrical Stimulation ( NMES ) have received limited research attention within this population . This study aim ed to determine the effectiveness of a combined programme of PFTA , EMG Biofeedback , and NMES for bladder dysfunction in MS . METHODS Females ( n = 30 ) who fulfilled strict inclusion /exclusion criteria were recruited . Outcome measures ( weeks 0 , 9 , 16 , and 24 ) included : 3-day Voiding Diary ; 24 hr Pad-Test ; Uroflowmetry ; Pelvic Floor Muscle Assessment ; Incontinence Impact Question naire ( IIQ ) ; Urogenital Distress Inventory ( UDI ) ; King 's Health Question naire ( KHQ ) , and the Multiple Sclerosis Quality of Life-54 Instrument ( MSQoL-54 ) . Following baseline ( week 0 ) assessment , participants were r and omly allocated , under double blind conditions , to one of the three groups : Group 1 ( PFTA ) ; Group 2 ( PFTA and EMG Biofeedback ) ; and Group 3 ( PFTA , EMG Biofeedback , and NMES ) . Treatment was for 9 weeks . RESULTS Baseline severity ( measured by number of leaks and pad weight ) showed some variation between groups , although not statistically significant ( P > 0.05 ) ; with the caveat that this baseline imbalance makes interpretation difficult , a picture emerges that at week 9 , Group 3 demonstrated superior benefit as measured by the number of leaks and pad test than Group 2 , with Group 1 showing less improvement when compared to week 0 ; this was statistically significant between Groups 1 and 3 for number of leaks ( P = 0.014 ) and pad tests ( P = 0.001 ) , and Groups 1 and 2 for pad tests ( P = 0.001 ) . A similar pattern was evident for all other outcome measures . CONCLUSION Results suggest that these treatments , used in combination , may reduce urinary symptoms in MS . Further research will establish the effectiveness of these interventions Stress urinary incontinence is a common problem among women of all ages but may resolve with pelvic floor reeducation in many cases . Compliance to a regimen of pelvic floor muscle exercises is poor and many devices have been produced to make exercising these muscles more effective and interesting . This article describes a study in which two such devices -- vaginal cones and pressure biofeedback -- were compared with pelvic floor exercises alone . The results show that there is no statistically significant difference between the three modalities ; all treatments produced significant improvement in symptoms and quality of life scores BACKGROUND Research using biofeedback as a treatment for sphincteric incontinence began with Kegel 's early studies using a perineometer and pelvic muscle exercises demonstrating a 90 % improvement in urine loss symptoms . More recent studies using varying combinations of biofeedback and pelvic muscle exercises found symptom reduction rates of 78 % to 90 % , but these studies lacked the rigor of a " phase three , " or r and omized controlled clinical trial . METHODS A r and omized controlled trial assessed the efficacy of biofeedback for older women for treatment of sphincteric incompetence . One hundred thirty-five community-dwelling women were r and omized in a single-blind trial to three groups : biofeedback , pelvic muscle exercise , or control . Incontinent episodes were monitored over 8 weeks of treatment and at 3 and 6 months thereafter . RESULTS The number of incontinent episodes decreased significantly in the biofeedback and pelvic muscle exercise subjects but not in the control subjects for all severity of incontinence frequency subgroups . Improvement was maintained within the moderate and severe symptom subgroups for both treatments for at least 6 months but declined in subjects with mild incontinence frequency . Pelvic muscle activity ( EMG ) was significantly correlated with decreases in incontinent episodes , and only the biofeedback subjects showed significant improvement in EMGs . CONCLUSIONS Biofeedback and pelvic muscle exercises are efficacious for sphincteric incompetence in older women . Benefits are maintained and improvement continues for at least 6 months postintervention . These therapies may be useful before considering invasive treatment We investigated the effectiveness of pelvic floor muscle ( PFM ) exercises or biofeedback for the treatment of urinary stress incontinence ( USI ) . Fifty patients with USI were included in this r and omized , controlled , prospect i ve study . Twenty patients were taught PFM exercises via digital palpation and instructed to perform regularly as home program . The second group of 20 patients had PFM exercises via biofeedback three times a week for 2 months . The third group of 10 patients did not have any exercises . The patients were evaluated via pad test , perineometry , digital palpation based PFM strength , incontinence frequency , and visual analog scale based social activity index prior to and 8 weeks after the treatment . The first two groups had significant improvement in USI with respect to the control group ( p < 0.001 ) . The rise in PFM strength with perineometry of the biofeedback group was higher than in the digital palpation group after treatment ( p < 0.001 ) . PFM exercises are effective for the treatment of USI ; the biofeedback method revealed better PFM strength results with respect to digital palpation OBJECTIVE To assess the efficacy of physiotherapeutic treatment modalities in women with proven bladder overactivity . METHODS One hundred and twelve women received ambulatory urodynamics . Based on both urodynamic variables of ambulatory cystometry ( ACM ) and the micturition diary , the Detrusor Activity Index ( DAI ) for each patient was calculated . After r and omization , 68 women with a DAI > or = 0.50 were defined as having proven bladder overactivity . In a single blinded RCT patients were r and omized over four treatment groups , i.e. lower urinary tract exercises ( LUTE ) ; office- and home-based functional electrostimulation ( FES ) ; office-based FES and LUTE ; no treatment . Patients treated received nine treatment sessions , once weekly . The primary outcome variable was the DAI , measured before r and omization and , as soon as possible within a maximum of 14 days after the end of the study period . RESULTS Intention to treat analysis in the group of 68 patients showed a statistically significant decrease of DAI-scores in the FES group ( p=0.032 ) in comparison with no treatment , while this decrease was not statistically significant in the LUTE group ( p=0.105 ) and the LUTE+FES group ( p=0.672 ) . CONCLUSIONS Our conclusion is that , based on the DAI , in the homogeneous set of 68 patients , only FES seemed to be effective & NA ; Nurse practitioners ( NP ) are often confronted with female clients who describe various types of urine loss symptoms . To establish an accurate diagnosis and therapeutic intervention , it is important for the NP to identify the etiology of the urine loss complaint . The purpose of the study is to compare symptoms and physical findings that differentiate between the urodynamic diagnoses of genuine stress incontinence ( GSI ) and mixed incontinence ( MI ) in 135 clinical trial subjects : 123 diagnosed as GSI and 12 as MI . These subjects participated in a r and omized controlled clinical trial to investigate the efficacy of biofeedback and pelvic floor exercises for incontinence treatment . Data were analyzed for significant differences between these two groups on urologic and gynecologic symptoms , pelvic muscle relaxation , vaginal mucosa , vaginal electromyograph readings , urodynamic parameters , and quantified measure of urine loss . One‐way analysis of variance ( ANOVA ) showed significant difference in nocturnal and diurnal voidings and urine loss immediately after sensing the urge to void in the MI and GSI subjects . Chi‐square analyses found a significantly decreased incidence of poor vaginal tone and atrophic vaginal mucosa in the MI group as compared to the GSI group . The MI group also lost significantly more urine than did the GSI group on the h and wash maneuver of the perineal pad test . Although the sample size of MI subjects was small , these results show that a noninvasive history and physical examination can differentiate between urologic diagnoses . This approach provides a cost‐effective expedient protocol to aid the NP in establishing a differential diagnosis between genuine stress and mixed incontinence OBJECTIVES To compare electromyography-assisted biofeedback training to pelvic floor muscle training ( PFMT ) alone in patients with female stress urinary incontinence . METHODS A prospect i ve r and omized pilot study was conducted between March 1998 and February 2000 at the university hospital for outpatient care . Participants were women with urodynamically tested stress incontinence aged 31 to 69 years without previous incontinence operations , 30 volunteers altogether . The biofeedback group received an electromyography-guided biofeedback device for home training and the PFMT-alone group trained without any device at home . All patients were advised to practice for 20 minutes per day five times a week for 12 weeks . RESULTS According to the data analysis , muscle forces increased significantly in both supine ( P < 0.001 ) and st and ing ( P < 0.001 ) positions . In the supine position , the increase was significantly higher in the biofeedback group ( P = 0.024 ) . The results showed close to a significant decrease in the leakage index in the biofeedback group ( P = 0.068 ) , but in the PFMT-alone group , no change occurred . With respect to the pad test , the decrease was significant , but it was the same for both groups ( P = 0.907 ) . CONCLUSIONS The findings of this study show that pelvic floor muscle activity is increased and the amount of leaked urine is decreased after 3 months of PFMT . These preliminary results show a significant improvement compared with the PFMT-alone group in PFMT outcome measures in patients using electromyography-assisted biofeedback training This study compares two methods for h and ling missing data in longitudinal trials : one using the last-observation-carried-forward ( LOCF ) method and one based on a multivariate or mixed model for repeated measurements ( MMRM ) . Using data sets simulated to match six actual trials , I imposed several drop-out mechanisms , and compared the methods in terms of bias in the treatment difference and power of the treatment comparison . With equal drop-out in Active and Placebo arms , LOCF generally underestimated the treatment effect ; but with unequal drop-out , bias could be much larger and in either direction . In contrast , bias with the MMRM method was much smaller ; and whereas MMRM rarely caused a difference in power of greater than 20 % , LOCF caused a difference in power of greater than 20 % in nearly half the simulations . Use of the LOCF method is therefore likely to misrepresent the results of a trial seriously , and so is not a good choice for primary analysis . In contrast , the MMRM method is unlikely to result in serious misinterpretation , unless the drop-out mechanism is missing not at r and om ( MNAR ) and there is substantially unequal drop-out . Moreover , MMRM is clearly more reliable and better grounded statistically . Neither method is capable of dealing on its own with trials involving MNAR drop-out mechanisms , for which sensitivity analysis is needed using more complex methods We compared telemedicine with a conventional outpatient continence service ( CS ) in community-dwelling older women with urge or stress incontinence . After an initial biofeedback-assisted pelvic floor muscle training session , subjects were r and omized to behavioural training for eight weeks via the CS ( n = 27 ) or a telemedicine continence programme ( TCP ) ( n = 31 ) . Participants in both treatment groups experienced significant improvement in their symptoms , namely , a reduction in the number of daily incontinence episodes ( P<0.001 ) and voiding frequency ( P<0.001 ) , while the volume of urine at each micturition increased ( P<0.005 ) . Pelvic floor muscle strength as measured by the Oxford Score also improved ( P<0.005 ) . There were no significant differences in outcomes between the two groups . Thus our findings suggest that videoconferencing is as effective as conventional methods in the management of urinary incontinence BACKGROUND / AIMS The objective of this study is to examine if interpersonal support and digital vaginal palpation ( DVP ) as part of the pelvic floor muscle exercise ( PFME ) training is more effective for stress urinary incontinence ( SUI ) than PFME with a printed h and out instruction . METHODS 108 women who presented to the family medicine outpatient clinic without having urine leakage as a chief complaint were selected . They were r and omized to either the group who received interpersonal support and DVP as part of the PFME training ( experimental group ) , or the group who received PFME with a printed h and out instruction ( control group ) . The effects were assessed with 1-h pad tests . RESULTS A total of 99 patients ( 50 experimental , 49 control ) completed the study . The patients ' mean age was 55.35+/-9.60 years , ranging from 20 to 80 years . All patients without urinary leakage listed as a chief complaint exhibited more or less urine leakage during the 1-h pad test . A significant decrease in the weight of 1-h pad test from baseline was observed in the experimental group ( p<0.001 ) compared to the control group ( p=0.514 ) . CONCLUSION Interpersonal support and DVP as part of the PFME training is more effective than PFME with a printed h and out instruction . PFME , performed correctly and consistently , is effective even in patients who have very few symptoms of SUI |
10,378 | 28,919,087 | INTERPRETATION Liberal transfusion strategies might produce better outcomes in geriatric patients than restrictive transfusion strategies .
This outcome contradicts current restrictive transfusion approaches . | BACKGROUND Guidelines for patient blood management recommend restrictive transfusion practice for most adult patients .
These guidelines are supported by evidence from r and omised controlled trials ( RCTs ) ; however , one of the patient groups not explicitly examined in these studies is the geriatric population .
We examined RCTs relevant to transfusion outcomes in older patients .
Our aim was to determine whether special guidelines are warranted for geriatric patients , recognising the different pathophysiological characteristics of this group . | BACKGROUND Peri-operative red blood cell transfusions have been associated with post-operative complications in patients undergoing elective orthopaedic hip or knee replacement surgery . MATERIAL S AND METHODS We performed a post-hoc analysis of data extracted from a r and omised study on transfusion triggers using pre-storage leucocyte-depleted red blood cells . Patients who were assigned to the most restrictive transfusion policy ( " restrictive group " ) were compared with patients who were assigned to the most liberal policy ( " liberal group " ) . End-points were red blood cell use , hospital stay , haemoglobin levels , post-operative complications and quality of life scores . RESULTS Of 603 patients , 26.4 % patients in the restrictive group and 39.1 % in the liberal group were transfused ( P = 0.001 ) . The rate of post-operative infections was lower , although not statistically significantly so , in the restrictive group than in the liberal group ( 5.4 % vs. 10.2 % , respectively ) as was the rate of respiratory complications ( 1.7 % vs. 4.9 % , respectively ) , whereas hospital stay , cardiovascular complications and mortality rate were not different in the two groups . Quality of life scores were not associated with type of transfusion policy , the number of red blood cell transfusions or the transfusion status . DISCUSSION A restrictive transfusion protocol was not associated with worse outcome and result ed in a lower transfusion rate compared to the liberal policy . Well-being ( quality of life ) was not associated with transfusion policy or with red blood cell transfusions Background and purpose — Hip fracture ( HF ) in frail elderly patients is associated with poor physical recovery and death . There is often postoperative blood loss and the hemoglobin ( Hb ) threshold for red blood cell ( RBC ) transfusions in these patients is unknown . We investigated whether RBC transfusion strategies were associated with the degree of physical recovery or with reduced mortality after HF surgery . Patients and methods — We enrolled 284 consecutive post-surgical HF patients ( aged ≥ 65 years ) with Hb levels < 11.3 g/dL ( 7 mmol/L ) who had been admitted from nursing homes or sheltered housing . Allocation was stratified by residence . The patients were r and omly assigned to either restrictive ( Hb < 9.7 g/dL ; < 6 mmol/L ) or liberal ( Hb < 11.3 g/dL ; < 7 mmol/L ) RBC transfusions given within the first 30 days postoperatively . Follow-up was at 90 days . Results — No statistically significant differences were found in repeated measures of daily living activities or in 90-day mortality rate between the restrictive group ( where 27 % died ) and the liberal group ( where 21 % died ) . Per- protocol 30-day mortality was higher with the restrictive strategy ( hazard ratio ( HR ) = 2.4 , 95 % CI : 1.1–5.2 ; p = 0.03 ) . The 90-day mortality rate was higher for nursing home residents in the restrictive transfusion group ( 36 % ) than for those in the liberal group ( 20 % ) ( HR = 2.0 , 95 % CI : 1.1–3.6 ; p = 0.01 ) . Interpretation — According to our Hb thresholds , recovery from physical disabilities in frail elderly hip fracture patients was similar after a restrictive RBC transfusion strategy and after a liberal strategy . Implementation of a liberal RBC transfusion strategy in nursing home residents has the potential to increase survival Objectives It is still under debate that red blood cell ( RBC ) transfusions might increase the risk of healthcare-associated infections after hip fracture surgery . Previously , we found that a liberal RBC transfusion strategy improved survival in nursing home residents . Our aim , therefore , was to investigate whether a more liberal RBC transfusion strategy was associated with a higher infection risk in frail elderly hip fracture patients . Design Prospect i ve , assessor-blinded , r and omized and controlled trial . Setting sOrthopedic ward , Geriatric ward , and Hospital-at-home . Patients 284 consecutively hospital-admitted elderly with hip fracture from nursing homes or sheltered housing facilities were included . InterventionA restrictive RBC transfusion strategy ( hemoglobin < 9.7 g/dL ; 6 mmol/L ) compared with a liberal strategy ( hemoglobin < 11.3 g/dL ; 7 mmol/L ) administered within 30 days after surgery . Main outcome measurements Leukocytes and C-reactive protein ( CRP ) in repeated blood sample s within 30 days , and number of all infections ( pneumonia , urinary tract infection , and other infections ) within 10 days . Results 88 % of the patients received a RBC transfusion . A median of 1 RBC unit ( interquartile range ( IQR ) : 1–2 ) was transfused for the restrictive strategy group versus 3 RBC units ( IQR : 2–5 ) for the liberal group . Leukocytes and CRP measurements were similar for both groups . Rates of infection were 72 % for the restrictive group compared to 66 % for the liberal group ( risk ratio 1.08 ; 95 % confidence interval 0.93–1.27 , p value 0.29 ) . Conclusions A more liberal RBC transfusion strategy was not associated with higher risk of infection among residents from nursing homes or sheltered housing undergoing hip fracture surgery BACKGROUND The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial . We conducted a r and omized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture . METHODS We enrolled 2016 patients who were 50 years of age or older , who had either a history of or risk factors for cardiovascular disease , and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery . We r and omly assigned patients to a liberal transfusion strategy ( a hemoglobin threshold of 10 g per deciliter ) or a restrictive transfusion strategy ( symptoms of anemia or at physician discretion for a hemoglobin level of < 8 g per deciliter ) . The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up . RESULTS A median of 2 units of red cells were transfused in the liberal- strategy group and none in the restrictive- strategy group . The rates of the primary outcome were 35.2 % in the liberal- strategy group and 34.7 % in the restrictive- strategy group ( odds ratio in the liberal- strategy group , 1.01 ; 95 % confidence interval [ CI ] , 0.84 to 1.22 ) , for an absolute risk difference of 0.5 percentage points ( 95 % CI , -3.7 to 4.7 ) . The rates of in-hospital acute coronary syndrome or death were 4.3 % and 5.2 % , respectively ( absolute risk difference , -0.9 % ; 99 % CI , -3.3 to 1.6 ) , and rates of death on 60-day follow-up were 7.6 % and 6.6 % , respectively ( absolute risk difference , 1.0 % ; 99 % CI , -1.9 to 4.0 ) . The rates of other complications were similar in the two groups . CONCLUSIONS A liberal transfusion strategy , as compared with a restrictive strategy , did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk . ( Funded by the National Heart , Lung , and Blood Institute ; FOCUS Clinical Trials.gov number , NCT00071032 . ) Objectives To investigate whether a liberal blood transfusion strategy [ Hb levels ≥11.3 g/dL ( 7 mmol/L ) ] reduces the risk of postoperative delirium ( POD ) on day 10 , among nursing home residents with hip fracture , compared to a restrictive transfusion strategy [ Hb levels ≥9.7 g/dL ( 6 mmol/L ) ] . Furthermore , to investigate whether POD influences mortality within 90 days after hip surgery . Methods This is a post hoc analysis based on The TRIFE - a r and omized controlled trial . Frail anemic patients from the Orthopedic Surgical Ward at Aarhus University Hospital were enrolled consecutively between January 18 , 2010 and June 6 , 2013 . These patients ( aged ≥65 years ) had been admitted from nursing homes for unilateral hip fracture surgery . After surgery , 179 patients were included in this study . On the first day of hospitalization , all enrolled patients were examined for cognitive impairment ( assessed by MMSE ) and delirium ( assessed by CAM ) . Delirium was also assessed on the tenth postoperative day . Results The prevalence of delirium was 10 % in patients allocated to a liberal blood transfusion strategy ( LB ) and 21 % in the group with a restrictive blood transfusion strategy ( RB ) . LB prevents development of delirium on day 10 , compared to RB , odds ratio 0.41 ( 95 % CI 0.17–0.96 ) , p = 0.04 . Development of POD on day 10 increased the risk of 90-day death , hazard ratio 3.14 ( 95 % CI 1.72–5.78 ) , p < 0.001 . Conclusion In nursing home residents undergoing surgery for hip fracture , maintaining hemoglobin level above 11.3 g/dL reduces the rate of POD on day 10 compared to a RB . Development of POD is associated with increased mortality BACKGROUND To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients , we compared the rates of death from all causes at 30 days and the severity of organ dysfunction . METHODS We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and r and omly assigned 418 patients to a restrictive strategy of transfusion , in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter , and 420 patients to a liberal strategy , in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter . RESULTS Overall , 30-day mortality was similar in the two groups ( 18.7 percent vs. 23.3 percent , P= 0.11 ) . However , the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or = 20 ( 8.7 percent in the restrictive- strategy group and 16.1 percent in the liberal- strategy group ; P=0.03 ) -- and among patients who were less than 55 years of age ( 5.7 percent and 13.0 percent , respectively ; P=0.02 ) , but not among patients with clinical ly significant cardiac disease ( 20.5 percent and 22.9 percent , respectively ; P=0.69 ) . The mortality rate during hospitalization was significantly lower in the restrictive- strategy group ( 22.3 percent vs. 28.1 percent , P=0.05 ) . CONCLUSIONS A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients , with the possible exception of patients with acute myocardial infa rct ion and unstable angina BACKGROUND A before and after study was undertaken to investigate the effect of universal leukoreduction ( ULR ) in the UK on postoperative length of hospital stay ( LOS ) and infections . STUDY DESIGN AND METHODS Consecutive patients undergoing elective coronary artery bypass grafting or total hip and /or knee replacement in 11 hospitals received non-WBC-reduced RBCs before implementation of ULR ( T1 , n=997 ) or WBC-reduced RBCs after implementation of ULR ( T2 , n=1098 ) . RESULTS Patients in T1 and T2 were comparable except patients in T2 received on average more units of RBCs but had lower discharge Hct levels . Postoperative LOS ( T1 , 10 + /- 8.9 days ; T2 , 9.6 + /- 6.9 days ) and the proportion of patients with suspected and proven postoperative infections ( T1 , 21.0 % ; T2 , 20.0 % ) were unchanged before and after ULR ( LOS , hazard ratio 1.01 , 95 % CI 0.92 - 1.10 ; infections , OR 0.83 , 95 % CI 0.77 - 1.02 ) . Subgroup analysis showed no significant interaction between storage age or dose of blood on responsiveness of primary outcomes to ULR . Secondary outcomes were unchanged overall . Analysis by surgical procedure gave conflicting results with both increased mortality ( p=0.031 ) and an increased proportion of cardiac patients with proven infections ( p=0.004 ) , whereas the proportion of orthopedic patients with proven infections was reduced ( p=0.002 ) after ULR . CONCLUSION Implementation of ULR had no major impact on postoperative infection or LOS in patients undergoing elective surgical procedures who received transfusion(s ) . Smaller effects , either detrimental or beneficial of ULR , can not be excluded BACKGROUND Prior trials suggest it is safe to defer transfusion at hemoglobin levels above 7 to 8 g/dL in most patients . Patients with acute coronary syndrome may benefit from higher hemoglobin levels . METHODS We performed a pilot trial in 110 patients with acute coronary syndrome or stable angina undergoing cardiac catheterization and a hemoglobin < 10 g/dL. Patients in the liberal transfusion strategy received one or more units of blood to raise the hemoglobin level ≥10 g/dL. Patients in the restrictive transfusion strategy were permitted to receive blood for symptoms from anemia or for a hemoglobin < 8 g/dL. The predefined primary outcome was the composite of death , myocardial infa rct ion , or unscheduled revascularization 30 days post r and omization . RESULTS Baseline characteristics were similar between groups except age ( liberal , 67.3 ; restrictive , 74.3 ) . The mean number of units transfused was 1.6 in the liberal group and 0.6 in the restrictive group . The primary outcome occurred in 6 patients ( 10.9 % ) in the liberal group and 14 ( 25.5 % ) in the restrictive group ( risk difference = 15.0 % ; 95 % confidence interval of difference 0.7 % to 29.3 % ; P = .054 and adjusted for age P = .076 ) . Death at 30 days was less frequent in liberal group ( n = 1 , 1.8 % ) compared to restrictive group ( n = 7 , 13.0 % ; P = .032 ) . CONCLUSIONS The liberal transfusion strategy was associated with a trend for fewer major cardiac events and deaths than a more restrictive strategy . These results support the feasibility of and the need for a definitive trial Few studies have examined the association between perioperative blood transfusion and postoperative delirium ( POD ) in aged patients undergoing total hip replacement surgery . In this prospect i ve study , 186 patients older than 65 years undergoing elective unilateral total hip replacement surgery were enrolled . Of those , 94 patients were r and omly assigned to the restrictive strategy transfusion strategy group , in which red blood cells were transfused in order to maintain 10.0 g/dL > hemoglobin≧8.0 g/dL. Ninety-two patients were r and omly assigned to the liberal transfusion strategy group , in which red blood cells were transfused in order to maintain hemoglobin≧10.0 g/dL. POD was diagnosed by confusion assessment method . The baseline characteristics of patients , the length of hospital stay , the incidence of POD , myocardial infa rct ion , stroke , wound infection , pulmonary embolism , and the transfusion volume were recorded . No difference was observed in the baseline characteristics , the length of hospital stay , and the incidence of POD , myocardial infa rct ion , stroke , wound infection , and pulmonary embolism between the two groups ( P>0.05 ) . The proportion of patients transfused with red blood cell and frozen plasma was decreased in the restrictive transfusion group compared with the liberal transfusion group ( P<0.05 ) . In conclusion , restrictive transfusion does not influence the incidence of POD but reduces blood transfusion . Thus , restrictive transfusion may serve as an effective and safe strategy for aged patients following total hip replacement BACKGROUND Epidemiologic information on blood component usage can help improve the utilization of transfusion re sources . STUDY DESIGN AND METHODS Crosssectional survey in 2007 that included every hospital in Catalonia . Clinical data of blood recipients , including the four-digit International Classification of Diseases , 9th Revision , Clinical Modification codes and the indication for transfusion , were prospect ively collected according to an established protocol . RESULTS In total , 19,148 red blood cell ( RBC ) units , 1812 platelet ( PLT ) doses , and 3070 plasma units , transfused into 8019 patients ( median age , 71 years ; 52 % males ) , were surveyed . Half the RBC units were used by patients older than 70 years . Specific diagnosis and procedures with the highest RBC use were lower limb orthopedic surgery ( 10.6 % of all units ) and gastrointestinal hemorrhage ( 6 % ) . Therapeutic plasmapheresis ( 8.1 % ) and heart valve surgery ( 7.2 % ) were the procedures with the highest plasma use . Oncohematology patients accounted for 73 % of transfused PLTs , more that two-thirds being administered for hemorrhage prophylaxis . Acute hemorrhage was the most common indication for RBC and plasma transfusion . Among all blood recipients , 80 % received only RBCs and 6.9 % received only plasma and /or PLTs , without concomitant RBCs . The population transfusion incidence rates were 35 RBC units , three PLT doses , and 6 plasma units per 1000 population -year . Demographic changes anticipate a 30 % increase in RBC transfusion by year 2030 . CONCLUSIONS These results allow for identification of blood uses that are susceptible to improvement , help appraise the expected yield of blood safety measures , and will assist in planning the future blood supply OBJECTIVE The aim of this study was to compare outcomes in patients undergoing cardiac surgery who are aged 60 years or more or less than 60 years after implementation of a restrictive or a liberal transfusion strategy . METHODS This is a sub study of the Transfusion Requirements After Cardiac Surgery ( TRACS ) r and omized controlled trial . In this subgroup analysis , we separated patients into those aged 60 years or more ( elderly ) and those aged less than 60 years r and omized to a restrictive or a liberal strategy of red blood cell transfusion . The primary outcome was a composite defined as a combination of 30-day all-cause mortality and severe morbidity . RESULTS Of the 502 patients included in the Transfusion Requirements After Cardiac Surgery study , 260 ( 51.8 % ) were aged 60 years or more and 242 ( 48.2 % ) were aged less than 60 years and were included in this study . The primary end point occurred in 11.9 % of patients in the liberal strategy group and 16.8 % of patients in the restrictive strategy group ( P = .254 ) for those aged 60 years or more and in 6.8 % of patients in the liberal strategy group and 5.6 % of patients in the restrictive strategy group for those aged less than 60 years ( P = .714 ) . However , in the older patients , cardiogenic shock was more frequent in patients in the restrictive transfusion group ( 12.8 % vs 5.2 % , P = .031 ) . Thirty-day mortality , acute respiratory distress syndrome , and acute renal injury were similar in the restrictive and liberal transfusion groups in both age groups . CONCLUSIONS Although there was no difference between groups regarding the primary outcome , a restrictive transfusion strategy may result in an increased rate of cardiogenic shock in elderly patients undergoing cardiac surgery compared with a more liberal strategy . Cardiovascular risk of anemia may be more harmful than the risk of blood transfusion in older patients Importance More than 100 million units of blood are collected worldwide each year , yet the indication for red blood cell ( RBC ) transfusion and the optimal length of RBC storage prior to transfusion are uncertain . Objective To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion . Evidence Review Reference librarians conducted a literature search for r and omized clinical trials ( RCTs ) evaluating hemoglobin thresholds for RBC transfusion ( 1950-May 2016 ) and RBC storage duration ( 1948-May 2016 ) without language restrictions . The results were summarized using the Grading of Recommendations Assessment , Development and Evaluation method . For RBC transfusion thresholds , 31 RCTs included 12 587 participants and compared restrictive thresholds ( transfusion not indicated until the hemoglobin level is 7 - 8 g/dL ) with liberal thresholds ( transfusion not indicated until the hemoglobin level is 9 - 10 g/dL ) . The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes , including 30-day mortality , myocardial infa rct ion , cerebrovascular accident , rebleeding , pneumonia , or thromboembolism . For RBC storage duration , 13 RCTs included 5515 participants r and omly allocated to receive fresher blood or st and ard-issue blood . These RCTs demonstrated that fresher blood did not improve clinical outcomes . Findings It is good practice to consider the hemoglobin level , the overall clinical context , patient preferences , and alternative therapies when making transfusion decisions regarding an individual patient . Recommendation 1 : a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable , including critically ill patients , rather than when the hemoglobin level is 10 g/dL ( strong recommendation , moderate quality evidence ) . A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery , cardiac surgery , and those with preexisting cardiovascular disease ( strong recommendation , moderate quality evidence ) . The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL , but RCT evidence is not available for all patient categories . These recommendations do not apply to patients with acute coronary syndrome , severe thrombocytopenia ( patients treated for hematological or oncological reasons who are at risk of bleeding ) , and chronic transfusion-dependent anemia ( not recommended due to insufficient evidence ) . Recommendation 2 : patients , including neonates , should receive RBC units selected at any point within their licensed dating period ( st and ard issue ) rather than limiting patients to transfusion of only fresh ( storage length : < 10 days ) RBC units ( strong recommendation , moderate quality evidence ) . Conclusions and Relevance Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high- quality evidence to inform guidelines . A restrictive transfusion threshold is safe in most clinical setting s and the current blood banking practice s of using st and ard-issue blood should be continued |
10,379 | 30,662,479 | The most common early side effects due to HDR-BT treatment were vaginal inflammation , vaginal irritation , dryness , discharge , soreness , swelling , and fungal infection .
The most common late side effects consisted of vaginal discharge , dryness , itching , bleeding , fibrosis , telangiectasias , stenosis , short or narrow vagina , and dyspareunia .
Conclusions The data suggest that HDR endovaginal brachytherapy , with or without chemotherapy , is very well tolerated with low rates of acute and late vaginal toxicities . | Purpose To evaluate vaginal toxicity ( primary endpoint ) and local control ( secondary endpoint ) in patients with endometrial cancer who underwent primary surgery and adjuvant high-dose-rate ( HDR ) endovaginal brachytherapy ( BT ) . | PURPOSE Patients with completely resected high-risk endometrial cancer have a risk of disease recurrence even with the addition of adjuvant pelvic radiotherapy ( RT ) . A Phase II study was completed by the Radiation Therapy Oncology Group to assess the safety and toxicity of chemotherapy when combined with pelvic RT for these patients . METHODS AND MATERIAL S Eligibility requirements included a total abdominal hysterectomy and bilateral salpingo-oophorectomy with Grade 2 or 3 endometrial adenocarcinoma with > 50 % myometrial invasion , stromal invasion of the cervix , or pelvic-confined extrauterine disease . This study was design ed to administer 4500 cGy in 25 fractions to the pelvis , along with cisplatin ( 50 mg/m(2 ) ) on Days 1 and 28 . Vaginal brachytherapy with a low-dose-rate applicator ( 1 x 20 Gy to the surface ) or high-dose-rate applicator ( 3 x 6 Gy to the surface ) was performed after external beam RT . Four courses of cisplatin ( 50 mg/m(2 ) ) and paclitaxel ( 175 mg/m(2 ) ) were given at 4-week intervals after RT completion . RESULTS Forty-six patients were entered between October 1997 and April 1999 . Two patients were ineligible ( one with previous bladder cancer and one who had undergone surgery > 8 weeks before the start of RT ) . Follow-up ranged from 6.9 to 48.8 months ( median , 28.7 months ) . The disease was Stage III , II , and I in 66 % , 16 % , and 18 % of patients , respectively . Two patients were not assessable because of incomplete treatment data . The protocol completion rate was 98 % ( 41 of 42 assessable patients ) . Acute toxicity during RT/chemotherapy was Grade 1 in 27 % , Grade 2 in 43 % , Grade 3 in 27 % , and Grade 4 in 2 % . During adjuvant chemotherapy , the toxicity was Grade 1 in 7 % , Grade 2 in 7 % , Grade 3 in 21 % , and Grade 4 in 62 % . Severe toxicity was primarily hematologic . Chronic toxicity was Grade 1 in 20 % , Grade 2 in 39 % , Grade 3 in 16 % , and Grade 4 in 2 % , including 1 patient with a Grade 4 small bowel complication . At 24 months , the pelvic recurrence , regional recurrence , distant recurrence , disease-free survival , and overall survival rate was 2 % , 3 % , 17 % , 83 % , and 90 % , respectively . CONCLUSION This treatment protocol demonstrated an excellent treatment completion rate and expected toxicity . Longer follow-up is needed to assess the outcome . To assess the efficacy of this adjuvant treatment program , a Phase III trial ( Radiation Therapy Oncology Group 9905 ) was design ed with high-risk uterine-confined disease to be r and omized between pelvic RT alone and pelvic RT with chemotherapy BACKGROUND Postoperative radiotherapy for International Federation of Gynaecology and Obstetrics ( FIGO ) stage-1 endometrial carcinoma is a subject of controversy due to the low relapse rate and the lack of data from r and omised trials . We did a multicentre prospect i ve r and omised trial to find whether postoperative pelvic radiotherapy improves locoregional control and survival for patients with stage-1 endometrial carcinoma . METHODS Patients with stage-1 endometrial carcinoma ( grade 1 with deep [ > or = 50 % ] myometrial invasion , grade 2 with any invasion , or grade 3 with superficial [ < 50 % ] invasion ) were enrolled . After total abdominal hysterectomy and bilateral salpingo-oophorectomy , without lymphadenectomy , 715 patients from 19 radiation oncology centres were r and omised to pelvic radiotherapy ( 46 Gy ) or no further treatment . The primary study endpoints were locoregional recurrence and death , with treatment-related morbidity and survival after relapse as secondary endpoints . FINDINGS Analysis was done according to the intention-to-treat principle . Of the 715 patients , 714 could be evaluated . The median duration of follow-up was 52 months . 5-year actuarial locoregional recurrence rates were 4 % in the radiotherapy group and 14 % in the control group ( p<0.001 ) . Actuarial 5-year overall survival rates were similar in the two groups : 81 % ( radiotherapy ) and 85 % ( controls ) , p=0.31 . Endometrial-cancer-related death rates were 9 % in the radiotherapy group and 6 % in the control group ( p=0.37 ) . Treatment-related complications occurred in 25 % of radiotherapy patients , and in 6 % of the controls ( p<0.0001 ) . Two-thirds of the complications were grade 1 . Grade 3 - 4 complications were seen in eight patients , of which seven were in the radiotherapy group ( 2 % ) . 2-year survival after vaginal recurrence was 79 % , in contrast to 21 % after pelvic recurrence or distant metastases . Survival after relapse was significantly ( p=0.02 ) better for patients in the control group . Multivariate analysis showed that for locoregional recurrence , radiotherapy and age below 60 years were significant favourable prognostic factors . INTERPRETATION Postoperative radiotherapy in stage-1 endometrial carcinoma reduces locoregional recurrence but has no impact on overall survival . Radiotherapy increases treatment-related morbidity . Postoperative radiotherapy is not indicated in patients with stage-1 endometrial carcinoma below 60 years and patients with grade -2 tumours with superficial invasion AIM During the last decades , therapies targeting cervical cancer have been considerably improved . Surgery and radiotherapy ( RT ) represent the main common therapeutic approach in cervical cancer . In order to minimize the side effects of radiotherapy approach , several protocol s have been developed such as brachytherapy ( BRT ) . Among the side effects associated with RT , the vaginal atrophy is the most important and common one . Vaginal atrophy , in turn , leads to additional alterations like inflammation , associated to relevant symptoms such as itching , burning and dyspareunia . All these alterations heavily affect the quality of women 's life . The aim of our study was to evaluate the toxicity induced by RT on vaginal mucosa , and the adjuvant action of a product containing LMWHA , vitamin A , and Vitamin E ( Santes ® , Lo . Li . Pharma , Rome , Italy ) . The introduction of adjuvant therapies may have likely had a relevant place in providing that result . METHODS A prospect i ve r and omized study was design ed . From October 2006 to October 2008 , 45 women with a mean age 38 ± 6 years were enrolled . After surgery , all patients were treated with 4 weeks of RT and 4 weeks of BRT , concomitantly with chemiotherapy . They were r and omly assigned in two groups : 23 women were treated with two suppositories ( Santes ® ) per day for 4 months . For the first two months the preventive treatment was simultaneous to RT and BRT . Instead the control groups for composed by 22 patients and they did not undergo any treatment during RT . To evaluate the efficacy of Santes ® treatment three biopsies were performed . RESULTS At the second biopsy , after the BRT therapy , the treated group showed a statistically significant improvement ( P<0.05 vs. control ) on inflammation , cell atypia , fibrosis , mucositis and bleeding . At the third biopsy , two months after BRT , further statistically improvement were observed for all RT/BRT associated side effects . The treatment showed an efficacy also in terms of pain severity . CONCLUSION Our data suggest that low molecular weight HA shows good performances in treating RT-damaged tissue and plays a key role in all steps of the healing process . Indeed the results shows that women exposed to RT treatments and simultaneously treated with Santes ® , had an optimal resolution of vaginal atrophy and related symptoms Purpose The aim of the present study was to evaluate the effectiveness of hyaluronic acid ( HA ) in the prevention of acute and late vaginal toxicities after high-dose-rate ( HDR ) vaginal brachytherapy ( BT ) . Material and methods Between January 2011 and January 2015 , we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT + /– adjuvant chemotherapy . The total dose prescription was 21 Gy in 3 fractions ( one fraction for week ) . Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks . Acute and late toxicities were evaluated according to CTCAE vs 4.02 . Results According to the revised FIGO 2009 classification , most tumors were in stage IA ( 30.9 % ) and in stage IB ( 57.9 % ) . Thirty-three patients ( 26.2 % ) received adjuvant chemotherapy before vaginal BT . Five-year disease-free survival ( DFS ) and five-year overall survival ( OS ) were 88 % and 93 % , respectively . The most common grade 1 - 2 acute toxicities were vaginal inflammation ( 18 patients , 14.3 % ) and dyspareunia ( 7 patients , 5.5 % ) . Two patients ( 1.6 % ) had more than one toxicity . Late toxicity occurred in 20 patients ( 15.9 % ) . Grade 1 - 2 late toxicities were fibrosis ( 14 patients , 11.1 % ) and telangiectasias ( 7 patients , 5.5 % ) . Six patients ( 4.8 % ) had more than one late toxicity . No grade 3 or higher acute or late toxicities were observed . Conclusions These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery . A r and omized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity PURPOSE To compare two different fractionation schedules for postoperative vaginal high-dose-rate ( HDR ) irradiation in endometrial carcinomas . METHODS AND MATERIAL S In a complete geographic series of 290 low-risk endometrial carcinomas , the efficacy and side effects of two different fractionation schedules for postoperative vaginal irradiation were evaluated . The patients were treated during the years 1989 - 2003 . The tumors were in International Federation of Gynecology and Obstetrics Stages IA-IB and Grade s 1 - 2 . The HDR MicroSelectron afterloading equipment ( iridium-192 ) was used . Perspex vaginal applicators with diameters of 20 - 30 mm were used , and the dose was specified at 5 mm from the surface of the applicator . Six fractions were given , and the overall treatment time was 8 days . The size of the dose per fraction was r and omly set to 2.5 Gy ( total dose of 15.0 Gy ) or 5.0 Gy ( total dose of 30.0 Gy ) . One hundred forty-four patients were treated with the 2.5-Gy fraction and 146 patients with the 5.0-Gy fraction . RESULTS The overall locoregional recurrence rate of the complete series was 1.4 % and the rate of vaginal recurrences 0.7 % . There was no difference between the two r and omized groups . The vaginal shortening measured by colpometry was not significant ( p = 0.159 ) in the 2.5-Gy group ( mean , 0.3 cm ) but was highly significant ( p < 0.000001 ) in the 5.0-Gy group ( mean 2.1 cm ) after 5 years . Mucosal atrophy and bleedings were significantly more frequent in the 5.0-Gy group . Symptoms noted in the 2.5-Gy group were not different from what could be expected in a normal group of postmenopausal women . CONCLUSION The fractionation schedule recommended for postoperative vaginal irradiation in low-risk endometrial carcinoma is six fractions of 2.5 Gy when the HDR technique is used OBJECTIVE To determine the progression free survival ( PFS ) , toxicity , and patterns of failure for early stage , high-intermediate risk ( H-IR ) patients in a phase II trial with adjuvant vaginal cuff brachytherapy ( VCB ) and three cycles of carboplatin and paclitaxel . METHODS Surgically staged patients with stage I-IIb endometrial cancer with H-IR factors were treated with VCB ( 2100cGy ) followed by three cycles of carboplatin ( AUC 6 ) and paclitaxel ( 175 mg/m(2 ) ) . The primary endpoint was PFS at 2 years , with toxicity and sites of failure as secondary endpoints . Toxicity was assessed by patient report ( CTCAE v. 3 ) as well as by delays or dose modifications in treatment . RESULTS All patients completed VCB and 19/23 ( 83 % ) completed both VCB and 3 cycles of chemotherapy . Mean time to complete VCB was 14.5 days with minimal acute toxicity noted . At 6 months , all toxicity related to VCB had resolved . In total 60 cycles of chemotherapy were given , with one dose reduction ( 1.6 % ) for grade 2 neuropathy and seven delays ( 11.6 % ) in treatment due to hematologic toxicity . At a median follow-up of 44.5 months , 91 % of patients remained progression free at 2 years . Four patients experienced a recurrence ; they recurred both locally and distant . CONCLUSIONS Adjuvant therapy with VCB and chemotherapy is well tolerated in a population of patients with H-IR endometrial carcinoma and provides 2 year PFS of 91 % . A r and omized trial is currently underway to assess whether combined VCB and chemotherapy reduces the rate of recurrence compared to external beam radiation therapy ( EBRT ) in this patient population BACKGROUND AND PURPOSE Brachytherapy in the treatment of locally advanced cervical cancer has changed substantially because of the introduction of combined intracavitary/interstitial applicators and an adaptive target concept , which is the focus of the prospect i ve , multi-institutional EMBRACE study ( www.embrace study .dk ) on image-guided adaptive brachytherapy ( IGABT ) . So far , little has been reported about the development of early to late vaginal morbidity in the frame of IGABT . Therefore , the aim of the present EMBRACE analysis was to evaluate the manifestation pattern of vaginal morbidity during the first 2 years of follow-up . METHODS AND MATERIAL S In total , 588 patients with a median follow-up time of 15 months and information on vaginal morbidity were included . Morbidity was prospect ively assessed at baseline , every 3 months during the first year , and every 6 months in the second year according to the Common Terminology Criteria for Adverse Events , version 3 , regarding vaginal stenosis , dryness , mucositis , bleeding , fistula , and other symptoms . Crude incidence rates , actuarial probabilities , and prevalence rates were analyzed . RESULTS At 2 years , the actuarial probability of severe vaginal morbidity ( grade ≥3 ) was 3.6 % . However , mild and moderate vaginal symptoms were still pronounced ( grade ≥1 , 89 % ; grade ≥2 , 29 % ) , of which the majority developed within 6 months . Stenosis was most frequently observed , followed by vaginal dryness . Vaginal bleeding and mucositis were mainly mild and infrequently reported . CONCLUSION Severe vaginal morbidity within the first 2 years after definitive radiation (chemo)therapy including IGABT with intracavitary/interstitial techniques for locally advanced cervical cancer is limited and is significantly less than has been reported from earlier studies . Thus , the new adaptive target concept seems to be a safe treatment with regard to the vagina being an organ at risk . However , mild to moderate vaginal morbidity is still pronounced with currently applied IGABT , and it needs further attention PURPOSE Intravaginal high-dose-rate brachytherapy is an effective adjuvant treatment for localized endometrial carcinoma . However , relatively little is known about risk factors of post-treatment vaginal stenosis ( VS ) . METHODS AND MATERIAL S We included patients treated with brachytherapy for endometrial carcinoma from September 2011 to January 2014 with at least 3 months of followup . Patients who received external beam radiation therapy were excluded . VS was prospect ively grade d at each followup visit per Common Terminology Criteria for Adverse Events , version 4.03 . χ(2 ) and t test analyses were used to assess the association of VS with various patient , tumor , treatment , and post-treatment factors . Multivariable logistic regression analysis was used to identify independent predictors of VS Grade ≥1 and ≥2 . RESULTS All 101 patients were disease free at last followup . Mean followup was 12.9 months ( range , 3 - 34 ) . Highest VS grade s were zero in 67 % , one in 26 % , two in 6 % , and three in 1 % . Borderline significant variables associated with Grade ≥1 VS included vagina length , proportion of vagina treated , and total dose . Dilator use was significantly associated with Grade ≥2 . Multivariable analysis revealed that proportion of vagina treated > 60 % ( odds ratio [ OR ] , 3.48 ; p = 0.009 ) and total dose > 14 Gy ( OR , 4.27 ; p = 0.015 ) were independent predictors of Grade ≥1 VS , and lack of consistent dilator use was an independent predictor of Grade ≥2 VS ( OR , 5.60 ; p = 0.047 ) . CONCLUSIONS Patients treated with a higher total dose to a larger proportion of the vagina were more likely to develop Grade ≥1 VS . Consistent dilator use may also be protective against Grade ≥2 VS The aim of our study was to determine the incidence , timing , and severity of vaginal stenosis in patients with carcinoma of the cervix who had received pelvic and /or vaginal radiotherapy as part of their treatment . We also sought to determine if there were any predisposing factors for the development of stenosis . A retrospective chart review was undertaken for all the patients diagnosed with carcinoma of the cervix between January 1 , 1990 , and December 31 , 2000 and treated with pelvic and /or vaginal radiation at Westmead Hospital . Since January 1 , 1990 , data regarding vaginal stenosis has been prospect ively recorded on all the patients . Data collected included patient demographics , stage of disease , treatments administered , and incidence , timing , and severity of vaginal stenosis . One hundred and eighty-eight patients were treated . Mean age was 58.6 years . Thirteen percent of patients had stage IB disease , 45 % had stage II disease , 39.5 % had stage III disease , and 1.5 % had stage IV disease . One hundred and seventy-nine patients returned for follow-up , and data regarding vaginal toxicity were available in 98 % . Twenty-seven percent had grade 1 toxicity ( partial stenosis or shortening but not complete occlusion ) , and 11 % had grade 2 ( complete occlusion ) . Stenosis of any grade was noted at a mean of 9.6 months and median of 7.5 months ( range , 26 days-5.6 years ) from completion of treatment . The only prognostic factor associated with increased risk of stenosis was age greater than 50 years ( odds ratio 2.26 ) . Vaginal stenosis is a common complication of pelvic and vaginal radiotherapy , occurring in 38 % of patients . Stenosis occurs most often in the first year after treatment . Patients over the age of 50 are most at risk PURPOSE The value of adjuvant radiation therapy and staging pelvic lymphadenectomy in patients with low-risk , early-stage endometrial cancer is controversial . The aim of this study was to report the long-term survival , rate of recurrences , and complications in patients with Stage I endometrial cancer , Grade 1 - 2 , with < 50 % myometrial invasion treated with hysterectomy ( without formal staging pelvic and periaortic lymph node sampling or lymphadenectomy ) and postoperative vaginal brachytherapy . METHODS AND MATERIAL S A total of 303 patients with pathologic Stage I endometrial cancer , Grade 1 - 2 , with < 50 % myometrial invasion and nonmalignant peritoneal cytology , were treated with total abdominal hysterectomy , bilateral salpingo-oophorectomy , and postoperative vaginal brachytherapy ( 30 Gy to point 0.5 cm depth ) in a prospect i ve study extending from 1958 to 1994 . In addition , 29 additional Stage I , Grade 1 - 2 patients with < 50 % myometrial invasion and malignant peritoneal cytology were treated with 1 year of progesterone therapy . Patients were followed for 1.2 - 32 years ( median 8.1 y ) . RESULTS Six patients had recurrences and died secondary to disease . There were no vaginal recurrences . The 5- , 10- , 20- , and 30-year disease-free survivals of the 303 patients with nonmalignant peritoneal cytology were 98.9 % , 97.8 % , 96.7 % , and 96.7 % , respectively . Patients with malignant peritoneal cytology had a 5- and 10-year disease-free survival of 100 % . Significant radiation complications occurred in 2.1 % of the patients . CONCLUSION In patients with low-risk , Stage I endometrial cancer , hysterectomy and adjuvant postoperative vaginal brachytherapy provide excellent long-term survival , eliminate vaginal recurrences , and are not associated with significant complications . The addition of 1 year of progesterone therapy to patients with malignant cytology provides 100 % long-term survival . Based on these results , patients with low-risk , Stage I endometrial adenocarcinoma do not need formal staging pelvic and periaortic lymphadenectomy Purpose R and omized trials on the effect of external beam radiotherapy ( EBRT ) with or without vaginal brachytherapy ( VBT ) for endometrial carcinoma are very few . In view of this , the current study was conducted with the hypothesizes : whether the escalated dose of 26 Gy ( VBT alone ) in comparison with various major international trials ( PORTEC-2 ) has any difference in rates of disease-free and overall survival with fewer adverse effects in low re source setting like India . Material and methods An open-labeled , non-inferiority , r and omized control trial was undertaken at a regional cancer center among patients with stage IA or IB high-intermediate risk endometrial carcinoma . A total of 50 patients were divided equally among two arms of combined EBRT with VBT ( arm I ) and VBT alone ( arm II ) . A dose of 50 - 50.4 Gy in 25 - 28 fractions of EBRT with 2 fractions of VBT 6.5 Gy each were delivered to patients in arm I and 4 fractions of VBT 6.5 Gy each to patients in arm II , and were followed up for 60 months . Results During the median follow-up of 36.5 months , two patients developed loco-regional recurrence in arm II , three ( arm II ) , and one ( arm I ) developed distant metastasis . The 5-year survival rates for arms I and II were 96.0 % vs. 92.0 % overall , and 88.0 % vs. 84.0 % disease-free , respectively , and were not found to be statistically significantly different . Dermatological , gastro-intestinal toxicities , and cystitis were lower in the VBT group compared to combined group . Conclusions VBT alone is as effective as EBRT+VBT in ensuring loco-regional control and achieving comparable survival rates , with fewer toxic effects for patients with stage I intermediate- and high-risk endometrial carcinoma . The dose escalation did not make a difference in the survival rates and was like in the other major trials ( PORTEC-2 ) BACKGROUND After surgery for intermediate-risk endometrial carcinoma , the vagina is the most frequent site of recurrence . This study established whether vaginal brachytherapy ( VBT ) is as effective as pelvic external beam radiotherapy ( EBRT ) in prevention of vaginal recurrence , with fewer adverse effects and improved quality of life . METHODS In this open-label , non-inferiority , r and omised trial undertaken in 19 Dutch radiation oncology centres , 427 patients with stage I or IIA endometrial carcinoma with features of high-intermediate risk were r and omly assigned by a computer-generated , biased coin minimisation procedure to pelvic EBRT ( 46 Gy in 23 fractions ; n=214 ) or VBT ( 21 Gy high-dose rate in three fractions , or 30 Gy low-dose rate ; n=213 ) . All investigators were masked to the assignment of treatment group . The primary endpoint was vaginal recurrence . The predefined non-inferiority margin was an absolute difference of 6 % in vaginal recurrence . Analysis was by intention to treat , with competing risk methods . The study is registered , number IS RCT N16228756 . FINDINGS At median follow-up of 45 months ( range 18 - 78 ) , three vaginal recurrences had been diagnosed after VBT and four after EBRT . Estimated 5-year rates of vaginal recurrence were 1.8 % ( 95 % CI 0.6 - 5.9 ) for VBT and 1.6 % ( 0.5 - 4.9 ) for EBRT ( hazard ratio [ HR ] 0.78 , 95 % CI 0.17 - 3.49 ; p=0.74 ) . 5-year rates of locoregional relapse ( vaginal or pelvic recurrence , or both ) were 5.1 % ( 2.8 - 9.6 ) for VBT and 2.1 % ( 0.8 - 5.8 ) for EBRT ( HR 2.08 , 0.71 - 6.09 ; p=0.17 ) . 1.5 % ( 0.5 - 4.5 ) versus 0.5 % ( 0.1 - 3.4 ) of patients presented with isolated pelvic recurrence ( HR 3.10 , 0.32 - 29.9 ; p=0.30 ) , and rates of distant metastases were similar ( 8.3 % [ 5.1 - 13.4 ] vs 5.7 % [ 3.3 - 9.9 ] ; HR 1.32 , 0.63 - 2.74 ; p=0.46 ) . We recorded no differences in overall ( 84.8 % [ 95 % CI 79.3 - 90.3 ] vs 79.6 % [ 71.2 - 88.0 ] ; HR 1.17 , 0.69 - 1.98 ; p=0.57 ) or disease-free survival ( 82.7 % [ 76.9 - 88.6 ] vs 78.1 % [ 69.7 - 86.5 ] ; HR 1.09 , 0.66 - 1.78 ; p=0.74 ) . Rates of acute grade 1 - 2 gastrointestinal toxicity were significantly lower in the VBT group than in the EBRT group at completion of radiotherapy ( 12.6 % [ 27/215 ] vs 53.8 % [ 112/208 ] ) . INTERPRETATION VBT is effective in ensuring vaginal control , with fewer gastrointestinal toxic effects than with EBRT . VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk . FUNDING Dutch Cancer Society Abstract Purpose To analyze the vaginal-cuff local control ( VCC ) and toxicity in postoperative endometrial carcinoma patients ( EC ) underwent high-dose-rate brachytherapy ( HDR-BT ) administered daily . Material s and methods 154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011 . FIGO-staging I – IIIC2 patients were divided into two groups according to risk classification : Group 1 ( 94/154 ) included high-risk or advanced disease patients and Group 2 ( 60/154 ) included intermediate-risk EC patients . Group 1 underwent external beam irradiation ( EBI ) plus HDR-BT ( 2 fractions of 5 Gy ) and Group 2 underwent HDR-BT alone ( 4 fractions of 5 Gy ) . Toxicity evaluation was done with RTOG scores for bladder and rectum , and the objective criteria of LENT – SOMA for vagina . Results With a median follow-up of 46.7 months ( 36.6–61 months ) only two patients developed vaginal-cuff recurrence in Group 1 ( 2.1 % ) and none in group 2 ( 0 % ) . Early toxicity in Group 1 appeared 5.3 % in rectum , 7.5 % in bladder ( G1–G2 ) and 2.1 % in vagina ( G1 ) ; late toxicity was present in 7.3 % in rectum ( all G1–G2 but 1 G3 ) and in 27.7 % in vagina ( all G1–G2 but one G4 ) . In Group 2 , 6.7 % developed acute G1–G2 bladder and 6.6 % acute vaginal ( G1–G2 ) toxicity . No late rectal or bladder toxicity was observed ; 21.7 % of G1–G2 presented late problems in vagina . Conclusions The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity PURPOSE Studies on quality of life ( QOL ) among women with endometrial cancer have shown that patients who undergo pelvic radiotherapy report lower role functioning and more diarrhea and fatigue . In the Post Operative Radiation Therapy in Endometrial Cancer ( PORTEC ) trial , patients with endometrial carcinoma were r and omly assigned to receive external-beam radiotherapy ( EBRT ) or vaginal brachytherapy ( VBT ) . QOL was evaluated by using the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and subscales from the prostate cancer module , PR-25 , and the ovarian cancer module , OV-28 . PATIENTS AND METHODS PORTEC-2 accrued 427 patients between 2002 and 2006 , of whom 214 were r and omly assigned to EBRT , and 213 were r and omly assigned to VBT . Three-hundred forty-eight patients ( 81 % ) were evaluable for QOL . QOL outcomes were analyzed at a median follow-up of 2 years . Results At baseline after surgery , patient functioning was at the lowest level , and it increased during and after radiotherapy to reach a plateau after 12 months . Patients in the VBT group reported better social functioning ( P < .002 ) and lower symptom scores for diarrhea , fecal leakage , the need to stay close to the toilet , and limitation in daily activities because of bowel symptoms ( P < .001 ) . At baseline , 15 % of patients were sexually active ; this increased significantly to 39 % during the first year ( P < .001 ) . Sexual functioning and symptoms did not differ between the treatment groups . CONCLUSION Patients who received EBRT reported significantly higher levels of diarrhea and bowel symptoms . This result ed in a higher need to remain close to a toilet and , as a consequence , more limitation of daily activities because of bowel symptoms and decreased social functioning . Vaginal brachytherapy provides a better QOL , and should be the preferred treatment from a QOL perspective BACKGROUND / PURPOSE To identify risk factors for vaginal stenosis and to establish a dose-effect relationship for image-guided brachytherapy in locally advanced cervical cancer . MATERIAL S/ METHODS Patients from the ongoing EMBRACE study with prospect ively assessed morbidity ( CTCAEv3.0 ) at baseline and at least one follow-up were selected . Patient- , disease- and treatment characteristics were tested as risk factors for vaginal stenosis G ⩾ 2 in univariate and multivariable analyses ( Cox proportional hazards model ) and a dose-effect curve was deduced from the estimates . The ICRU rectum point was used to derive the recto-vaginal reference point dose . RESULTS In 630 patients included ( median follow-up 24months ) , 2-year actuarial estimate for vaginal stenosis G ⩾ 2 was 21 % . Recto-vaginal reference point dose ( HR=1.025 , p=0.029 ) , external beam radiotherapy ( EBRT ) dose > 45 Gy/25 fractions ( HR=1.770 , p=0.056 ) and tumor extension in the vagina ( HR=2.259 , p ⩽ 0.001 ) were risk factors for vaginal stenosis , adjusted for center reporting effects . Based on the model curve , the risk was 20 % at 65 Gy , 27 % at 75 Gy and 34 % at 85 Gy ( recto-vaginal reference point dose ) . CONCLUSION Keeping the EBRT dose at 45 Gy/25 fractions and decreasing the dose contribution of brachytherapy to the vagina decrease the risk of stenosis . A planning aim of ⩽65 Gy EQD2 ( EBRT+brachytherapy dose ) to the recto-vaginal reference point is therefore proposed The therapeutic use of ionizing radiations is predicated on sparing normal tissue effects while attempting to achieve lethal effects on tumor cells . From quite early in the history of radiation therapy , it was apparent that there were striking differences in effects in the panoply of normal tissues . Although there was early appreciation of some late effects in normal tissues , often not predicted by acute reactions , only in recent years has there been full documentation of the slow and progressive increase in severity of late damage . Pathophysiological mechanisms of acute and late radiation effects are better understood today ( 2 ) , but interactions of other modalities with radiation therapy require constant monitoring to recognize and mitigate untoward sequelae . The work of Stone ( 3 ) is a classic example of unanticipated late effects , which result ed from irradiation with ‘ fast neutrons . Acute reactions were moderate and tolerable , but the late sequelae were so marked that there was little interest in pursuing therapy with fast neutrons for nearly three decades . The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in fast neutron therapy and Radiation Therapy Oncology Group ( RTOG ) staff . In the late 1970s the Neutron/Particle Committee was one of several modality committees of the RTOG . Recognizing the results of Stone , this committee , led by Lawrence Davis worked with RTOG staff to establish criteria and scoring for possible late effects from fast neutron radiation therapy . Investigators from the European Organization for Research and Treatment of Cancer ( EORTC ) , led by William Duncan of the Western General Hospital of Edinburgh , wished to have common toxicity criteria in anticipation of joint studies . RTOG Protocol 7929 , an international registry of patients treated with heavy particles , was started in 1980 . At the annual meetings of the international participants in particle studies , there were attempts to monitor interobserver variations in scoring effects in normal tissues and to seek consistency in reporting toxicity , but no publications document these efforts . The first prospect i ve trial to use the Late Morbidity Scoring Criteria was RTOG Protocol 8001 , a study of fast neutron therapy for malignant tumors arising in salivary gl and s. Although the RTOG began to use these criteria in reporting toxicity in patients enrolled in all studies from 198 1 ( beginning with RTOG Protocol 8 115 ) , the criteria only became a published part of protocol s in 1983 . At that time , statistical methods began to be used , which presented time-adjusted estimates of late effects , the rationale for which was described by Cox ( 1 ) . It is now considered st and ard to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival . The Acute Radiation Morbidity Scoring Criteria were developed in 1985 as complimentary to the Late Effects Scoring Criteria . The National Cancer Institute promulgated st and ard toxicity criteria in 1990 , but late effects were not considered . An abbreviated version of the RTOG/EORTC toxicity criteria was published by Winchester and Cox in 1992 as part of the St and ard for Breast Conservation Treatment . The current RTOG Acute Radiation Morbidity Scoring Criteria are presented in Table 1 . The RTOG/EORTC Late Radiation Morbidity Scoring Scheme is detailed in Table 2 . In both tables , 0 means an absence of radiation effects and 5 means the effects led to death . The Purpose To analyze the results of daily high-dose-rate brachytherapy ( HDRBT ) on local control and toxicity in the postoperative treatment of endometrial carcinoma ( EC ) . Material s and methods From January 2007 to September 2010 , 112 patients were treated with HDRBT after surgery for EC . FIGO staging : 24-IA , 48-IB , 14-II , 12-IIIA , 2-IIIB , 8-IIIC1 and 4-IIIC2 . Pathology 99/112 endometrioid and 23/112 other types . Radiotherapy patients were divided into two groups — Group 1 ( 70/112 ) consists of external beam irradiation ( EBI ) plus HDRBT ( 2 fractions of 5–6 Gy ) and Group 2 ( 42/112 ) consists of HDRBT alone ( 4 fractions of 5–6 Gy ) . Toxicity evaluation RTOG scores for bladder and rectum , and the objective criteria of LENT-SOMA for vagina . Statistics bivariate analysis of Chi-square and Fisher exact tests . Results With a mean follow-up of 29.52 months ( range 9.60–53.57 ) no patient developed vaginal-cuff relapse . In Group 1 early toxicity appeared in 9 % in rectum , 8.5 % in bladder ( G1–G2 ) and 1.4 % in vagina ( G1 ) ; late toxicity was present in 8.5 % in rectum ( all G1–G2 but 1 G3 ) and in 25 % in vagina ( all G1–G2 but one G4 ) . In Group 2 , 9.4 % developed G1–G2 bladder and 6.9 % acute vagina ( G1–G2 ) toxicity . Only 2.3 % had a G1 rectal score and 6.9 % had G1–G2 as vaginal scores for late problems . Conclusions ( 1 ) Daily HDRBT using two fractions of 5–6 Gy after EBI and four fractions of 5–6 Gy as exclusive treatment was a safe regime . ( 2 ) Group 1 showed a higher incidence of late vaginal toxicity PURPOSE To evaluate the long-term health-related quality of life ( HRQL ) after external beam radiation therapy ( EBRT ) or vaginal brachytherapy ( VBT ) among PORTEC-2 trial patients , evaluate long-term bowel and bladder symptoms , and assess the impact of cancer on these endometrial cancer ( EC ) survivors . PATIENTS AND METHODS In the PORTEC-2 trial , 427 patients with stage I high-intermediate-risk EC were r and omly allocated to EBRT or VBT . The 7- and 10-year HRQL question naires consisted of EORTC QLQ-C30 ; subscales for bowel and bladder symptoms ; the Impact of Cancer Question naire ; and 14 questions on comorbidities , walking aids , and incontinence pads . Analysis was done using linear mixed models for subscales and ( ordinal ) logistic regression with r and om effects for single items . A two-sided P value < .01 was considered statistically significant . RESULTS Longitudinal HRQL analysis showed persisting higher rates of bowel symptoms with EBRT , without significant differences in global health or any of the functioning scales . At 7 years , clinical ly relevant fecal leakage was reported by 10.6 % in the EBRT group , versus 1.8 % for VBT ( P=.03 ) , diarrhea by 8.4 % versus 0.9 % ( P=.04 ) , limitations due to bowel symptoms by 10.5 % versus 1.8 % ( P=.001 ) , and bowel urgency by 23.3 % versus 6.6 % ( P<.001 ) . Urinary urgency was reported by 39.3 % of EBRT patients , 25.5 % for VBT , P=.05 . No difference in sexual activity was seen between treatment arms . Long-term impact of cancer scores was higher among the patients who had an EC recurrence or second cancer . CONCLUSIONS More than 7 years after treatment , EBRT patients reported more bowel symptoms with impact on daily activities , and a trend for more urinary symptoms , without impact on overall quality of life or difference in cancer survivorship issues |
10,380 | 30,653,535 | Income associated with adherence more strongly in men than women , and highly educated men were more likely and highly educated women less likely to be adherent .
Alcohol misuse and high BMI associated with non-adherence .
There was no association between polypharmacy and statin adherence .
Current evidence suggests that patients with more traditional risk factors for CVD are more likely to be adherent to statins . | INTRODUCTION Previous research has shown that statin adherence for the primary prevention of CVD is lower compared to secondary prevention population s. Therefore the aim of this systematic review was to review predictors of statin adherence for the primary prevention of CVD . | Background : Failure to adhere to medication regimes is a significant problem in clinical and research setting s yet reliable , consistent identification of key psychosocial predictors remains elusive . Studies of mood and personality related to adherence show mixed results —compliance and objective ly measured cognitive function are intuitively related but empirical support is lacking . Purpose : This study is a secondary analysis to examine the relations between adherence with a medication regime for lowering serum cholesterol and several domains of psychological and cognitive functioning . Methods : Participants in the initial study completed a measure of personality and a battery of neuropsychological measures at baseline ; anxiety and depression were measured at baseline and at 4-week intervals . Medication adherence was tracked with electronic cap monitors for 24 weeks . Results : Only 23 % of the sample was fully adherent to medication regimes at least 80 % of the time over the 6-month study period . Conscientiousness , according to the Five Factor Theory of Personality , and estimated IQ remained robust predictors of adherence in hierarchical regression analyses . Depression and anxiety , mental flexibility , and visuospatial-constructional ability were less robust but statistically significant ( p < .05 ) correlates of adherence . Conclusions : Although results of this analysis explain only a portion of the variance in adherence , they demonstrate the importance of trait psychological and cognitive factors in adherence research Background Retirement has been suggested to reduce medication adherence , but no evidence is available for statins . We investigated changes in adherence to statins among Swedish adults after retirement . Methods A prospect i ve cohort study was carried out on all individuals living in Sweden on 31 December 2004 , alive in 2010 , having purchased statins in the second half of 2005 , and retired in 2008 ( n=11 718 ) . We used prescription dispensing data in 2006–2010 to determine nonadherence ( defined as < 80 % of days covered by filled prescriptions ) before and after old-age or disability retirement . Using multiple repeat measurements of filled statin prescriptions , we calculated the annual prevalence rates of nonadherence for those who continued therapy . Discontinuation was defined as no statin dispensations during a calendar year . Results After adjustment for age at retirement , the prevalence ratio ( PR ) of nonadherence after retirement in comparison with those before retirement was 1.23 [ 95 % confidence interval ( CI ) 1.17–1.29 ] for the men and 1.19 ( 95 % CI 1.13–1.26 ) for the women . A post-retirement increase in nonadherence was consistently observed across the strata of age at retirement , marital status , education , income , type of retirement , and participants with and without cardiovascular disease , the largest increases being observed for statin use in secondary prevention ( men : PR 1.38 , 95 % CI 1.26–1.54 ; women : PR 1.43 , 1.18–1.72 ) . For primary prevention , the corresponding prevalence ratios were 1.18 ( 95 % CI 1.13‒1.25 ) and 1.18 ( 95 % CI 1.11–1.24 ) , respectively . Interpretation Retirement appears to be associated with increased nonadherence to statin therapy among Swedish men and women BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Background —Little is known about the impact of hospitalization for an acute myocardial infa rct ion ( AMI ) on subsequent adherence to statins . Methods and Results —Using administrative cl aims from a 5 % r and om sample of Medicare beneficiaries , we identified a cohort of Medicare patients aged ≥65 years , hospitalized from 2007 to 2011 , taking statins in the year before AMI hospitalization ( n=6618 ) . We then determined the proportion of patients nonadherent to statins ( proportion of days covered < 80 % ) in the year before AMI hospitalization who became statin adherent ( proportion of days covered ≥80 % ) in the year after AMI hospitalization . The proportion of statin-adherent patients who became nonadherent was also studied . These proportions were compared with patients hospitalized for pneumonia ( n=11 471 ) and patients not hospitalized ( n=158 099 ) in 2010 and 2011 . Among patients nonadherent to statins before AMI hospitalization , 37.7 % became adherent after discharge . Patients hospitalized for AMI were more likely to become adherent than patients hospitalized for pneumonia ( adjusted relative risk : 1.70 ; 95 % confidence interval , 1.57–1.84 ) or patients not hospitalized ( adjusted relative risk : 1.79 ; 95 % confidence interval , 1.68–1.90 ) . Among patients adherent to statins before AMI hospitalization , 32.6 % became nonadherent after discharge . Those hospitalized for AMI were less likely to become nonadherent than those hospitalized for pneumonia ( adjusted relative risk : 0.93 ; 95 % confidence interval 0.88–0.98 ) but more likely to become nonadherent than patients without hospitalizations ( adjusted relative risk : 1.41 ; 95 % confidence interval , 1.35–1.48 ) . Conclusions —Among nonadherent patients , hospitalization for AMI was associated with increased likelihood of becoming adherent to statins compared with hospitalization for pneumonia or no hospitalizations . Among adherent patients , hospitalization for AMI was associated with increased likelihood of becoming nonadherent to statins compared with no hospitalizations Background : Despite the importance of patients ’ adherence to their drug treatments for achieving desired therapeutic goals and the proven role 3-hydroxy-3-methylglutaryl coenzyme A inhibitors ( statins ) for the health status of patients with cardiovascular diseases , there is not enough information regarding diabetic patients ’ adherence to statin therapy in developing countries . In this clinical study we aim ed to assess the adherence of diabetes type 2 patients to statin therapy in a research based community clinic in Iran . Material s and Methods : In this prospect i ve clinical study which was done at Isfahan Endocrinology and Metabolism Research Center , 204 diabetic type 2 patients under treatment with statin were interviewed twice and their demographic data ( age , gender , body mass index , education ) , statin information ( type , dose ) and their serum lipid profile were recorded . Three months after the initial visits , patients were assessed using pill counting method and according to patients ’ self-reporting and also assessed low-density lipoprotein ( LDL ) cholesterol goal attainment < 100 mg/dl . Results : Adherence rate was 79.7 % and 69 % according to pill counting and self-reporting among study population . Moreover , 68.4 % of patients achieved their LDL cholesterol goal of < 100 mg/dl and adherent patients reached therapeutic goal significantly more than those who were considered non-adherence to statin therapy ( P < 0.01 ) . Conclusion : Adherence to statin therapy , as reflected by pill count method , is significantly related to LDL cholesterol goal achievement in patients with diabetes and dyslipidemia . Pill count method can be used to identify patients who are nonadherent to statin therapy and at high risk for failure to attain LDL cholesterol goals Background The purpose of this study was to evaluate the effectiveness of a patient education program developed to facilitate statin adherence . Methods A controlled trial was design ed to test the effectiveness of a multifaceted patient education program to facilitate statin adherence . The program included a brief , in-office physician counseling kit followed by patient mailings . The primary end point was adherence to filling statin prescriptions during a 120-day period . Patients new to statins enrolled and completed a survey . Data from a national pharmacy cl aims data base were used to track adherence . Results Patients new to statin therapy exposed to a patient counseling and education program achieved a 12.4 higher average number of statin prescription fill days and were 10 % more likely to fill prescriptions for at least 120 days ( p = .01 ) . Conclusion Brief in-office counseling on cardiovascular risk followed by patient education mailings can be effective in increasing adherence . Physicians found a one-minute counseling tool and pocket guidelines useful in counseling patients 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 BACKGROUND Adherence to statins in real-world practice setting s is known to be suboptimal . However , less is known about how adherence changes over time and whether changes in adherence are associated with adverse cardiovascular ( CV ) outcomes . OBJECTIVES To ( a ) characterize yearly changes in adherence among initially adherent patients taking statins for primary prevention and ( b ) assess the association between changes in statin adherence with subsequent risk of CV events . METHODS A 10 % r and om sample of the IMS LifeLink Health Plan Cl aims Data base covering the time period from July 1 , 1997 , to December 31 , 2008 , was used to identify a cohort of primary prevention statin users . Adherence was estimated in yearly segments beginning with the index statin prescription using proportion of days covered ( PDC ) . PDC was categorized into 3 levels : PDC ≥ 0.80 , 0.20 ≤ PDC < 0.80 , PDC < 0.20 . Patients were excluded if they experienced CV events or had PDC < 0.80 in their first year of statin exposure . Descriptive statistics were used to explore proportions of the cohort in each PDC category during each year . Cox-proportional hazards models were used to estimate the 5-year CV event risk associated with yearly adherence transitions . RESULTS Of the 11,126 patients beginning at the highest level of adherence ( PDC ≥ 0.80 ) in year 1 , 70 % remained at this level in year 2 . Of those in this level during year 2 , 73 % remained at this level in year 3 . 828 ( 7.44 % ) experienced a CV event during their observable follow-up time . It was found that those who transitioned from the highest to the lowest level of adherence in year 2 ( PDC < 0.20 ) experienced 2.26 greater CV event hazard ( P < 0.0001 ) . Adjusting for year 2 adherence , patients at the lowest level in year 3 experienced a 271 % increase in CV hazard ( P < 0.0001 ) , as compared with the highest level of adherence . CONCLUSION This study found that patients ' adherence levels tend to decline over time , and a transition to levels of adherence lower than a PDC of 80 % was associated with increased risk of CV events . These results are useful in the context of targeting interventions that aim to improve patients ' adherence Objectives To develop and vali date up date d QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors . Design Prospect i ve open cohort study . Setting General practice s in Engl and providing data for the Q Research data base . Participants 1309 Q Research general practice s in Engl and : 981 practice s were used to develop the scores and a separate set of 328 practice s were used to vali date the scores . 7.89 million patients aged 25 - 84 years were in the derivation cohort and 2.67 million patients in the validation cohort . Patients were free of cardiovascular disease and not prescribed statins at baseline . Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years . Risk factors considered included those already in QRISK2 ( age , ethnicity , deprivation , systolic blood pressure , body mass index , total cholesterol : high density lipoprotein cholesterol ratio , smoking , family history of coronary heart disease in a first degree relative aged less than 60 years , type 1 diabetes , type 2 diabetes , treated hypertension , rheumatoid arthritis , atrial fibrillation , chronic kidney disease ( stage 4 or 5 ) ) and new risk factors ( chronic kidney disease ( stage 3 , 4 , or 5 ) , a measure of systolic blood pressure variability ( st and ard deviation of repeated measures ) , migraine , corticosteroids , systemic lupus erythematosus ( SLE ) , atypical antipsychotics , severe mental illness , and HIV/AIDs ) . We also considered erectile dysfunction diagnosis or treatment in men . Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group , ethnicity , and baseline disease status . Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources : general practice , mortality , or hospital admission records . Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation . All new risk factors considered met the model inclusion criteria except for HIV/AIDS , which was not statistically significant . The models had good calibration and high levels of explained variation and discrimination . In women , the algorithm explained 59.6 % of the variation in time to diagnosis of cardiovascular disease ( R2 , with higher values indicating more variation ) , and the D statistic was 2.48 and Harrell ’s C statistic was 0.88 ( both measures of discrimination , with higher values indicating better discrimination ) . The corresponding values for men were 54.8 % , 2.26 , and 0.86 . Overall performance of the up date d QRISK3 algorithms was similar to the QRISK2 algorithms . Conclusion Up date d QRISK3 risk prediction models were developed and vali date d. The inclusion of additional clinical variables in QRISK3 ( chronic kidney disease , a measure of systolic blood pressure variability ( st and ard deviation of repeated measures ) , migraine , corticosteroids , SLE , atypical antipsychotics , severe mental illness , and erectile dysfunction ) can help enable doctors to identify those at most risk of heart disease and stroke Purpose Statins are potent drugs for reducing cholesterol and cardiovascular disease ; however , their effectiveness is significantly compromised by poor adherence . This prospect i ve study was design ed to identify potentially modifiable patient factors including medication , disease , and diet beliefs related to statin adherence . Methods Veterans ( n = 71 ) given their first prescription of a statin for primary prevention were interviewed at baseline , 3 months , and 6 months regarding medication , disease , and diet beliefs along with self-reported statin adherence . Results At 6-month follow-up , 55 % of the cohort was non-adherent with 10 % reporting never having started their statin , 50 % reporting misconceptions about the duration of treatment and a median use of < 2 months among those who discontinued their statin . Multivariate predictors of non-adherence were expected short treatment duration ( OR = 3.6 , 1.4–9.4 ) , low perceived risk of myocardial infa rct ion ( OR = 3.1 , 1.1–8.7 ) , concern about potential harm from statins ( OR = 2.5 , 1.0–6.3 ) , being Hispanic ( OR = 3.9 , 1.0–15.2 ) , and younger age ( OR = 4.2 , 1.1–15.8 ) . Conclusions Poor adherence to statins was common in this primary prevention population with frequent early discontinuation despite access to low-cost medicines . Patient factors regarding the perception of risk , toxic effects of medication , expected treatment duration , as well as socio-demographic factors , were significant predictors of poor adherence and warrant further exploration BACKGROUND Noncompliance with cardiovascular therapy and prevention initiatives is well documented . OBJECTIVES The purpose of the First Myocardial Infa rct ion ( MI ) Risk Reduction Program , an open-label drug registry involving mainly primary -care patients at increased risk of a first MI , was to examine the effects of postal and telephone reminders , as well as demographic and other baseline characteristics , on patient self-reported compliance with pravastatin treatment . A second objective was to determine whether regimen adherence was associated with the adoption of other lifestyle modifications recommended to decrease the risk of coronary artery disease . METHODS Patients with risk scores of > or = 4 on a scale of -1 to + 16 for men and -1 to + 17 for women on the First Heart Attack Risk Test were considered to be at increased risk of a first MI and eligible for enrollment in the registry program . An elevated total cholesterol level despite dietary interventions was an additional inclusion criterion . Patients were prospect ively r and omized ( 4:1 ) to either an intervention involving postal and telephone reminders ( about coronary risk reduction and medication compliance ) , which were sent during the first 2 months of pravastatin treatment , or usual care . Both groups received reminder postcards at 4 and 5 months , in addition to counseling by physicians about coronary risk reduction . At 3 and 6 months ( or study discontinuation ) , patients completed and mailed to the program-coordinating center question naires concerning compliance with care , including current use of prescribed pravastatin , as well as self-reported adoption of other lifestyle modifications , such as changing eating habits , losing weight , increasing physical activity , and /or quitting smoking . Compliance with pravastatin therapy and with these coronary risk-reducing behaviors was also assessed by physicians at the 3-month follow-up visit . RESULTS A total of 10,335 patients were in the intervention group , and 2765 received usual care . The 2 groups were well balanced at baseline with respect to age , race , and total cholesterol values . Neither early reminders nor baseline patient characteristics were significantly associated with reported pravastatin compliance rates , which were approximately 79 % overall . However , according to self-reports at 6 months , regimen compliance was associated with the adoption of other coronary risk-reducing behaviors . CONCLUSIONS The results of this study suggest that early telephone and postal reminders do not improve compliance with drug treatment or with recommended coronary risk-reducing behaviors ABSTRACT Background Medication nonadherence is an important obstacle to cardiovascular disease management . Objective To improve adherence through real-time feedback based on theories of how social forces influence behavior . Design Two r and omized controlled pilot trials called PROMOTE and SUPPORT . Participants stored statin medication in wireless-enabled pill bottles that transmitted adherence data to research ers . Participants Adults with diabetes and a history of low statin adherence based on pharmacy refills ( i.e. , Medication Possession Ratio [ MPR ] < 80 % in the pre-r and omization screening period).InterventionIn PROMOTE , each participant was r and omized to 1 ) weekly messages in which that participant ’s statin adherence was compared to that of other participants ( comparison ) , 2 ) weekly summaries of that participant ’s statin adherence ( summary ) , or 3 ) control . In SUPPORT , each participant identified another person ( the Medication Adherence Partner [ MAP ] ) to receive reports about that participant ’s adherence , and was r and omized to 1 ) daily reports to MAP , 2 ) weekly reports to MAP , 3 ) reports to MAP only if dose was missed , or 4 ) control . Main Outcomes MeasureAdherence measured by pill bottle . Key Results Among 45,000 health plan members contacted by mail , < 1 % joined the trial . Participants had low baseline MPRs ( median = 60 % , IQR 41–72 % ) but high pill-bottle adherence ( 90 % in PROMOTE , 92 % in SUPPORT ) during the trial . In PROMOTE ( n = 201 ) and SUPPORT ( n = 200 ) , no intervention demonstrated significantly better adherence vs. control . In a subgroup of PROMOTE participants with the lowest pre- study MPR , pill-bottle-measured adherence in the comparison arm ( 89 % ) was higher than the control ( 86 % ) and summary ( 76 % ) arms , but differences were non-significant ( p = 0.10 ) . Conclusions Interventions based on social forces did not improve medication adherence vs. control over a 3-month period . Given the low percentage of invited individuals who enrolled , the studies may have attracted participants who required little encouragement to improve adherence other than study participation Background Statins reduce cardiovascular morbidity and mortality after continuous treatment . Studies have shown that less than 50 % of patients take 80 % or more of prescribed doses 1 year after starting therapy . Objective To evaluate the impact of statin adherence on the incidence of coronary artery disease ( CAD ) . Methods A cohort of 115,290 patients was reconstructed using the Régie de l’assurance maladie du Québec data bases . Patients aged 45 to 85 years , without indication of cardiovascular disease ( CVD ) , and newly treated with statins between 1999 and 2004 were eligible . A nested case-control design was used to study CAD . Every case was matched for age and duration of follow-up with r and omly selected controls . The adherence level was measured by calculating the medication possession ratio . Rate ratios ( RR ) of CAD were determined through conditional logistic regression adjusted for several covariates . Results The mean patient age was 63 years , 54 % had hypertension , 26 % had diabetes , and 41 % were males . The proportion of patients with high adherence level to statins ( ≥ 80 % ) was 74 % during the first year and 53 % after 1 year of follow-up . High adherence was associated with a risk reduction of 18 % [ RR : 0.82 ( 95 % CI : 0.77 - 0.87 ) ] compared to an adherence level of < 20 % . Developing a CVD during follow-up , being male , having been diagnosed with hypertension or diabetes , or having a high chronic disease score increased the risk of CAD . Conclusion Our study suggests that better adherence to statin agents is associated with a significant risk reduction of CAD . Adherence to statin agents needs to be improved so that patients can benefit from the full protective effects of statin therapies BACKGROUND Many patients lack motivation to control cardiovascular risk factors and clinicians have long sought ways to activate apathetic patients . Despite significant and consistent data on the benefits of lipid-lowering agents to reduce cardiovascular events , adherence and utilization of these agents remains low . We evaluated whether visualization of coronary calcium would positively affect patients ' adherence rates . METHODS We evaluated patients who underwent electron beam tomography ( EBT ) coronary calcium evaluation at least 1 year prior with a survey question ing them about health behaviors . Patients filled out baseline and follow-up question naires relating to lifestyle modifications , including statin utilization , diet , exercise , tobacco cessation and vitamin/antioxidant utilization . RESULTS The study population consisted of 505 individuals on statin therapy on baseline who were followed for a mean of 3 + /- 2 years . Overall the statin compliance was lowest ( 44 % ) among those with CAC score in the first quartile ( 0 - 30 ) , whereas 91 % of individuals with baseline CAC score in the fourth quartile ( > or= 526 ) adhered to statin therapy . In multivariable analysis , after adjusting for cardiovascular risk factors , age , and gender , higher baseline CAC scores were strongly associated with adherence to statin therapy . CONCLUSIONS In addition to risk stratification for the asymptomatic person , patients visualizing coronary artery calcium may improve utilization and adherence to lipid-lowering therapy . Outcome studies and r and omized trials need to be done to quantify the true value and cost-effectiveness of this approach OBJECTIVES To identify self-reported reasons for not filling a new prescription for statin therapy . STUDY DESIGN A cross-sectional telephone survey . METHODS Potential participants were identified from a r and omized , controlled trial among Kaiser Permanente Southern California ( KPSC ) members aged > 24 years with no record of redeeming a new statin medication , defined as primary nonadherence . Among 1158 eligible patients , 98 were r and omly selected and participated in a semi-structured telephone interview that included questions on whether the respondent redeemed their statin prescription , why the patient may have chosen not to use a KPSC pharmacy , reasons for not filling the prescription , use of non-prescription products for elevated cholesterol levels , and questions to assess health literacy . RESULTS At 12 weeks post-index prescription date , 75 % of 98 respondents reported not filling their new statin prescription , 20 % reported picking it up from a non-KPSC pharmacy , 4 % had already picked up the prescription at a KPSC pharmacy , and 1 % did not know if it had been filled . The 3 most commonly cited reasons for primary nonadherence were general concerns about taking the medication ( 63 % ) , a decision to try lifestyle modifications ( 63 % ) , and fear of side effects ( 53 % ) . A substantial proportion ( 33 % ) of respondents reported inadequate health literacy . CONCLUSIONS These data suggest the need for interventions that address patients ' negative perceptions of statins while emphasizing the benefits of statin therapy for reducing cardiovascular morbidity and mortality in formats accessible to those with limited health literacy The basic objective of this paper is to evaluate an age-comorbidity index in a cohort of patients who were originally enrolled in a prospect i ve study to identify risk factors for peri-operative complications . Two-hundred and twenty-six patients were enrolled in the study . The participants were patients with hypertension or diabetes who underwent elective surgery between 1982 and 1985 and who survived to discharge . Two-hundred and eighteen patients survived until discharge . These patients were followed for at least five years post-operatively . The estimated relative risk of death for each comorbidity rank was 1.4 and for each decade of age was 1.4 . When age and comorbidity were modelled as a combined age-comorbidity score , the estimated relative risk for each combined age-comorbidity unit was 1.45 . Thus , the estimated relative risk of death from an increase of one in the comorbidity score proved approximately equal to that from an additional decade of age . The combined age-comorbidity score may be useful in some longitudinal studies to estimate relative risk of death from prognostic clinical covariates Using population -based automated pharmacy data , patterns of use of selected prescription medications during a 1 year time period identified by a consensus judgement process were used to construct a measure of chronic disease status ( Chronic Disease Score ) . This score was evaluated in terms of its stability over time and its association with other health status measures . In a pilot test sample of high utilizers of ambulatory health care well known to their physicians ( n = 219 ) , Chronic Disease Score ( CDS ) was correlated with physician ratings of physical disease severity ( r = 0.57 ) . In a second r and om sample of patients ( n = 722 ) , its correlation with physician-rated disease severity was 0.46 . In a total population analysis ( n = 122,911 ) , it was found to predict hospitalization and mortality in the following year after controlling for age , gender and health care visits . In a population sample ( n = 790 ) , CDS showed high year to year stability ( r = 0.74 ) . Based on health survey data , CDS showed a moderate association with self rated health status and self reported disability . Unlike self-rated health status and health care utilization , CDS was not associated with depression or anxiety . We conclude that scoring automated pharmacy data can provide a stable measure of chronic disease status that , after controlling for health care utilization , is associated with physician-rated disease severity , patient-rated health status , and predicts subsequent mortality and hospitalization rates . Specific methods of scoring automated pharmacy data to measure global chronic disease status may require adaptation to local prescribing practice s. Scoring might be improved by empirical estimation of weighting factors to optimize prediction of mortality and other health status measures Context Is alcohol misuse associated with medication nonadherence ? Contribution This study of primary care patients attending 7 Veterans Affairs clinics found a grade d , linear decrease in adherence to statins and hypertension medications with increasing levels of alcohol misuse . Caution Alcohol misuse was measured with a brief screening question naire that was mailed to patients . Adherence was measured by pharmacy refills . Implication Alcohol misuse may be associated with increased risk for medication nonadherence . The Editors Daily medications are the cornerstone of chronic disease management . Medications to treat hypertension , hyperlipidemia , and diabetespotent risk factors for cardiovascular diseaseare common and are often prescribed for asymptomatic patients to prevent future disease . However , nonadherence to medications is common ( 1 ) and is associated with poor outcomes , increased health care costs ( 2 , 3 ) , and death ( 4 ) . Many studies have examined patient characteristics associated with nonadherence , but most identified risk factors for nonadherence are not modifiable . Alcohol misuse is common , has been associated with medication nonadherence , and is modifiable ( 57 ) . However , research on alcohol misuse and medication adherence has been largely limited to patients with HIV ( 811 ) and a few studies of diabetes ( 3 , 12 , 13 ) . One recent study found both a temporal and a doseresponse relationship between alcohol consumption and medication adherence ( 8) but used a lengthy interview measure of alcohol use that is not practical for busy clinical setting s. Therefore , it remains unclear whether brief vali date d alcohol screening question naires used in clinical practice could identify patients at risk for nonadherence due to alcohol misuse . We examined whether primary care outpatient scores on a brief , scaled , alcohol screening question nairethe Alcohol Use Disorder Identification TestConsumption (AUDIT-C)were associated with medication nonadherence . Specifically , we evaluated the association between increasing scores on the AUDIT-C ( score range , 0 to 12 ) and adherence to oral medications commonly used for hypertension , hyperlipidemia , and diabetes . We hypothesized that higher AUDIT-C scores would be associated with an increased risk for medication nonadherence . Methods Participants and Setting We used data collected from the Ambulatory Care Quality Improvement Project ( ACQUIP ) cohort in this study ( 14 ) . In brief , ACQUIP enrolled 36821 active patients from the general internal medicine clinics of 7 Veterans Affairs ( VA ) medical centers nationwide , including facilities in Seattle , Washington ; West Los Angeles , California ; Birmingham , Alabama ; Little Rock , Arkansas ; San Francisco , California ; Richmond , Virginia ; and White River Junction , Vermont . The ACQUIP initially surveyed all VA sites and selected these 7 sites ( from 60 respondents ) on the basis of geographic diversity ; well-established systems for assigning patients to firms ; and an experienced , interested investigator to lead the study . The ACQUIP was a r and omized trial testing the effect of an audit and feedback quality -improvement intervention ; there was no detectable effect of the intervention on primary outcomes , including alcohol misuse ( 14 ) . Patients were eligible for ACQUIP if they had at least 1 visit to a primary care facility in the past year and had a primary care provider . The ACQUIP sent question naires ( ACQUIP Health Checklist ) at enrollment ( 1997 to 2000 ) , and the institutional review board considered participant response to the survey to be consent for study participation . The survey assessed demographic characteristics , alcohol misuse , other health behaviors , and psychiatric and medical conditions . Patients who did not respond were mailed up to 3 additional surveys . The date the survey was received by the study team was considered the index date for all participants . Survey data were linked to electronic records , including pharmacy , diagnosis , and death records . Participants who died during follow-up were excluded . The institutional review board at each participating VA site approved ACQUIP , and the University of Washington Division of Human Subjects approved the secondary analyses that we present in this article . Pharmacy Data and Medication Cohorts Pharmacy data were retrieved electronically as part of the ACQUIP protocol from December 1995 to May 2000 . Each prescription filled generated 1 record containing the drug name , the quantity and date dispensed , and the number of days supplied . These data are nearly identical to national VA pharmacy data ( 15 ) , which have been used in several studies of medication adherence and pharmacoepidemiology ( 16 , 17 ) . We identified 3 nonexclusive cohorts of patients with increasing medication regimen complexity : a statin cohort , consisting of all patients prescribed a statin medication for hypercholesterolemia ; an oral hypoglycemic cohort , with all patients who were prescribed either a sulfonylurea or metformin for blood glucose control ; and a hypertension treatment cohort , consisting of all patients with self-reported hypertension who were prescribed at least 1 of 6 classes of antihypertensive drugs ( -blockers , angiotensin-converting enzyme inhibitors , -blockers , calcium-channel blockers , thiazide-type diuretics , or nonthiazide diuretics ) and a group consisting of other antihypertension medications usually used as fourth- or fifth-line agents ( such as hydralazine ) . We considered patients medication users and included them in 1 of the cohorts if they received both 1 or more fills of the drug class within 2 years before the index date and 1 or more fills in the year after the index date . We used these criteria to minimize potential dropout bias by ensuring that patients were still engaged in care and obtaining medications from the VA . We excluded glitazones and angiotensin-receptor blockers from analyses because few patients were prescribed these medications , which were on a restricted formulary at the time of the study . In addition , we excluded patients in the oral hypoglycemic cohort if they had an active prescription for insulin other than neutral protamine Hagedorn , in order to remove patients who transitioned from oral medication to insulin during the study . Alcohol Misuse and AUDIT-C We assessed alcohol misuse with the AUDIT-C from the ACQUIP Health Checklist . The AUDIT-C assesses frequency and typical quantity of drinking during the past year , as well as the frequency of heavy episodic drinking ( 6 drinks per occasion ) by using 3 questions ( 18 ) . Each of the 3 questions is scored 0 to 4 , for a total combined score of 0 to 12 . The AUDIT-C is reliable ( 19 ) and has been vali date d as a screening test for the spectrum of alcohol misuse , including risky drinking and alcohol-use disorders on the basis of Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria ( 18 , 20 , 21 ) . A score of 4 or more is considered positive for alcohol misuse in male VA patients , but the AUDIT-C score has also been shown to be a scaled measure of risk for alcohol-related symptoms ( 22 ) and medical complications often associated with alcohol misuse ( 2326 ) . To provide adequate precision in estimates and allow comparison with previous analyses ( 23 , 24 ) , we grouped AUDIT-C scores into 5 categories : nondrinkers ( score , 0 ) ; low-level alcohol use ( score range , 1 to 3 ) ; and mild ( score range , 4 to 5 ) , moderate ( score range , 6 to 7 ) , and severe ( score range , 8 to 12 ) alcohol misuse . Medication Adherence We created an individual measure of refill adherence , which was previously vali date d within the VA and ACQUIP , for each patient and medication class . This measure is similar to a medicationpossession ratio , and it accounts for overstocking and medication gaps , correlates better with physiologic outcomes when compared with previous measures , and is described in detail elsewhere ( 27 ) . From this measure , we derived a proportion of days covered that reflected the number of days during the observation period that medication was available ( 17 ) . We considered all medications within a medication type ( statin , oral hypoglycemics , and antihypertensive medications ) to be equivalent for purpose s of adherence . We calculated adherence separately for 2 different periods : 90 days and 1 year starting from the index date . We assessed at 1 year because it is a traditional measurement of adherence ( 16 , 17 ) . We also assessed at 90 days because refill adherence for this period has been correlated with outcomes ( 27 ) . On the basis of previous medication adherence literature ( 16 , 17 ) , we considered patients in all medication cohorts to be adherent if they had medication available for at least 80 % of the observation period . In other words , for the 90-day observation period , nonadherent patients would not have medication available for at least 18 days ; for the 1 year-period , they would be without medication for at least 73 days . When more than 1 medication was used ( for example , for diabetes or hypertension ) , the proportions of days covered were averaged , and we considered patients to be adherent if they had at least 80 % of the drug regimen for diabetes or hypertension available for the observation period . A person who met the definition of a user for 2 drug classes but only maintained complete fills of 1 drug with no fills of the other drug therefore would have an average adherence of 0.5 and would be considered nonadherent to the overall regimen . Covariates Race was based on a combination of self-report from the ACQUIP Health Checklist and the electronic record . We determined sex , education , and marital status from the ACQUIP Health Checklist . We calculated a drug count from the number of oral drugs that patients obtained during the year before the index date to adjust for total medication regimen complexity . We classified smoking status as current , former , or never . We assessed depression with the Mental Health Inventory ( score range , 5 to 30 ) ; scores |
10,381 | 32,198,298 | Subgroup analyses suggested that the risk for total and ischaemic stroke was significantly decreased in females , participants with ≥25 mg/m2 body mass index and those with ≥12-year follow-up ; the reduced risk in Asians was not as notable as that in North American and European population s. CONCLUSIONS Magnesium intake has significantly inverse associations with T2D and total stroke in a dose-dependent manner . | OBJECTIVE The detailed associations between type 2 diabetes ( T2D ) and total stroke and magnesium intake as well as the dose-response trend should be up date d in a timely manner . | BACKGROUND AND PURPOSE High intakes of calcium , potassium , and magnesium have been hypothesized to reduce risks of cardiovascular disease , but only a few prospect i ve studies have examined intakes of these cations in relation to risk of stroke . METHODS In 1980 , 85 764 women in the Nurses ' Health Study cohort , aged 34 to 59 years and free of diagnosed cardiovascular disease and cancer , completed dietary question naires from which we calculated intakes of calcium , potassium , and magnesium . By 1994 , after 1.16 million person-years of follow-up , 690 incident strokes ( 129 subarachnoid hemorrhages , 74 intraparenchymal hemorrhages , 386 ischemic strokes , and 101 strokes of undetermined type ) had been documented . RESULTS Intakes of calcium , potassium , and magnesium were each inversely associated with age- and smoking-adjusted relative risks of ischemic stroke , excluding embolic infa rct ion of nonatherogenic origin ( n=347 ) . Adjustment for other cardiovascular risk factors , including history of hypertension , attenuated these associations , particularly for magnesium intake . In a multivariate analysis , women in the highest quintile of calcium intake had an adjusted relative risk of ischemic stroke of 0.69 ( 95 % CI , 0.50 to 0.95 ; P for trend=0.03 ) compared with those in the lowest quintile ; for potassium intake the corresponding relative risk was 0.72 ( 95 % CI , 0.51 to 1.01 ; P for trend=0.10 ) . Further simultaneous adjustment for calcium and potassium intake suggested an independent association for calcium intake . The association of risk with calcium intake did not appear to be log linear ; the increase in risk was limited to the lowest quintile of intake , and intakes > approximately 600 mg/d did not appear to reduce risk of stroke further . The inverse association with calcium intake was stronger for dairy than for nondairy calcium intake . Intakes of calcium , potassium , and magnesium were not related to risk of other stroke subtypes . CONCLUSIONS Low calcium intake , and perhaps low potassium intake , may contribute to increased risk of ischemic stroke in middle-aged American women . It remains possible that women in the lowest quintile of calcium intake had unknown characteristics that made them susceptible to ischemic stroke Background and Purpose The etiology of ischemic stroke affects prognosis , outcome , and management . Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke . A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) . Methods A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies . “ Possible ” and “ probable ” diagnoses can be made based on the physician 's certainty of diagnosis . The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria . The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients , first based only on clinical features and then after review ing the results of diagnostic tests . Results The TOAST classification denotes five subtypes of ischemic stroke : 1 ) large-artery atherosclerosis , 2 ) cardioembolism , 3 ) small-vessel occlusion , 4 ) stroke of other determined etiology , and 5 ) stroke of undetermined etiology . Using this rating system , interphysician agreement was very high . The two physicians disagreed in only one patient . They were both able to reach a specific etiologic diagnosis in 11 patients , whereas the cause of stroke was not determined in nine . Conclusions The TOAST stroke subtype classification system is easy to use and has good interobserver agreement . This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke . Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke OBJECTIVE To examine associations between type 2 diabetes and fiber , glycemic load ( GL ) , dietary glycemic index ( GI ) , and fiber-rich foods . RESEARCH DESIGN AND METHODS This was a prospect i ve study of 36,787 men and women aged 40 - 69 years without diabetes . For all self-reported cases of diabetes at 4-year follow-up , confirmation of diagnosis was sought from medical practitioners . Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes . Data were analyzed with logistic regression , adjusting for country of birth , physical activity , family history of diabetes , alcohol and energy intake , education , 5-year weight change , sex , and age . RESULTS Follow-up was completed by 31,641 ( 86 % ) participants , and 365 cases were identified . The odds ratio ( OR ) for the highest quartile of white bread intake compared with the lowest was 1.37 ( 95 % CI 1.04 - 1.81 ; P for trend = 0.001 ) . Intakes of carbohydrate ( OR per 200 g/day 0.58 , 0.36 - 0.95 ) , sugars ( OR per 100 g/day 0.61 , 0.47 - 0.79 ) , and magnesium ( OR per 500 mg/day 0.62 , 0.43 - 0.90 ) were inversely associated with incidence of diabetes , whereas intake of starch ( OR per 100 g/day 1.47 , 1.06 - 2.05 ) and dietary GI ( OR per 10 units 1.32 , 1.05 - 1.66 ) were positively associated with diabetes . These relationships were attenuated after adjustment for BMI and waist-to-hip ratio . CONCLUSIONS Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes . One way to achieve this would be to substitute white bread with low-GI breads This study assessed the hypothesis that greater magnesium intake is associated with reduced risk for cardiovascular disease ( CVD ) , including myocardial infa rct ion ( MI ) and stroke , in a large prospect i ve cohort of women . In 1993 , a semi-quantitative food frequency question naire was used to assess magnesium intake in 39,876 female health professionals aged 39 to 89 years who had no history of CVD or cancer . During a median of 10 years of follow-up , 1,037 incident cases of CVD were identified , including 280 nonfatal MIs and 368 strokes . After adjustment for age and r and omized treatment status , magnesium intake was not significantly associated with risk for incident CVD . Comparing the highest quintile of magnesium intake ( median 433 mg/day ) with the lowest quintile ( median 255 mg/day ) , the relative risks were 0.87 ( 95 % confidence interval [ CI ] 0.72 to 1.05 , p for trend = 0.24 ) for total CVD , 0.88 ( 95 % CI 0.70 to 1.12 , p for trend = 0.34 ) for coronary heart disease ( CHD ) , 1.03 ( 95 % CI 0.72 to 1.49 , p for trend = 0.96 ) for nonfatal MI , 1.11 ( 95 % CI 0.61 to 2.00 , p for trend = 0.95 ) for CVD death , and 0.87 ( 95 % CI 0.64 to 1.18 , p for trend = 0.55 ) for total stroke . Additional adjustment for other CVD risk factors did not material ly change the observed null associations . In conclusion , the results do not support the hypothesis that magnesium intake reduces the development of CHD , although a modest inverse association with stroke can not be ruled out Purpose Observational studies have reported increased colon cancer recurrence and mortality in patients with states of hyperinsulinemia , including type 2 diabetes , obesity , sedentary lifestyle , and high glycemic load diet . Nut intake has been associated with a lower risk of type 2 diabetes , metabolic syndrome , and insulin resistance . However , the effect of nut intake on colon cancer recurrence and survival is not known . Patients and Methods We conducted a prospect i ve , observational study of 826 eligible patients with stage III colon cancer who reported dietary intake on food frequency question naires while enrolled onto a r and omized adjuvant chemotherapy trial . Using Cox proportional hazards regression , we assessed associations of nut intake with cancer recurrence and mortality . Results After a median follow-up of 6.5 years , compared with patients who abstained from nuts , individuals who consumed two or more servings of nuts per week experienced an adjusted hazard ratio ( HR ) for disease-free survival of 0.58 ( 95 % CI , 0.37 to 0.92 ; Ptrend = .03 ) and an HR for overall survival of 0.43 ( 95 % CI , 0.25 to 0.74 ; Ptrend = .01 ) . In subgroup analysis , the apparent benefit was confined to tree nut intake ( HR for disease-free survival , 0.54 ; 95 % CI , 0.34 to 0.85 ; Ptrend = .04 ; and HR for overall survival , 0.47 ; 95 % CI , 0.27 to 0.82 ; Ptrend = .04 ) . The association of total nut intake with improved outcomes was maintained across other known or suspected risk factors for cancer recurrence and mortality . Conclusion Diets with a higher consumption of nuts may be associated with a significantly reduced incidence of cancer recurrence and death in patients with stage III colon cancer BACKGROUND Dietary carbohydrates may influence the development of type 2 ( non-insulin-dependent ) diabetes , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women Microbial modulation of diabetes Short-chain fatty acids ( SCFAs ) are produced by various human gut microbes . SCFAs act as an energy source to the colonic epithelium and are also sensed by host signaling pathways that modulate appetite and inflammation . Deficiency of gut SCFAs is associated with type 2 diabetes . Zhao et al. found that adopting a high-fiber diet promoted the growth of SCFA-producing organisms in diabetic humans . The high-fiber diet induced changes in the entire gut microbe community and correlated with elevated levels of glucagon-like peptide-1 , a decline in acetylated hemoglobin levels , and improved blood-glucose regulation . Science , this issue p. 1151 Increasing dietary fiber intake increases the abundance of short-chain fatty acid – producing gut microbes and relieves diabetes . The gut microbiota benefits humans via short-chain fatty acid ( SCFA ) production from carbohydrate fermentation , and deficiency in SCFA production is associated with type 2 diabetes mellitus ( T2DM ) . We conducted a r and omized clinical study of specifically design ed isoenergetic diets , together with fecal shotgun metagenomics , to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM . When the fiber-promoted SCFA producers were present in greater diversity and abundance , participants had better improvement in hemoglobin A1c levels , partly via increased glucagon-like peptide-1 production . Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide . Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM OBJECTIVE To investigate the long-term associations of magnesium intake with incidence of diabetes , systemic inflammation , and insulin resistance among young American adults . RESEARCH DESIGN AND METHODS A total of 4,497 Americans , aged 18–30 years , who had no diabetes at baseline , were prospect ively examined for incident diabetes based on quintiles of magnesium intake . We also investigated the associations between magnesium intake and inflammatory markers , i.e. , high-sensitivity C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) , and fibrinogen , and the homeostasis model assessment of insulin resistance ( HOMA-IR ) . RESULTS During the 20-year follow-up , 330 incident cases of diabetes were identified . Magnesium intake was inversely associated with incidence of diabetes after adjustment for potential confounders . The multivariable-adjusted hazard ratio of diabetes for participants in the highest quintile of magnesium intake was 0.53 ( 95 % CI , 0.32–0.86 ; Ptrend < 0.01 ) compared with those in the lowest quintile . Consistently , magnesium intake was significantly inversely associated with hs-CRP , IL-6 , fibrinogen , and HOMA-IR , and serum magnesium levels were inversely correlated with hs-CRP and HOMA-IR . CONCLUSIONS Magnesium intake was inversely longitudinally associated with incidence of diabetes in young American adults . This inverse association may be explained , at least in part , by the inverse correlations of magnesium intake with systemic inflammation and insulin resistance Background Intakes of magnesium , potassium , and calcium have been inversely associated with the incidence of hypertension , a known risk factor for stroke . However , only a few studies have examined intakes of these cations in relation to risk of stroke . Aim The aim of this study was to investigate whether high intake of magnesium , potassium , and calcium is associated with reduced stroke risk among men . Methods We prospect ively examined the associations between intakes of magnesium , potassium , and calcium from diet and supplements , and the risk of incident stroke among 42 669 men in the Health Professionals Follow-up Study , aged 40 to 75 years and free of diagnosed cardiovascular disease and cancer at baseline in 1986 . We calculated the hazard ratio of total , ischemic , and haemorrhagic strokes by quintiles of each cation intake , and of a combined dietary score of all three cations , using multivariate Cox proportional hazard models . Results During 24 years of follow-up , 1547 total stroke events were documented . In multivariate analyses , the relative risks and 95 % confidence intervals of total stroke for men in the highest vs. lowest quintile were 0·87 ( 95 % confidence interval , 0·74–1·02 ; P , trend = 0·04 ) for dietary magnesium , 0·89 ( 95 % confidence interval , 0·76–1·05 ; P , trend = 0·10 ) for dietary potassium , and 0·89 ( 95 % confidence interval , 0·75–1·04 ; P , trend = 0·25 ) for dietary calcium intake . The relative risk of total stroke for men in the highest vs. lowest quintile was 0·74 ( 95 % confidence interval , 0·59–0·93 ; P , trend = 0·003 ) for supplemental magnesium , 0·66 ( 95 % confidence interval , 0·50–0·86 ; P , trend = 0·002 ) for supplemental potassium , and 1·01 ( 95 % confidence interval , 0·84–1·20 ; P , trend = 0·83 ) for supplemental calcium intake . For total intake ( dietary and supplemental ) , the relative risk of total stroke for men in the highest vs. lowest quintile was 0·83 ( 95 % confidence interval , 0·70–0·99 ; P , trend = 0·04 ) for magnesium , 0·88 ( 95 % confidence interval , 0·75–4 ; P , trend = 6 ) for potassium , and 3 ( 95 % confidence interval , 79–09 ; P , trend = 84 ) for calcium . Men in the highest quintile for a combined dietary score of all three cations had a multivariate relative risk of 0·79 ( 95 % confidence interval , 0·67–0·92 ; P , trend = 0·008 ) for total stroke , compared with those in the lowest . Conclusions A diet rich in magnesium , potassium , and calcium may contribute to reduced risk of stroke among men . Because of significant collinearity , the independent contribution of each cation is difficult to define OBJECTIVE R and omized treatment comparing an intensive glycemic treatment strategy with a st and ard strategy in the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial was ended early because of an unexpected excess of mortality in the intensive arm . As part of ongoing post hoc analyses of potential mechanisms for this finding , we explored whether on-treatment A1C itself had an independent relationship with mortality . RESEARCH DESIGN AND METHODS Participants with type 2 diabetes ( n = 10,251 with mean age 62 years , median duration of diabetes 10 years , and median A1C 8.1 % ) were r and omly assigned to treatment strategies targeting either A1C < 6.0 % ( intensive ) or A1C 7.0–7.9 % ( st and ard ) . Data obtained during 3.4 ( median ) years of follow-up before cessation of intensive treatment were analyzed using several multivariable models . RESULTS Various characteristics of the participants and the study sites at baseline had significant associations with the risk of mortality . Before and after adjustment for these covariates , a higher average on-treatment A1C was a stronger predictor of mortality than the A1C for the last interval of follow-up or the decrease of A1C in the first year . Higher average A1C was associated with greater risk of death . The risk of death with the intensive strategy increased approximately linearly from 6–9 % A1C and appeared to be greater with the intensive than with the st and ard strategy only when average A1C was > 7 % . CONCLUSIONS These analyses implicate factors associated with persisting higher A1C levels , rather than low A1C per se , as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD AIM This study evaluated the efficacy of oral magnesium supplementation in the reduction of plasma glucose levels in adults with prediabetes and hypomagnesaemia . METHODS A total of 116 men and non-pregnant women , aged 30 to 65 years with hypomagnesaemia and newly diagnosed with prediabetes , were enrolled into a r and omized double-blind placebo-controlled trial to receive either 30 mL of MgCl2 5 % solution ( equivalent to 382 mg of magnesium ) or an inert placebo solution once daily for four months . The primary trial endpoint was the efficacy of magnesium supplementation in reducing plasma glucose levels . RESULTS At baseline , there were no significant statistical differences in terms of anthropometric and biochemical variables between individuals in the supplement and placebo groups . At the end of follow-up , fasting ( 86.9 ± 7.9 and 98.3 ± 4.6 mg/dL , respectively ; P = 0.004 ) and post-load glucose ( 124.7 ± 33.4 and 136.7 ± 23.9 mg/dL , respectively ; P = 0.03 ) levels , HOMA-IR indices ( 2.85 ± 1.0 and 4.1 ± 2.7 , respectively ; P = 0.04 ) and triglycerides ( 166.4 ± 90.6 and 227.0 ± 89.7 , respectively ; P = 0.009 ) were significantly decreased , whereas HDL cholesterol ( 45.6 ± 10.9 and 46.8 ± 9.2 mg/dL , respectively ; P = 0.04 ) and serum magnesium ( 1.96 ± 0.27 and 1.60 ± 0.26 mg/dL , respectively ; P = 0.005 ) levels were significantly increased in those taking MgCl2 compared with the controls . A total of 34 ( 29.4 % ) people improved their glucose status ( 50.8 % and 7.0 % in the magnesium and placebo groups , respectively ; P < 0.0005 ) . CONCLUSION Our results show that magnesium supplementation reduces plasma glucose levels , and improves the glycaemic status of adults with prediabetes and hypomagnesaemia Background Japanese diets contain a relatively high amount of carbohydrates , and its high dietary glycemic index and glycemic load may raise the risk of diabetes in the Japanese population . The current study evaluated the associations between the dietary glycemic index , glycemic load , and the risk of type 2 diabetes in a population based cohort in Japan . Methods We observed 27,769 men and 36,864 women ( 45–75 y ) who participated in the second survey of the Japan Public Health Center-based Prospect i ve Study . The dietary glycemic index and glycemic load were estimated using a food-frequency question naire . The development of diabetes was reported in a question naire administered five years later , and the associations were analyzed using logistic regression after controlling for age , area , total energy intake , smoking status , family history of diabetes , physical activity , hypertension , BMI , alcohol intake , magnesium , calcium , dietary fiber and coffee intake , and occupation . Results The dietary glycemic load was positively associated with the risk of diabetes among women : the multivariable-adjusted odds ratio comparing the highest vs. the lowest quartile was 1.52 ( 95 % CI , 1.13 - 2.04 ; P-trend = 0.01 ) . The association was implied to be stronger among women with BMI < 25 than the women with BMI ≥ 25 . The dietary glycemic index was positively associated with the risk of diabetes among men with a high intake of total fat : the multivariable-adjusted odds ratio comparing the highest vs. the lowest quartile was 1.46 ( 95 % CI , 0.94 - 2.28 ; P-trend = 0.04 ) . Among women with a high total fat intake , those in the first and second quartiles of the dietary glycemic index had a significant reduced risk of diabetes , compared with those in the first quartile who had a lower total fat level ( multivariable-adjusted odds ratio = 0.59 with 95 % CI , 0.37 - 0.94 , and odds ratio = 0.63 with 95 % CI , 0.40 - 0.998 respectively ) . Conclusions The population -based cohort study in Japan indicated that diets with a high dietary glycemic load increase the risk of type 2 diabetes among women . Total fat intake may modify the association between the dietary glycemic index and the risk of type 2 diabetes among men and women OBJECTIVE The purpose of this study was to prospect ively examine the association between vitamin D and calcium intake and risk of type 2 diabetes . RESEARCH DESIGN AND METHODS In the Nurses ' Health Study , we followed 83,779 women who had no history of diabetes , cardiovascular disease , or cancer at baseline for the development of type 2 diabetes . Vitamin D and calcium intake from diet and supplements was assessed every 2 - 4 years . During 20 years of follow-up , we documented 4,843 incident cases of type 2 diabetes . RESULTS After adjusting for multiple potential confounders , there was no association between total vitamin D intake and type 2 diabetes . However , the relative risk ( RR ) of type 2 diabetes was 0.87 ( 95 % CI 0.75 - 1.00 ; P for trend = 0.04 ) comparing the highest with the lowest category of vitamin D intake from supplements . The multivariate RRs of type 2 diabetes were 0.79 ( 0.70 - 0.90 ; P for trend < 0.001 ) comparing the highest with the lowest category of calcium intake from all sources and 0.82 ( 0.72 - 0.92 ; P for trend < 0.001 ) comparing the highest with the lowest category of calcium intake from supplements . A combined daily intake of > 1,200 mg calcium and > 800 IU vitamin D was associated with a 33 % lower risk of type 2 diabetes with RR of 0.67 ( 0.49 - 0.90 ) compared with an intake of < 600 mg and 400 IU calcium and vitamin D , respectively . CONCLUSIONS The results of this large prospect i ve study suggest a potential beneficial role for both vitamin D and calcium intake in reducing the risk of type 2 diabetes Background The worldwide epidemic of type 2 diabetes requires effective prevention . We determined the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention , originally demonstrated during the 3-year Diabetes Prevention Program ( DPP ) , and whether diabetes-associated microvascular complications are reduced . Methods The DPP ( 1996–2001 ) was a r and omized trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk to develop diabetes . All participants were offered lifestyle training at DPP-end . 2776 ( 88 % ) of the surviving DPP cohort were followed in the DPP Outcome Study ( DPPOS 2002–2013 ) and analyzed by intention-to-treat based on original DPP assignment . During DPPOS , the lifestyle group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin . Findings During 15 years of average follow-up , lifestyle intervention and metformin reduced diabetes incidence rates by 27 % ( p<0.0001 ) and 18 % ( p=0.001 ) , respectively , compared with the placebo group , with declining between group differences over time . At year 15 , the cumulative incidences of diabetes were 55 , 56 and 62 % , respectively . The prevalences at study -end of the aggregate microvascular outcome , composed of nephropathy , neuropathy , and retinopathy , were not significantly different among the treatment groups ( 11–13 % ) in the total cohort . However , in women ( n=1887 ) lifestyle intervention was associated with a lower prevalence ( 8.7 % ) than in the placebo ( 11 % ) and metformin ( 11.2 % ) groups , with 21 % ( p=0.03 ) and 22 % ( p=0.02 ) reductions with lifestyle compared with placebo and metformin , respectively . Compared with participants who progressed to diabetes , those who did n’t progress had a 28 % lower prevalence of microvascular complications ( p<0.0001 ) . Interpretation Lifestyle intervention or metformin significantly reduce diabetes development over 15 years . There were no overall differences in the aggregate microvascular outcome among treatment groups ; however , those who did not progress to diabetes had a lower prevalence of microvascular complications than those who progressed . Funding National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK BACKGROUND A high intake of magnesium , calcium , and potassium and a low intake of sodium have been hypothesized to reduce the risk of stroke . However , prospect i ve data relating intake of these minerals to risk of stroke are inconsistent . METHODS We examined the relationship of dietary magnesium , calcium , potassium , and sodium intake with risk of stroke in a cohort of 26 556 Finnish male smokers , aged 50 to 69 years , who were free from stroke at baseline . Dietary intake was assessed at baseline using a detailed and vali date d food frequency question naire . During a mean follow-up of 13.6 years ( 1985 - 2004 ) , 2702 cerebral infa rct ions , 383 intracerebral hemorrhages , and 196 subarachnoid hemorrhages were identified in the national registries . RESULTS After adjustment for age and cardiovascular risk factors , a high magnesium intake was associated with a statistically significant lower risk of cerebral infa rct ion but not with intracerebral or subarachnoid hemorrhages . The multivariate relative risk of cerebral infa rct ion was 0.85 ( 95 % confidence interval , 0.76 - 0.97 ; P for trend = .004 ) for men in the highest quintile of magnesium intake compared with those in the lowest quintile . The inverse association between magnesium intake and cerebral infa rct ion was stronger in men younger than 60 years ( relative risk , 0.76 ; 95 % confidence interval , 0.64 - 0.89 ; P for interaction = .02 ) . Calcium , potassium , and sodium intake was not significantly associated with risk of any subtype of stroke ( P for trend > .05 ) . CONCLUSION These findings in male smokers suggest that a high magnesium intake may play a role in the primary prevention of cerebral infa rct ion Background and Purpose — We aim ed to investigate the associations of dietary and total potassium , magnesium , and calcium intakes with stroke occurrence . Methods — A prospect i ve cohort study was conducted among 36 094 participants aged 21 to 70 years . Dietary intake was assessed with a food frequency question naire . Results — During 12 years of follow-up , 631 strokes occurred . After adjustment for confounders , magnesium intake was associated with reduced stroke risk ( hazard ratio [ 95 % confidence interval ] per 100 mg/d , 0.80 [ 0.67–0.97 ] dietary magnesium ; 0.78 [ 0.65–0.93 ] total magnesium ) . Potassium and calcium intakes were not associated with stroke . Conclusions — This study supports an association between high magnesium intake and a reduced stroke risk BACKGROUND Coffee intake may be associated with reduced risk of type 2 diabetes mellitus because of minerals , phytochemicals , and antioxidants in coffee , but the role of caffeine is unclear . Our objective was to examine the association between total , caffeinated , and decaffeinated coffee intake , as assessed by food frequency question naire at baseline , and risk of incident type 2 diabetes mellitus . METHODS This prospect i ve analysis of the Iowa Women 's Health Study ( 1986 - 1997 ) included 28 812 postmenopausal women free of diabetes and cardiovascular disease in the general community . The main outcome measure was incident type 2 diabetes mellitus as determined by mailed question naire . RESULTS Coffee intake was categorized as 0 , less than 1 , 1 to 3 , 4 to 5 , and 6 or more cups per day . During 11 years of follow-up , there were 1418 incident cases of diabetes . Relative risks ( RRs ) were adjusted for a variety of demographic , adiposity , and lifestyle measures . Compared with women who reported 0 cups of coffee per day , women who consumed 6 or more cups per day had a 22 % lower risk ( RR = 0.78 ; 95 % confidence interval [ CI ] , 0.61 - 1.01 ) of diabetes ( P for linear trend across categories , .06 ) . This association appeared to be largely explained by decaffeinated coffee ( RR = 0.67 ; 95 % CI , 0.42 - 1.08 ; P for trend , .006 ) rather than regular coffee ( RR = 0.79 ; 95 % CI , 0.59 - 1.05 ; P for trend , .90 ) . Intake of magnesium and phytate did not explain these associations . Intakes of caffeine from all sources was not associated with risk of diabetes . CONCLUSION Coffee intake , especially decaffeinated , was inversely associated with risk of type 2 diabetes mellitus in this cohort of postmenopausal women OBJECTIVE Higher intake of magnesium appears to improve glucose and insulin homeostasis ; however , there are sparse prospect i ve data on the association between magnesium intake and incidence of type 2 diabetes . RESEARCH DESIGN AND METHODS In the Women 's Health Study , a cohort of 39,345 U.S. women aged > /=45 years with no previous history of cardiovascular disease , cancer , or type 2 diabetes completed vali date d semiquantitative food frequency question naires in 1993 and were followed for an average of 6 years . We used Cox proportional hazard models to estimate multivariate relative risks ( RRs ) of type 2 diabetes across quintiles of magnesium intake compared with the lowest quintile . In a sample of 349 apparently healthy women from this study , we measured plasma fasting insulin levels to examine their relation to magnesium intake . RESULTS During 222,523 person-years of follow-up , we documented 918 confirmed incident cases of type 2 diabetes . There was a significant inverse association between magnesium intake and risk of type 2 diabetes , independent of age and BMI ( P = 0.007 for trend ) . After further adjustment for physical activity , alcohol intake , smoking , family history of diabetes , and total calorie intake , the multivariate-adjusted RRs of diabetes from the lowest to highest quintiles of magnesium intake were attenuated at 1.0 , 1.06 , 0.81 , 0.86 , and 0.89 ( P = 0.05 for trend ) . Among women with BMI > /=25 kg/m2 , the inverse trend was significant ; multivariate-adjusted RRs were 1.0 , 0.96 , 0.76 , 0.84 , and 0.78 ( P = 0.02 for trend ) . Multivariate-adjusted geometric mean insulin levels for overweight women in the lowest quartile of magnesium intake was 53.5 compared with 41.5 pmol/l among those at the highest quartile ( P = 0.03 for trend ) . CONCLUSIONS These findings support a protective role of higher intake of magnesium in reducing the risk of developing type 2 diabetes , especially in overweight women BACKGROUND Diet plays a key role in the development of type 2 diabetes ( T2D ) , but little is known about the contributions of specific nutrients in population s in which dietary patterns differ from Western population s. OBJECTIVE We examined associations between calcium and magnesium intakes and the risk of T2D in a Chinese population . DESIGN We used data from a population -based , prospect i ve study of 64,191 women who were free of T2D or other chronic diseases at study recruitment and were living in urban Shanghai , China . Dietary intake , physical activity , and anthropometric measurements were assessed through in-person interviews . A Cox regression model was used to evaluate the association of the exposures under study with the risk of T2D . RESULTS An inverse association between calcium and magnesium intakes and T2D risk was observed . The relative risks for the lowest to the highest quintiles of calcium intake were 1.00 , 0.82 , 0.73 , 0.67 , and 0.74 ( P for trend < 0.001 ) , and for magnesium they were 1.00 , 0.84 , 0.84 , 0.79 , and 0.86 ( P for trend < 0.001 ) . Milk intake was also inversely associated with the risk of T2D . CONCLUSION Our data suggest that calcium and magnesium intakes may protect against the development of T2D in this population OBJECTIVES This study examined the association between intake of whole vs refined grain and the risk of type 2 diabetes mellitus . METHODS We used a food frequency question naire for repeated dietary assessment s to prospect ively evaluate the relation between whole-grain intake and the risk of diabetes mellitus in a cohort of 75,521 women aged 38 to 63 years without a previous diagnosis of diabetes or cardiovascular disease in 1984 . RESULTS During the 10-year follow-up , we confirmed 1879 incident cases of diabetes mellitus . When the highest and the lowest quintiles of intake were compared , the age and energy-adjusted relative risks were 0.62 ( 95 % confidence interval [ CI ] = 0.53 , 0.71 , P trend < .0001 ) for whole grain , 1.31 ( 95 % CI = 1.12 , 1.53 , P trend = .0003 ) for refined grain , and 1.57 ( 95 % CI = 1.36 , 1.82 , P trend < .0001 ) for the ratio of refined- to whole-grain intake . These findings remained significant in multivariate analyses . The findings were most evident for women with a body mass index greater than 25 and were not entirely explained by dietary fiber , magnesium , and vitamin E. CONCLUSIONS These findings suggest that substituting whole- for refined-grain products may decrease the risk of diabetes mellitus OBJECTIVE To examine prospect ively the relationship between glycemic diets , low fiber intake , and risk of non-insulin-dependent diabetes mellitus . DESIGN Cohort study . SETTING In 1986 , a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease , cancer , and diabetes completed a detailed dietary question naire from which we calculated usual intake of total and specific sources of dietary fiber , dietary glycemic index , and glycemic load . MAIN OUTCOME MEASURE Non-insulin-dependent diabetes mellitus . RESULTS During 6 years of follow-up , 915 incident cases of diabetes were documented . The dietary glycemic index was positively associated with risk of diabetes after adjustment for age , body mass index , smoking , physical activity , family history of diabetes , alcohol and cereal fiber intake , and total energy intake . Comparing the highest with the lowest quintile , the relative risk ( RR ) of diabetes was 1.37 ( 95 % confidence interval [ CI ] , 1.09 - 1.71 , P trend=.005 ) . The glycemic load ( an indicator of a global dietary insulin dem and ) was also positively associated with diabetes ( RR= 1.47 ; 95 % CI , 1.16 - 1.86 , P trend=.003 ) . Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles ( RR=0.72 , 95 % CI , 0.58 - 0.90 , P trend=.001 ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes ( RR=2.50 , 95 % CI , 1.14 - 5.51 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes BACKGROUND / PURPOSE Several studies have indicated an inverse association between the incidence of diabetes mellitus and magnesium and dietary fiber intake . Few studies have examined both of these associations together , not to mention in Asian population s with prospect i ve study design . We therefore aim ed to study how dietary magnesium and fiber intake levels affect diabetes incidence separately or in combination , in a prospect i ve study in Taiwan . METHODS The study subjects were recruited for a longitudinal study , CardioVascular Disease risk FACtor Two-township Study cycle 2 from November 1990 . Data from complete baseline information on dietary and biochemical profile and at least one additional follow-up visit were gathered on a total of 1604 healthy subjects aged 30 years and over . Cox proportional hazard model was used to study the association between diabetes incidence and dietary magnesium and fiber intake level estimated from a food frequency question naire . RESULTS A total of 141 diabetes mellitus events were identified and confirmed during the 4.6 years of follow-up ( 7365.1 person-years ) . A significantly higher diabetes risk was observed for people in the lowest quintile of total dietary fiber intake ( hazard ratio = 2.04 ; 95 % CI = 1.17 - 3.53 ) and magnesium intake ( hazard ratio = 2.61 ; 95 % CI = 1.42 - 4.79 ) compared with the highest quintile after adjusting for traditional cardiovascular disease risk factors . Similar inverse associations for total dietary fiber were also shown for vegetable fiber and fruit fiber . CONCLUSION Lower magnesium , lower total dietary fiber intake , or lower intake of both was associated with higher risk of diabetes in the Taiwanese population . Clinical trials are required to confirm the protective effects of the adequate intake of fiber , magnesium , and /or their combination Aims /hypothesisCalcium and vitamin D have been implicated in the development of type 2 diabetes , but epidemiological evidence is limited . We examined prospect ively the relation of calcium and vitamin D intake to type 2 diabetes risk in a Japanese cohort . Methods Participants were 59,796 middle-aged and older men and women , who participated in the Japan Public Health Center-based Prospect i ve Study and had no history of type 2 diabetes or other serious diseases . Dietary intake of calcium and vitamin D were estimated using a vali date d food frequency question naire . Logistic regression was used to assess the association between intake of these nutrients and self-reported newly diagnosed type 2 diabetes . Results During a 5 year follow-up , 1,114 cases of type 2 diabetes were documented . Overall , calcium intake was not associated with a significantly lower risk of type 2 diabetes ; the multivariable odds ratio for the highest vs lowest quartiles was 0.93 ( 95 % CI 0.71–1.22 ) in men and 0.76 ( 95 % CI 0.56–1.03 ) in women . However , among participants with a higher vitamin D intake , calcium intake was inversely associated with diabetes risk ; the odds ratio for the highest vs lowest intake categories was 0.62 ( 95 % CI 0.41–0.94 ) in men and 0.59 ( 95 % CI 0.38–0.91 ) in women . Dairy food intake was significantly associated with a lower risk of type 2 diabetes in women only . Conclusions /interpretationCalcium and vitamin D may not be independently associated with type 2 diabetes risk . Our finding suggesting a joint action of these nutrients against type 2 diabetes warrants further investigation OBJECTIVE Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM , whereas dietary fiber is suspected to reduce incidence . These hypotheses have not been evaluated prospect ively . RESEARCH DESIGN AND METHODS We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease , who were 40–75 years of age in 1986 . Diet was assessed at baseline by a vali date d semiquantitative food frequency question naire . During 6-years of follow-up , 523 incident cases of NIDDM were documented . RESULTS The dietary glycemic index ( an indicator of carbohydrate 's ability to raise blood glucose levels ) was positively associated with risk of NIDDM after adjustment for age , BMI , smoking , physical activity , family history of diabetes , alcohol consumption , cereal fiber , and total energy intake . Comparing the highest and lowest quintiles , the relative risk ( RR ) of NIDDM was 1.37 ( 95 % CI , 1.02–1.83 , P trend = 0.03 ) . Cereal fiber was inversely associated with risk of NIDDM ( RR = 0.70 ; 95 % CI , 0.51–0.96 , P trend = 0.007 ; for > 8.1 g/day vs. < 3.2 g/day ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM ( RR = 2.17 , 95 % CI , 1.04–4.54 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM BACKGROUND Experimental studies in animals and cross-sectional studies in humans have suggested that low serum magnesium levels might lead to type 2 diabetes ; however , this association has not been examined prospect ively . METHODS We assessed the risk for type 2 diabetes associated with low serum magnesium level and low dietary magnesium intake in a cohort of nondiabetic middle-aged adults ( N = 12,128 ) from the Atherosclerosis Risk in Communities Study during 6 years of follow-up . Fasting serum magnesium level , categorized into 6 levels , and dietary magnesium intake , categorized into quartiles , were measured at the baseline examination . Incident type 2 diabetes was defined by self-report of physician diagnosis , use of diabetic medication , fasting glucose level of at least 7.0 mmol/L ( 126 mg/dL ) , or nonfasting glucose level of at least 11.1 mmol/L ( 200 mg/dL ) . RESULTS Among white participants , a grade d inverse relationship between serum magnesium levels and incident type 2 diabetes was observed . From the highest to the lowest serum magnesium levels , there was an approximate 2-fold increase in incidence rate ( 11.1 , 12.2 , 13.6 , 12.8 , 15.8 , and 22.8 per 1000 person-years ; P = .001 ) . This grade d association remained significant after simultaneous adjustment for potential confounders , including diuretic use . Compared with individuals with serum magnesium levels of 0.95 mmol/L ( 1.90 mEq/L ) or greater , the adjusted relative odds of incident type 2 diabetes rose progressively across the following lower magnesium categories : 1.13 ( 95 % CI , 0.79 - 1.61 ) , 1.20 ( 95 % CI , 0.86 - 1.68 ) , 1.11 ( 95 % CI , 0.80 - 1.56 ) , 1.24 ( 95 % CI , 0.86 - 1.78 ) , and 1.76 ( 95 % CI , 1.18 - 2.61 ) ( for trend , P = .01 ) . In contrast , little or no association was observed in black participants . No association was detected between dietary magnesium intake and the risk for incident type 2 diabetes in black or white participants . CONCLUSIONS Among white participants , low serum magnesium level is a strong , independent predictor of incident type 2 diabetes . That low dietary magnesium intake does not confer risk for type 2 diabetes implies that compartmentalization and renal h and ling of magnesium may be important in the relationship between low serum magnesium levels and the risk for type 2 diabetes AIMS Early studies have shown that magnesium intake decreases the risk of Type 2 diabetes , but the results are still inconsistent . We prospect ively examined the association between magnesium intake and incidence of Type 2 diabetes in a general Japanese population . METHODS A total of 1999 subjects without diabetes aged 40 - 79 years who underwent a 75-g oral glucose tolerance test were followed up prospect ively for a mean of 15.6 years . RESULTS During the follow-up , 417 subjects developed Type 2 diabetes . The age- and sex-adjusted incidence of Type 2 diabetes significantly decreased with increasing magnesium intake quartile levels ( ≤ 148.5 , 148.6 - 171.5 , 171.6 - 195.5 and ≥ 195.6 mg/day , P for trend = 0.01 ) . In multivariate analyses , after adjusting for comprehensive risk factors and other dietary factors , the hazard ratio of Type 2 diabetes was 0.67 ( 95 % CI 0.49 - 0.92 ; P = 0.01 ) in the third quartile and 0.63 ( 95 % CI 0.44 - 0.90 ; P = 0.01 ) in the highest quartile compared with the first quartile . In addition , the risk of Type 2 diabetes was 14 % lower ( P = 0.04 ) for a 1-sd increment of log-transformed magnesium intake in the multivariate-adjusted model . In stratified analysis , there were statistically significant interactions between magnesium intake and levels of homeostasis model assessment of insulin resistance , high-sensitivity C-reactive protein or alcohol intake on the risk of Type 2 diabetes ( all P < 0.05 ) . CONCLUSIONS Our findings suggest that increased magnesium intake was a significant protective factor for the incidence of Type 2 diabetes in the general Japanese population , especially among subjects with insulin resistance , low- grade inflammation and a drinking habit Dietary supplementation is approximately a $ 30 billion industry in the United States , with more than 90 000 products on the market . In recent national surveys , 52 % of US adults reported use of at least 1 supplement product , and 10%reporteduseofatleast4suchproducts.1 Vitamins and minerals are among the most popular supplements and are taken by 48 % and 39 % of adults , respectively , typically to maintain health and prevent disease . Despite this enthusiasm , most r and omized clinical trials of vitamin and mineral supplements have not demonstrated clear benefits for primary or secondary prevention of chronic diseases not related to nutritional deficiency . Indeed , some trials suggest that micronutrient supplementation in amounts that exceed the recommended dietary allowance (RDA)—eg , high doses of beta carotene , folic acid , vitamin E , or selenium — may have harmful effects , including increased mortality , cancer , and hemorrhagic stroke.2 In this Viewpoint , we provide information to help clinicians address frequently asked questions about micronutrient supplements from patients , as well as promote appropriate use and curb inappropriate use of such supplements among generally healthy individuals . Importantly , clinicians should counsel their patients that such supplementation is not a substitute for a healthful and balanced diet and , in most cases , provides little if any benefit beyond that conferred by such a diet . Clinicians should also highlight the many advantages of obtaining vitamins and minerals from food instead of from supplements . Micronutrients in food are typically better absorbed by the body and are associated with fewer potential adverse effects.2,3 A healthful diet provides an array of nutritionally important substances in biologically optimal ratios as opposed to isolated compounds in highly concentrated form . Indeed , research shows that positive health outcomes are more strongly related to dietary patterns and specific food types than to individual micronutrient or nutrient intakes.3 Although routine micronutrient supplementation is not recommended for the general population , targeted supplementation may be warranted in high-risk groups for whom nutritional requirements may not be met through diet alone , including people at certain life stages and those with specific risk factors ( discussed in the next 3 sections and in the Box ) BACKGROUND Dietary magnesium could modify the major stroke risk factors , high blood pressure ( BP ) and cholesterol , but has been understudied in both sexes in a single population . This study aim ed to investigate if dietary magnesium intake was associated with BP , total cholesterol ( TC ) and incident stroke risk in an adult population . METHODS We conducted cross-sectional analyses in a case-cohort study of 4443 , men and women aged 40 - 75 , representative of 25,639 participants years of the EPIC ( European Prospect i ve Investigation into Cancer)-Norfolk cohort . The cohort included 928 stroke cases ( 42,556.5 person years ) . Dietary data from 7 day food diaries were analysed using multivariate regression to assess associations between quintiles or data -derived categories of dietary magnesium intake and BP , TC and stroke risk , adjusted for relevant confounders . RESULTS We observed differences of -7 mmHg systolic BP ( P trend ≤ 0.01 ) and -3.8 mmHg diastolic BP ( P trend=0.01 ) between extreme intakes of magnesium in men , a significant inverse association with TC was observed ( P trend=0.02 men and 0.04 women ) . Compared to the bottom 10 % , the top 30 % of magnesium intake was associated with a 41 % relative reduction in stroke risk ( HR 0.59 ; 95 % CI 0.38 - 0.93 ) in men . CONCLUSIONS Lower dietary magnesium intake was associated with higher BP and stroke risk , which may have implication s for primary prevention |
10,382 | 22,037,559 | All-cause mortality was low in our analysis of patients attending specialty clinics .
In terms of spinal steroid injections , headache appeared to be the most common adverse effect .
Oral opioid therapy may be helpful for the treatment of low back pain , but it is unclear from the high- quality literature whether there are limitations from adverse effects .
Spinal steroid injections are beneficial for low back pain and disability in the short-term .
The high dropout rates caused by insufficient pain relief and adverse effects suggest that opioids may not be as effective as spinal steroid injections .
There is more high- quality literature to support the use of spinal steroid injections compared with oral opioids in this condition | OBJECTIVE The aim of this study was to examine the outcomes related to analgesia , function , mortality , and adverse effects of oral opioid analgesics and spinal steroid injections on low back pain syndromes . | Objective : To determine the efficacy of epidural corticosteroid injections for sciatica . Methods : Three epidural injections ( two day intervals ) of 2 ml prednisolone acetate ( 50 mg ) or 2 ml isotonic saline were administered to patients with sciatica presumably due to a disk herniation lasting 15–180 days . Self evaluation was the main judgment criterion at day 20 . Patients who recovered or showed marked improvement were considered as success . Pain measured by VAS , the SLR test , Schober ’s test , Dallas pain question naire , and the Rol and -Morris index were evaluated at days 0 , 5 , 20 , and 35 . Only analgesics were authorised , patients requiring non-steroidal anti-inflammatory drugs ( NSAIDs ) before day 20 were considered as failure . Results : 42 patients were included in the control group ( CG ) , 43 in the steroid group ( SG ) . On an intention to treat analysis 15/42 ( 36 % ) in the CG and 22/43 ( 51 % ) in the SG ( p=0.15 ) were considered as success ( difference 15.5 % , 95 % CI ( −5.4 to 36.3 ) ) . Among the 48 failures , 14 patients ( 6 CG , 8 SG ) required NSAIDs , 3 ( 2 CG , 1 SG ) required surgery , and 7 ( 3 CG , 4 SG ) other treatments . On analysis according to protocol , in 74 remaining patients 12/35 ( 34 % ) in the CG and 22/39 ( 56 % ) in the SG ( p=0.057 ) were considered as success ( difference 22.1 % , 95 % CI ( 0.0 to 44.2 ) ) . For all secondary end points intragroup improvement with time was significant , but intergroup differences were not . Conclusion : The efficacy of isotonic saline administered epidurally for sciatica can not be excluded , but epidural steroid injections provide no additional improvement The management of sciatica due to lumbar nerve root compromise remains controversial , probably because few well-controlled studies of conservative management have been performed . This preliminary study assesses the efficacy of epidural injections of 80 mg triamcinolone acetonide plus 0.5 % procaine hydrochloride in saline , administered via the caudal route , in a double-blind , placebo controlled trial with 1 year follow-up . Twenty-three patients were entered into the study : 12 received treatment and 11 placebo . The active group showed significant pain relief ( P=0.02 ) and a significant increase in mobility ( P=0.01 ) at 4 weeks , which result ed in improved quality of life ( P=0.02 ) . At 1 year , subjective and objective measures improved in both groups . The improvement was greater in the actively treated group , but only the objective assessment ( straight leg raise ) was statistically significant BACKGROUND Although epidural corticosteroid injections are commonly used for sciatica , their efficacy has not been established . METHODS In a r and omized , double-blind trial , we administered up to three epidural injections of methylprednisolone acetate ( 80 mg in 8 ml of isotonic saline ) or isotonic saline ( 1 ml ) to 158 patients with sciatica due to a herniated nucleus pulposus . All patients had Oswestry disability scores higher than 20 ( on a scale of 1 to 100 , with scores of 20 or less indicating minimal disability , and higher scores greater disability ) . RESULTS At three weeks , the Oswestry score had improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the placebo group ( 95 percent confidence interval for the difference , -7.1 to 2.2 ) . Differences in improvements between the groups were not significant , except for improvements in the finger-to-floor distance ( P=0.006 ) and sensory deficits ( P=0.03 ) , which were greater in the methylprednisolone group . After six weeks , the only significant difference was the improvement in leg pain , which was greater in the methylprednisolone group ( P=0.03 ) . After three months , there were no significant differences between the groups . The Oswestry score had improved by a mean of -17.3 in the methylprednisolone group and -15.4 in the placebo group ( 95 percent confidence interval for the difference , -9.3 to 5.4 ) . At 12 months , the cumulative probability of back surgery was 25.8 percent in the methylprednisolone group and 24.8 percent in the placebo group ( P=0.90 ) . CONCLUSIONS Although epidural injections of methylprednisolone may afford short-term improvement in leg pain and sensory deficits in patients with sciatica due to a herniated nucleus pulposus , this treatment offers no significant functional benefit , nor does it reduce the need for surgery The value of epidural injections of corticosteroid as an outpatient treatment of sciatica has been hitherto uncertain . An epidural injection of 80 mg methylprednisolone in 10 ml physiological saline was compared with an interspinous injection of 2 ml physiological saline in a double blind fashion amongst 39 out patients . Significant differences of pain relief were seen between the two groups within 2 weeks . This benefit disappeared for six ( 35 % ) patients within 6 months of treatment although 11 ( 65 % ) successfully treated subjects had sustained improvement up to this time . Outpatient epidural injections of corticosteroid are thus a useful short-term means of relieving pain in sciatica but probably have little effect on the long-term natural history of symptoms . Factors associated with a failure to respond to epidural steroid injections are discussed OBJECTIVE To determine the effectiveness and predictors of response to lumbar epidural corticosteroid injections ( ESI ) in patients with sciatica . We performed a 12-month , multicentre , double-blind , r and omized , placebo-controlled , parallel-group trial in four secondary pain-care clinics in the Wessex Region . METHODS Two hundred and twenty-eight patients with a clinical diagnosis of unilateral sciatica of 1 - 18 months ' duration were r and omized to either three lumbar ESIs of triamcinolone acetonide or interligamentous saline injections at intervals of 3 weeks . The main outcome measure was the Oswestry low back pain disability question naire ( ODQ ) . RESULTS At 3 weeks , the ESI group demonstrated a transient benefit over the placebo group ( patients achieving a 75 % improvement in ODQ , 12.5 vs 3.7 % ; number needed to treat , 11.4 ) . No benefit was demonstrated from 6 to 52 weeks . ESIs did not improve physical function , hasten return to work or reduce the need for surgery . There was no benefit of repeated ESIs over single injection . No clinical predictors of response were found . At the end of the study the majority of patients still had significant pain and disability regardless of intervention . CONCLUSIONS In this pragmatic study , ESIs offered transient benefit in symptoms at 3 weeks in patients with sciatica , but no sustained benefits in terms of pain , function or need for surgery . Sciatica is a chronic condition requiring a multidisciplinary approach . To fully investigate the value of ESIs , they need to be evaluated as part of a multidisciplinary approach OBJECTIVE To determine the difference in short- and long-term pain improvement between lumbar Epidural Steroid Injections ( ESIs ) and conservative management in patients with lumbar radiculopathy . STUDY DESIGN Quasi-experimental study . PLACE AND DURATION OF STUDY The Postgraduate Medical Institute of Hayatabad Medical Complex , Peshawar , from April 2005 to March 2007 . METHODOLOGY Fifty elective patients fulfilling the inclusion criteria were r and omly divided into two groups . Patients in the steroid group were treated with 80 mg of methylprednisolone injected in combination with 3 ml of 2 % plain xylocaine and 3 ml of normal saline in the lumbar epidural space , while patients in the conservative group were treated with bed rest , non-steroidal anti-inflammatory agents , muscle relaxants , and opioids . All the 50 patients in the two groups were regularly assessed at 2 weeks , 1 month , 3 months and 6 months of periods for pain score by the Visual Analogue Scale ( VAS ) , patients satisfaction score and any unwanted side effects . RESULTS A marked improvement of the pain score and patients satisfaction score were noticed in the steroid group . Less significant improvement was seen in the conservative group during the initial period i.e 2 weeks and 1 month ( p < 0.05 ) . The difference in Visual Analogue Scale ( VAS ) and patients satisfaction score was non-significant in chronic stages of treatment in both groups ( p > 0.05 ) . CONCLUSION Epidural steroid injections in acute symptoms of sciatica are considered to be a better option compared to conservative treatment OBJECTIVE Low back pain is a highly common problem and causes much morbidity and socioeconomic loss in the community . Although the use of caudal epidural injections in the management of the low back pain with radicular signs is commonplace , it has not been well investigated . We compare the effectiveness of caudal epidural injection versus non-steroidal anti-inflammatory drugs ( NSAIDs ) in the treatment of low back pain accompanied with radicular pain . METHODS The study was a controlled prospect i ve unblinded trial . A total of consecutive 64 patients with subacute or chronic low back pain accompanied with radicular pain were included . The patients were r and omly allocated to two groups . First group was caudal epidural injection plus therapeutic exercise group , and the second group was NSAIDs plus therapeutic exercise group . Patients were assessed with 10 cm visual analogue scale for pain , straight leg raising test and Oswestry low back pain disability question naire at the beginning and at 15th day , 1st and 3rd month . RESULTS It was seen that both groups ' improvement were good and statistically significant . On the other h and , caudal epidural injection group 's improvement was better and faster than the NSAID group 's , and the differences between assessment scores of the groups were statistically significant , except the 3rd month Oswestry scores . CONCLUSION Finally , caudal epidural injection in the management of the subacute/chronic low back and radicular pain is a preferable choice , if applied by experienced specialists Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated . The largest group studied had low back pain with limited straight-leg raising ( SLR ) and in them the beneficial effect of manipulation in hastening pain relief was highly significant . In similar patients without limitation of SLR , the effect was of borderline significance . In all the other groups , treated patients also recovered more quickly than their controls . Traction , for patients with low back pain and sciatica , and epidural injections when a root palsy was present also produced some significant pain relief . The effect of sclerosants for back pain was less clear Study Design . A subgroup analysis of a prospect i ve , r and omized controlled trial was performed . Objective . To describe the cost effectiveness of periradicular infiltration with steroid in subgroups of patients with sciatica . Summary of Background Data . A recent trial on periradicular infiltration indicated that a methylprednisolone – bupivacaine combination had a short-term effect , as compared with that of saline . This report describes the efficacy and cost effectiveness of steroid in subgroups of patients with sciatic . Methods . This study involved 160 patients with unilateral sciatica . Outcome assessment s were leg pain ( 100-mm visual analog scale ) , disability on the Oswestry Low Back Disability Question naire , and the Nottingham Health Profile . Data on medical costs and sick leaves also were gathered . Patients were r and omized for periradicular infiltration with either methylprednisolone – bupivacaine or saline . The adjusted between-group treatment differences at each follow-up assessment , the number of patients free of leg pain ( responders , cutoff 75 % ) , and efficacy by the area-under-the-curve method were calculated . For the cost-effectiveness estimate , the total costs were divided by the number of responders . The rate of operations in different subgroups was evaluated by Kaplan-Meier analysis . Results . In the case of contained herniations , the steroid injection produced significant treatment effects and short-term efficacy in leg pain and in Nottingham Health Profile emotional reactions . For symptomatic lesions at L3–L4–L5 , steroid was superior to saline for leg pain , disability , and straight leg raising in the short term . By 1 year , steroid seemed to have prevented operations for contained herniations , costing $ 12,666 less per responder in the steroid group ( P < 0.01 ) . For extrusions , steroid seemed to increase the operation rate , and the steroid infiltration was more expensive , costing $ 4445 per responder ( P < 0.01 ) . Conclusions . In addition to short-term effectiveness for contained herniations and lesions at L3–L4–L5 , steroid treatment also prevented surgery for contained herniations . However , steroid was countereffective for extrusions . The results of the subgroup analyses call for a verification study Study Design . A r and omized , double-blind controlled trial . Objectives . To determine the treatment effect of corticosteroids in periradicular infiltration for chronic radicular pain . We also examined prognostic factors in relation to the outcome of the procedure . Summary of Background Data . Various studies have examined the therapeutic value of periradicular infiltration using treatment agents consisting of local anesthetic and corticosteroids for radicular pain , secondary to lumbar disc herniation and spinal stenosis . There is currently no r and omized trial to determine the efficacy of a single injection of corticosteroids for chronic radicular pain . Methods . Eligible patients with radicular pain who had unilateral symptoms who failed conservative management were r and omized for a single injection with bupivacaine and methylprednisolone or bupivacaine only . Outcome measures included the Oswestry Disability Index , visual analogue score for back pain and leg pain , claudication walking distance , and the patient 's subjective level of satisfaction of the outcome . Results . We recruited 43 patients in the bupivacaine and methylprednisolone group and 43 patients in the bupivacaine only group . The follow-up rate is 100 % . Five patients had early termination of the trial for discectomy and further root block . There is no statistically significant difference in the outcome measures between the groups at 3 months ( change of the Oswestry Disability Index [ P = 0.68 ] , change in visual analogue score [ back pain , P = 0.68 ; leg pain , P = 0.94 ] , change in walking distance [ P = 0.7 ] ) . Duration of symptoms has a statistically significant negative association with the change in Oswestry Disability Index ( P = 0.03 ) . Conclusion . Clinical improvement occurred in both groups of patients . Corticosteroids did not provide additional benefit UNLABELLED Epidural steroids are commonly administered in the treatment of " failed back surgery syndrome . " Because patient response is dependent on accurate steroid placement , fluoroscopic guidance has been advocated . However , because of ever-increasing medical expenditures , the cost-benefit of routine fluoroscopy should be critically evaluated . Therefore , 50 patients were enrolled into this institutional review board-approved , prospect i ve , controlled , single-blinded study . At a predetermined intervertebral level , the epidural space was identified using an air loss of resistance technique . Thereafter , an epidural catheter was inserted 2 cm through the epidural needle . To determine the accuracy of the clinical placement , contrast medium was administered through the epidural catheter ; antero-posterior and lateral lumbar spine radiographs were then obtained . The number of attempts required to successfully locate the epidural space , the reliability of the air loss of resistance technique in indicating successful epidural penetration in failed back surgery syndrome , the ability of the clinician to accurately predict the intervertebral space at which the epidural injection was performed , and the spread of contrast medium within the epidural space were recorded . A total of 48 epidurograms were performed . The number of attempts to successfully enter the epidural space was 2 + /- 1 . In 44 cases , the radiological studies confirmed the clinical impression that the epidural space had been successfully identified . In three patients , the epidural catheter was in the paravertebral tissue . One myelogram was recorded . In 25 patients , the epidural catheter did not pass through the predetermined intervertebral space . In 35 cases , the contrast medium did not reach the level of pathology . IMPLICATION S The clinical sign of loss of resistance is a reliable indicator of epidural space penetration in most cases of " failed back surgery syndrome . " However , surface anatomy is unreliable and may result in inaccurate steroid placement . Finally , despite accurate placement , the depot-steroid solution will spread to reach the level of pathology in only 26 % of cases Study Design . A r and omized single-blind clinical trial of facet injections plus exercise , versus exercise alone , in chronic disabling work-related lumbar spinal disorders ( CDWRLSD ) , accompanied by pilot interrater reliability and facet syndrome prevalence studies . Objectives . To systematic ally investigate the use of facet injections as an adjunct to supervised lumbar stretching exercises in regaining lumbar range of motion ( ROM ) following prolonged deconditioning after work-related lumbar injuries . To assess interrater reliability of visual assessment of segmental rigidity ( SR ) , and to evaluate the prevalence of facet syndrome in cases of lumbar SR . Summary of Background Data . Corticosteroid joint injections have often been used to reduce musculoskeletal inflammation to facilitate joint mobilization in the presence of degenerative arthritis . Lumbar segmental rigidity is a recently described entity usually associated with painful chronic spinal disorders and postoperative spine surgery . Previous work has shown that SR and lumbar ROM improves with a brief intervention consisting of facet injections followed by specific stretching exercises . No systematic study has investigated the potential benefits of a combination of facet injections and exercise over supervised exercises alone to treat lumbar SR . Similarly , no study has assessed the association between SR and the facet syndrome . Methods . From a group of consecutive patients ( n = 421 ) with CDWRLSD referred for tertiary rehabilitation between November 1999 and January 2001 , 70 were noted to have SR on intake physical examination . The first part of this study assessed interrater reliability for detecting SR , and intrarater reliability for 3-segment true lumbar ROM measurements . Patients r and omly assigned to participate in supervised stretching exercises with the addition of fluoroscopically guided bilateral facet injections at the involved levels ( Group A , n = 36 ) also underwent facet syndrome prevalence assessment at the time of injection . They were compared to a r and omly allocated comparison group ( Group B , n = 34 ) undergoing exercises alone in a single-blind design . Physical therapists saw patients an average of twice per week , providing supervision of a progressive home stretching program . Inclinometric joint ROM was measured at the time of group allocation , and again 5 to 7 weeks later . Vali date d question naires of pain ( intensity VAS ) and disability ( Million VAS ) related to the CDWRLSD were provided before and after the interventions . Results . Part 1 reliability and facet syndrome prevalence work revealed that interrater reliability for experienced examiners to detect rigid segments was excellent ( Pearson ’s r = 0.97 , P < 0.01 ) . Intrarater 3-joint motion measurement reliability was also good for all sagittal/coronal ROM ( Pearson ’s r = 0.95–0.99 , P < 0.01 ) . Only 5 of 29 subjects with SR met criteria for facet syndrome ( 17 % ) , consistent with prior prevalence studies of unselected patients with low back pain . In Part 2 , a large majority of patients in both groups improved from the initial to the post-treatment ROM measurements ( the primary outcome criterion of the study ) . However , a higher proportion of Group A ( injection ) patients ( 87%–95 % ) showed ROM improvement , compared to Group B ( exercise only ) patients ( 64%–79 % ) . Group A patients showed a significantly greater ROM improvement in all sagittal and coronal movements , both in absolute terms and percent of initial measurement . No significant differences in pain or disability self-report were found between groups , pre- or postintervention , but both groups showed significant improvement from pre- to postintervention in pain and disability assessment s. Conclusions . The detection of SR and measurement of 3-segment true lumbar ROM by experienced examiners is highly reliable . Only 17 % of CDWRLSD patients with lumbar SR met criteria for the facet syndrome , a rate approximately equal to that of unselected low back pain cohorts . This indicates that lumbar SR may be found whether or not pain of facet joint origin is present . In the r and omized trial , facet injections significantly increased the percentage of patients with SR showing ROM improvement , as well as the degree of improvement in lumbar mobility after treatment . There is no evidence that facet injections increase the improvements in pain/disability report noted in both groups Study Design . A r and omized , double-blind trial was conducted . Objectives . To test the efficacy of periradicular corticosteroid injection for sciatica . Summary of Background Data . The efficacy of epidural corticosteroids for sciatica is controversial . Periradicular infiltration is a targeted technique , but there are no r and omized controlled trials of its efficacy . Methods . In this study 160 consecutive , eligible patients with sciatica who had unilateral symptoms of 1 to 6 months duration , and who never underwent surgery were r and omized for double-blind injection with methylprednisolone bupivacaine combination or saline . Objective and self-reported outcome parameters and costs were recorded at baseline , at 2 and 4 weeks , at 3 and 6 months , and at 1 year . Results . Recovery was better in the steroid group at 2 weeks for leg pain ( P = 0.02 ) , straight leg raising ( P = 0.03 ) , lumbar flexion ( P = 0.05 ) , and patient satisfaction ( P = 0.03 ) . Back pain was significantly lower in the saline group at 3 and 6 months ( P = 0.03 and 0.002 , respectively ) , and leg pain at 6 months ( 13.5 , P = 0.02 ) . Sick leaves and medical costs were similar for both treatments , except for cost of therapy visits and drugs at 4 weeks , which were in favor of the steroid injection ( P = 0.05 and 0.005 , respectively ) . By 1 year , 18 patients in the steroid group and 15 in the saline group underwent surgery . Conclusions . Improvement during the follow-up period was found in both the methylprednisolone and saline groups . The combination of methylprednisolone and bupivacaine seems to have a short-term effect , but at 3 and 6 months , the steroid group seems to experience a “ rebound ” phenomenon BACKGROUND Tramadol and acetaminophen ( APAP ) have both shown efficacy in the treatment of lower back pain . The combination of these 2 agents has demonstrated synergistic analgesic action in animal models at specific ratios . OBJECTIVE This study assessed the long-term ( 3-month ) efficacy and safety of tramadol 37.5 mg/APAP 325 mg combination tablets in the treatment of chronic lower back pain . METHODS Patients with at least moderate lower back pain ( pain visual analog [ PVA ] score > /=40 mm on a 100-mm scale ) were r and omized to receive up to 8 tablets of tramadol/APAP per day or placebo for 91 days . Medication was titrated from 1 to 4 tablets/d by day 10 . The primary efficacy measure was PVA score at the final visit . Secondary measures included scores on the Pain Relief Rating Scale ( PRRS ) , Short-Form McGill Pain Question naire ( SF-MPQ ) , Rol and Disability Question naire ( RDQ ) , and 36-Item Short-Form Health Survey ( SF-36 ) ; the incidence of discontinuation due to insufficient pain relief ( Kaplan-Meier analysis ) ; and overall assessment s of medication by the patients and investigators . RESULTS Three hundred eighteen patients ( 161 tramadol/APAP , 157 placebo ) were included in the intent-to-treat population , defined as all patients who took > /=1 dose of study medication and had > /=1 postr and omization efficacy measurement . The mean age of the study population was 53.9 years , 63.2 % were female , 90.3 % were white , and the mean baseline PVA score was 70.0 mm . There were no significant differences between groups at baseline . Tramadol/APAP significantly improved final PVA scores ( P = 0.015 ) and final PRRS scores ( P < 0.001 ) compared with placebo . Tramadol/APAP also significantly improved RDQ scores ( P < /= 0.027 ) and scores on many subcategories of the SF-MPQ , including total score ( P = 0.021 ) . The tramadol/APAP group had significant improvements on the role-physical ( P = 0.005 ) , bodily pain ( P = 0.046 ) , role-emotional ( P = 0.001 ) , mental health ( P = 0.026 ) , reported health transition ( P = 0.038 ) , and mental component summary ( P = 0.008 ) subscales of the SF-36 . The cumulative incidence of discontinuation due to insufficient pain relief was 22.1 % for tramadol/APAP and 41.0 % for placebo ( P < 0.001 ) . Treatment-emergent adverse events in the tramadol/APAP group included nausea ( 13.0 % ) , somnolence ( 12.4 % ) , and constipation ( 11.2 % ) . CONCLUSIONS In this study , tramadol 37.5 mg/APAP 325 mg combination tablets were effective and had a favorable safety profile in the treatment of chronic lower back pain BACKGROUND The prevalence of persistent low back pain with the involvement of lumbar facet or zygapophysial joints has been described in controlled studies as varying from 15 % to 45 % based on the criteria of the International Association for the Study of Pain . Therapeutic interventions utilized in managing chronic low back pain of facet joint origin include intraarticular injections , medial branch nerve blocks , and neurolysis of medial branch nerves . OBJECTIVE To determine the clinical effectiveness of therapeutic lumbar facet joint nerve blocks in managing chronic low back pain of facet joint origin . DESIGN A prospect i ve , r and omized , double-blind trial . SETTING An interventional pain management setting in the United States . METHODS In this preliminary analysis , data from a total of 60 patients were included , with 15 patients in each of 4 groups . Thirty patients were in a non-steroid group consisting of Groups I ( control , with lumbar facet joint nerve blocks using bupivacaine ) and II ( with lumbar facet joint nerve blocks using bupivacaine and Sarapin ) ; another 30 patients were in a steroid group consisting of Groups III ( with lumbar facet joint nerve blocks using bupivacaine and steroids ) and IV ( with lumbar facet joint nerve blocks using bupivacaine , Sarapin , and steroids ) . All patients met the diagnostic criteria of lumbar facet joint pain by means of comparative , controlled diagnostic blocks . OUTCOME MEASURES Numeric Rating Scale ( NRS ) pain scale , the Oswestry Disability Index 2.0 ( ODI ) , employment status , and opioid intake . RESULTS Significant improvement in pain and functional status were observed at 3 months , 6 months , and 12 months , compared to baseline measurements . The average number of treatments for 1 year was 3.7 with no significant differences among the groups . Duration of average pain relief with each procedure was 14.8 + /- 7.9 weeks in the non-steroid group , and 12.5 + /- 3.3 weeks in the steroid group , with no significant differences among the groups . CONCLUSION Therapeutic lumbar facet joint nerve blocks with local anesthetic , with or without Sarapin or steroids , may be effective in the treatment of chronic low back pain of facet joint origin Study Design . A r and omized , open , long‐term , repeated‐dose comparison of an anti‐inflammatory drug and two opioid regimens in 36 patients with back pain . Objectives . To examine the long‐term safety and efficacy of chronic opioid therapy in a r and omized trial of patients with back pain . Methods . All participants underwent a 4‐week washout period of no opioid medication before being r and omly assigned to one of three treatment regimens for 16 weeks : 1 ) naproxen only , 2 ) set‐dose oxycodone , or 3 ) titrated‐dose oxycodone and sustained‐release morphine sulfate . All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks . Finally , all participants were monitored for a 1‐month posttreatment washout period . Each patient was called once a week for a report on pain , activity , mood , medication , hours awake , and adverse effects and was monitored carefully for signs of abuse and noncompliance . Results . Weekly reports during the experimental phase showed the titrated‐dose group to have less pain ( P < 0.001 ) and less emotional distress ( P < 0.001 ) than the other two groups . Both opioid groups were significantly different from the naproxen‐only group . During the titration phase , patients also reported significantly less pain and improved mood . Few differences were found in activity or hours asleep , or between average pretreatment and posttreatment phone‐interview and question naire variables . No adverse events occurred and only one participant showed signs of abuse behavior . Conclusions . The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep . Opioid therapy for chronic back pain was used without significant risk of abuse . However , tapered‐off opioid treatment is palliative and without long‐term benefit Study Design . R and omized single-blind controlled trial . Objective . We aim ed to compare the effects of epidural steroid injections and physical therapy program on pain and function in patients with lumbar spinal stenosis ( LSS ) . Summary of Background Data . LSS is one of the most common degenerative spinal disorders among elderly population . Initial treatment of this disabling painful condition is usually conservative including analgesics , nonsteroidal anti-inflammatory drugs , exercise , physical therapy , or epidural steroid injections . Owing to lack of sufficient data concerning the effectiveness of conservative treatment in LSS , we aim ed to compare the effectiveness of epidural steroid injections and physical therapy program in a r and omized controlled manner . Methods . A total of 29 patients diagnosed as LSS were r and omized into 3 groups . Group 1 ( n = 10 ) received an inpatient physical therapy program for 2 weeks , group 2 ( n = 10 ) received epidural steroid injections , and group 3 ( n = 9 ) served as the controls . All study patients additionally received diclofenac and a home-based exercise program . The patients were evaluated at baseline , 2 weeks , 1 month , 3 months , and 6 months after treatment by finger floor distance , treadmill walk test , sit-to-st and test , weight carrying test , Rol and Morris Disability Index , and Nottingham Health Profile . Results . Both epidural steroid and physical therapy groups have demonstrated significant improvement in pain and functional parameters and no significant difference was noted between the 2 treatment groups . Significant improvements were also noted in the control group . Pain and functional assessment scores ( RMDI , NHP physical activity subscore ) were significantly more improved in group 2 compared with controls at the second week . Conclusion . Epidural steroid injections and physical therapy both seem to be effective in LSS patients up to 6 months of follow-up CONTEXT Common pain conditions appear to have an adverse effect on work , but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain . OBJECTIVE To measure lost productive time ( absence and reduced performance due to common pain conditions ) during a 2-week period . DESIGN AND SETTING Cross-sectional study using survey data from the American Productivity Audit ( a telephone survey that uses the Work and Health Interview ) of working adults between August 1 , 2001 , and July 30 , 2002 . PARTICIPANTS R and om sample of 28 902 working adults in the United States . MAIN OUTCOME MEASURES Lost productive time due to common pain conditions ( arthritis , back , headache , and other musculoskeletal ) expressed in hours per worker per week and calculated in US dollars . RESULTS Thirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition . Headache was the most common ( 5.4 % ) pain condition result ing in lost productive time . It was followed by back pain ( 3.2 % ) , arthritis pain ( 2.0 % ) , and other musculoskeletal pain ( 2.0 % ) . Workers who experienced lost productive time from a pain condition lost a mean ( SE ) of 4.6 ( 0.09 ) h/wk . Workers who had a headache had a mean ( SE ) loss in productive time of 3.5 ( 0.1 ) h/wk . Workers who reported arthritis or back pain had mean ( SE ) lost productive times of 5.2 ( 0.25 ) h/wk . Other common pain conditions result ed in a mean ( SE ) loss in productive time of 5.5 ( 0.22 ) h/wk . Lost productive time from common pain conditions among active workers costs an estimated 61.2 billion dollars per year . The majority ( 76.6 % ) of the lost productive time was explained by reduced performance while at work and not work absence . CONCLUSIONS Pain is an inordinately common and disabling condition in the US workforce . Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance In this prospect i ve r and omized clinical trial , the results of epidural corticosteroid injections were evaluated in patients with lumbosciatic pain caused by herniated nucleus pulposus . Thirty-six patients with radicular lumbosciatic pain and positive straight leg raising test because of confirmed prolapsed intervertebral lumbar discs were r and omized into two groups with ( 17 patients ) and without ( 19 patients ) epidural corticosteroid injection . Members of the treatment groups received three injections of 100 mg methylprednisolone in 10 mL bupivacaine 0.25 % each . Additional therapy was st and ardized and identical in both groups . Followup examinations were performed at 2 weeks , 6 weeks , and 6 months . The examinations included pain level ( visual analogue scale ) , straight leg raising test , and functional status ( Hannover Functional Ability Question naire ) . At 2 weeks , patients receiving methylprednisolone injection showed a significant improvement in straight leg raising test results compared with patients in the control group . Results were better in the methylprednisolone group , although not statistically significant for pain relief and mobility . At 6 weeks and 6 months , pain relief , improvement of straight leg raising , and improvement of functional status showed no statistical significance . Epidural corticosteroid injections can be recommended as additional therapy only in the acute phase of the conservative management of lumbosciatic pain BACKGROUND Lumbar facet joints have been implicated as the source of chronic pain in 15 % to 45 % of patients with chronic low back pain . Various therapeutic techniques including intraarticular injections , medial branch blocks , and radiofrequency neurotomy of lumbar facet joint nerves have been described in the alleviation of chronic low back pain of facet joint origin . OBJECTIVE The study was conducted to determine the clinical effectiveness of therapeutic local anesthetic lumbar facet joint nerve blocks with or without steroid in managing chronic function-limiting low back pain of facet joint origin . DESIGN A r and omized , double-blind , controlled trial . SETTING An interventional pain management setting in the United States . METHODS This study included 60 patients in Group I with local anesthetic and 60 patients in Group II with local anesthetic and steroid . The inclusion criteria was based on the positive response to the diagnostic controlled comparative local anesthetic lumbar facet joint blocks . OUTCOME MEASURES Numeric pain scores , Oswestry Disability Index , opioid intake , and work status . All outcome assessment s were performed at baseline , 3 months , 6 months , and 12 months . RESULTS Significant improvement with significant pain relief ( > 50 % ) and functional improvement ( > 40 % ) were observed in 82 % and 85 % in Group I , with significant pain relief in over 82 % of the patients and improvement in functional status in 78 % of the patients . Based on the results of the present study , it appears that patients may experience significant pain relief 44 to 45 weeks of 1 year , requiring approximately 3 to 4 treatments with an average relief of 15 weeks per episode of treatment . CONCLUSION Therapeutic lumbar facet joint nerve blocks , with or without steroid , may provide a management option for chronic function-limiting low back pain of facet joint origin |
10,383 | 29,590,460 | Conclusions Available evidence indicates that coffee consumption is inversely associated with risk of T2D . | Context Type 2 diabetes ( T2D ) is a major health problem worldwide that is associated with increased morbidity and mortality .
There is increased interest in the value of different nutrition-based strategies for preventing the development of T2D .
Objective This review aims to cover current knowledge regarding the effects of coffee consumption on development of T2D or modulation of adverse complications .
A meta- analysis on coffee consumption and the risk of T2D was conducted . | The Nrf2/ARE pathway is a major cellular defense mechanism that prevents damage by reactive oxygen species through induction of antioxidative phase II enzymes . However , the activity of the Nrf2/ARE system is not uniform with variability in response presumed to be dependent on the Nrf2 genotype . We recently completed a pilot human coffee intervention trial with healthy humans , where large interindividual differences in the antioxidative response to the study coffee were examined . Here , we address the question whether differences in the modulation of Nrf2 gene transcription , assessed as an induction of Nrf2 gene transcription by Q-PCR , might be correlated with specific Nrf2 genotypes . To date , nine single nucleotide polymorphisms ( SNPs ) have been identified in the Nrf2 ( NFE2L2 ) gene . Two of these , the −617C/A and −651G/A SNPs are located within the promoter region and have previously been reported to influence the activity of the Nrf2/ARE pathway by reducing Nrf2 transcriptional activity . Sequencing of the critical Nrf2 gene promoter region not only confirmed the existence of these SNPs within the participants of the trial at the expected frequency ( 33 % carrying the −617C/A , 17 % the −651G/A and 56 % the −653A/G SNP ) but also indicated reduced Nrf2 gene transcription associated with a normal diet if the SNPs at position −617 , −651 or −653 were present . Of note , the data also indicated the study coffee increased Nrf2 gene transcription even in SNP carriers . This further highlights the relevance of genotype-dependent induction of Nrf2 gene transcription that appears to be largely influenced by dietary factors Background The relationship between coffee consumption and mortality in diverse European population s with variable coffee preparation methods is unclear . Objective To examine whether coffee consumption is associated with all-cause and cause-specific mortality . Design Prospect i ve cohort study . Setting 10 European countries . Participants 521 330 persons enrolled in EPIC ( European Prospect i ve Investigation into Cancer and Nutrition ) . Measurements Hazard ratios ( HRs ) and 95 % CIs estimated using multivariable Cox proportional hazards models . The association of coffee consumption with serum biomarkers of liver function , inflammation , and metabolic health was evaluated in the EPIC Biomarkers subcohort ( n = 14 800 ) . Results During a mean follow-up of 16.4 years , 41 693 deaths occurred . Compared with nonconsumers , participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality ( men : HR , 0.88 [ 95 % CI , 0.82 to 0.95 ] ; P for trend < 0.001 ; women : HR , 0.93 [ CI , 0.87 to 0.98 ] ; P for trend = 0.009 ) . Inverse associations were also observed for digestive disease mortality for men ( HR , 0.41 [ CI , 0.32 to 0.54 ] ; P for trend < 0.001 ) and women ( HR , 0.60 [ CI , 0.46 to 0.78 ] ; P for trend < 0.001 ) . Among women , there was a statistically significant inverse association of coffee drinking with circulatory disease mortality ( HR , 0.78 [ CI , 0.68 to 0.90 ] ; P for trend < 0.001 ) and cerebrovascular disease mortality ( HR , 0.70 [ CI , 0.55 to 0.90 ] ; P for trend = 0.002 ) and a positive association with ovarian cancer mortality ( HR , 1.31 [ CI , 1.07 to 1.61 ] ; P for trend = 0.015 ) . In the EPIC Biomarkers subcohort , higher coffee consumption was associated with lower serum alkaline phosphatase ; alanine aminotransferase ; aspartate aminotransferase ; γ-glutamyltransferase ; and , in women , C-reactive protein , lipoprotein(a ) , and glycated hemoglobin levels . Limitations Reverse causality may have biased the findings ; however , results did not differ after exclusion of participants who died within 8 years of baseline . Coffee-drinking habits were assessed only once . Conclusion Coffee drinking was associated with reduced risk for death from various causes . This relationship did not vary by country . Primary Funding Source European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer Recent results from prospect i ve cohort studies have shown that moderate coffee consumption is associated with a reduced risk for diabetes mellitus type II or Alzheimer 's disease . Since reactive oxygen species ( ROS ) are believed to be involved in the pathogenesis of these diseases , antioxidants in coffee might contribute to this risk reduction . We aim ed at elucidating whether a dark roast coffee beverage ( CB ) rich in N-methylpyridinium ions ( NMP : 785 μmol/L ) and low in chlorogenic acids ( CGA : 523 μmol/L ) has stronger antioxidant effects on human erythrocytes than a CB prepared from a light roast with opposite proportions ( CGA : 4538 μmol/L ; NMP : 56 μmol/L ) . Following a 2-wk wash out period , 500 mL of the respective CB was administered to 30 subjects daily for 4-wk . Blood and spot urine sample s were collected at the beginning and at the end of each intervention . Intake of the dark roast CB most effectively improved the antioxidant status of erythrocytes : superoxide dismutase and glutathione peroxidase activity decreased by 5.8 and 15 % , respectively , whereas tocopherol and total glutathione concentrations increased by 41 and 14 % , respectively . Furthermore , administration of the NMP-rich CB led to a significant body weight reduction in pre-obese subjects , whereas the CGA-rich CB did not BACKGROUND Coffee consumption has been associated with a lower risk of diabetes , but little is known about the mechanisms responsible for this association , especially related to the time when coffee is consumed . OBJECTIVE We examined the long-term effect of coffee , globally and according to the accompanying meal , and of tea , chicory , and caffeine on type 2 diabetes risk . DESIGN This was a prospect i ve cohort study including 69,532 French women , aged 41 - 72 y from the E3N/EPIC ( Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale/European Prospect i ve Investigation into Cancer and Nutrition ) cohort study , without diabetes at baseline . Food and drink intakes per meal were assessed by using a vali date d diet-history question naire in 1993 - 1995 . RESULTS During a mean follow-up of 11 y , 1415 new cases of diabetes were identified . In multivariable Cox regression models , the hazard ratio in the highest category of coffee consumption [ > or =3 cups ( 375 mL)/d ] was 0.73 ( 95 % CI : 0.61 , 0.87 ; P for trend < 0.001 ) , in comparison with no coffee consumption . This inverse association was restricted to coffee consumed at lunchtime ( hazard ratio : 0.66 ; 95 % CI : 0.57 , 0.76 ) when comparing > 1.1 cup ( 125 mL)/meal with no intake . At lunchtime , this inverse association was observed for both regular and decaffeinated coffee and for filtered and black coffee , with no effect of sweetening . Total caffeine intake was also associated with a statistically significantly lower risk of diabetes . Neither tea nor chicory consumption was associated with diabetes risk . CONCLUSIONS Our data support an inverse association between coffee consumption and diabetes and suggest that the time of drinking coffee plays a distinct role in glucose metabolism BACKGROUND Consumption of caffeinated beverages such as coffee and tea has been associated with a lower risk of type 2 diabetes ( T2D ) . Paradoxically , short-term metabolic studies have shown that caffeine impairs postpr and ial glycemic control . OBJECTIVE The objective was to prospect ively examine the association of caffeinated compared with caffeine-free beverages , including coffee , tea , sugar-sweetened beverages ( SSBs ) , and carbonated artificially sweetened beverages ( ASBs ) , with T2D risk . DESIGN We prospect ively observed 74,749 women from the Nurses ' Health Study ( NHS , 1984 - 2008 ) and 39,059 men from the Health Professionals Follow-Up Study ( HPFS , 1986 - 2008 ) who were free of diabetes , cardiovascular diseases , and cancer at baseline . RESULTS We documented 7370 incident cases of T2D during 24 y of follow-up in the NHS and 2865 new cases during 22 y of follow-up in the HPFS . After major lifestyle and dietary risk factors were controlled for , caffeinated and caffeine-free SSB intake was significantly associated with a higher risk of T2D in the NHS ( RR per serving : 13 % for caffeinated SSBs , 11 % for caffeine-free SSBs ; P < 0.05 ) and in the HPFS ( RR per serving : 16 % for caffeinated SSBs , 23 % for caffeine-free SSBs ; P < 0.01 ) . Only caffeine-free ASB intake in NHS participants was associated with a higher risk of T2D ( RR : 6 % per serving ; P < 0.001 ) . Conversely , the consumption of caffeinated and decaffeinated coffee was associated with a lower risk of T2D [ RR per serving : 8 % for both caffeinated and decaffeinated coffee in the NHS ( P < 0.0001 ) and 4 % for caffeinated and 7 % for decaffeinated coffee in the HPFS ( P < 0.01 ) ] . Only caffeinated tea was associated with a lower T2D risk among NHS participants ( RR per serving : 5 % ; P < 0.0001 ) . CONCLUSION Irrespective of the caffeine content , SSB intake was associated with a higher risk of T2D , and coffee intake was associated with a lower risk of T2D OBJECTIVE We evaluated the influence of coffee consumption on diabetes incidence among the Hawaii component of the Multiethnic Cohort ( MEC ) . DESIGN Prospect i ve cohort . SETTING Population -based sample residing in Hawaii . SUBJECTS After exclusions , 75 140 men and women of Caucasian , Japanese American and Native Hawaiian ancestry aged 45 - 75 years were part of the current analysis . All participants provided information on diet and lifestyle through an FFQ . After 14 years of follow-up 8582 incident diabetes cases were identified using self-reports , medication question naires and health plan linkages . Hazard ratios ( HR ) and 95 % confidence intervals were calculated using Cox regression while adjusting for known covariates . RESULTS The risk for diabetes associated with total coffee consumption differed by sex ( P interaction < 0·0001 ) . Women consuming ≥3 cups of any type of coffee daily had a significantly lower risk ( HR = 0·66 ; 95 % CI 0·58 , 0·77 ; P trend < 0·0001 ) than those reporting < 1 cup/d , whereas the relationship in men was borderline ( HR = 0·89 ; 95 % CI 0·80 , 0·99 ; P trend = 0·09 ) . The same difference by sex was seen for regular coffee consumption , with HR of 0·65 ( 95 % CI 0·54 , 0·78 ; P trend < 0·0001 ) and 0·86 ( 95 % CI 0·75 , 0·98 ; P trend = 0·09 ) in men and women , respectively . No significant association with diabetes was apparent for decaffeinated coffee in women ( HR = 0·85 ; 95 % CI 0·72 , 1·01 ; P trend = 0·73 ) or men ( HR = 1·07 ; 95 % CI 0·93 , 1·23 ; P trend = 0·71 ) . Despite small differences by ethnicity , the interaction terms between coffee intake and ethnicity were not significant . CONCLUSIONS In this multiethnic population , regular , but not decaffeinated , coffee intake was much more protective against diabetes in women of all ethnic groups than in men BACKGROUND The long-term effects of caffeine intake on weight have not been examined prospect ively . OBJECTIVE The objective was to assess the relation between caffeine intake and 12-y weight change . DESIGN We conducted a prospect i ve study of 18 417 men and 39 740 women , with no chronic diseases at baseline , who were followed from 1986 to 1998 . Caffeine intake was assessed repeatedly every 2 - 4 y. Weight change was calculated as the difference between the self-reported weight in 1986 and in 1998 . RESULTS The participants reported a change in caffeine intake that varied across quintiles , from decreases of 296 and 342 mg/d to increases of 213 and 143 mg/d in men and women , respectively . Age-adjusted models showed a lower mean weight gain in participants who increased their caffeine consumption than in those who decreased their consumption , but the differences between extreme quintiles were small : -0.43 kg ( 95 % CI : -0.17 , -0.69 ) in men and -0.41 kg ( 95 % CI : -0.20 , -0.62 ) in women . After adjustment for potential confounders and baseline and change in total energy intake and other nutrients and foods , the differences remained similar for men and diminished slightly for women ( men : -0.43 kg ; 95 % CI : -0.17 , -0.68 ; women : -0.35 ; 95 % CI : -0.14 , -0.56 ) . An increase in coffee and tea consumption was also associated with less weight gain . In men , the association between caffeine intake and weight was stronger in younger participants ( P for interaction < 0.001 ) ; in women , the association was stronger in those who had a body mass index ( in kg/m2 ) > or = 25 , who were less physically active , or who were current smokers ( P for interaction < 0.001 ) . CONCLUSION Increases in caffeine intake may lead to a small reduction in long-term weight gain BACKGROUND Increasing coffee intake was inversely associated with risk of type 2 diabetes in population s of European descent ; however , data from high-risk Asian population s are lacking as are data on tea intake in general . OBJECTIVE We investigated the prospect i ve associations between intakes of coffee , black tea , and green tea with the risk of type 2 diabetes in Singaporean Chinese men and women . DESIGN We analyzed data from 36 908 female and male participants in the Singapore Chinese Health Study aged 45 - 74 y in 1993 - 1998 who had multiple diet and lifestyle measures assessed and then were followed up between 1999 and 2004 . We used Cox regression models to investigate the association of baseline coffee and tea intakes with incident type 2 diabetes during follow-up , with adjustment for a number of possible confounding or mediating variables . RESULTS In multivariate models participants reporting > or = 4 cups of coffee/d had a 30 % reduction in risk of diabetes [ relative risk ( RR ) : 0.70 ; 95 % CI : 0.53 , 0.93 ] compared with participants who reported nondaily consumption . Participants reporting > or = 1 cup of black tea/d had a suggestive 14 % reduction in risk of diabetes ( RR : 0.86 ; 95 % CI : 0.74 , 1.00 ) compared with participants who reported 0 cups/d , and we observed no association with green tea . CONCLUSION Regular consumption of coffee and potentially black tea , but not green tea , is associated with lower risk of type 2 diabetes in Asian men and women in Singapore BACKGROUND Coffee is one of the most widely consumed beverages , but the association between coffee consumption and the risk of death remains unclear . METHODS We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health-AARP Diet and Health Study who were 50 to 71 years of age at baseline . Participants with cancer , heart disease , and stroke were excluded . Coffee consumption was assessed once at baseline . RESULTS During 5,148,760 person-years of follow-up between 1995 and 2008 , a total of 33,731 men and 18,784 women died . In age-adjusted models , the risk of death was increased among coffee drinkers . However , coffee drinkers were also more likely to smoke , and , after adjustment for tobacco-smoking status and other potential confounders , there was a significant inverse association between coffee consumption and mortality . Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows : 0.99 ( 95 % confidence interval [ CI ] , 0.95 to 1.04 ) for drinking less than 1 cup per day , 0.94 ( 95 % CI , 0.90 to 0.99 ) for 1 cup , 0.90 ( 95 % CI , 0.86 to 0.93 ) for 2 or 3 cups , 0.88 ( 95 % CI , 0.84 to 0.93 ) for 4 or 5 cups , and 0.90 ( 95 % CI , 0.85 to 0.96 ) for 6 or more cups of coffee per day ( P<0.001 for trend ) ; the respective hazard ratios among women were 1.01 ( 95 % CI , 0.96 to 1.07 ) , 0.95 ( 95 % CI , 0.90 to 1.01 ) , 0.87 ( 95 % CI , 0.83 to 0.92 ) , 0.84 ( 95 % CI , 0.79 to 0.90 ) , and 0.85 ( 95 % CI , 0.78 to 0.93 ) ( P<0.001 for trend ) . Inverse associations were observed for deaths due to heart disease , respiratory disease , stroke , injuries and accidents , diabetes , and infections , but not for deaths due to cancer . Results were similar in subgroups , including persons who had never smoked and persons who reported very good to excellent health at baseline . CONCLUSIONS In this large prospect i ve study , coffee consumption was inversely associated with total and cause-specific mortality . Whether this was a causal or associational finding can not be determined from our data . ( Funded by the Intramural Research Program of the National Institutes of Health , National Cancer Institute , Division of Cancer Epidemiology and Genetics . ) BACKGROUND Numerous studies have reported inverse associations of coffee , tea , and alcohol intake with risk of type 2 diabetes , but none has reported results separately among African American women . OBJECTIVE We prospect ively examined the relation of coffee , tea , and alcohol consumption to diabetes risk in African American women . DESIGN The study included 46,906 Black Women 's Health Study participants aged 30 - 69 y at baseline in 1995 . Dietary intake was assessed in 1995 and 2001 by using a vali date d food-frequency question naire . During 12 y of follow-up , there were 3671 incident cases of type 2 diabetes . Relative risks ( RRs ) and 95 % CIs were estimated by using Cox proportional hazards models adjusted for diabetes risk factors . RESULTS Multivariable RRs for intakes of 0 - 1 , 1 , 2 - 3 , and ≥4 cups of caffeinated coffee/d relative to no coffee intake were 0.94 ( 95 % CI : 0.86 , 1.04 ) , 0.90 ( 95 % CI : 0.81 , 1.01 ) , 0.82 ( 95 % CI : 0.72 , 0.93 ) , and 0.83 ( 95 % CI : 0.69 , 1.01 ) , respectively ( P for trend = 0.003 ) . Multivariable RRs for intakes of 1 - 3 , 4 - 6 , 7 - 13 , and ≥14 alcoholic drinks/wk relative to never consumption were 0.90 ( 95 % CI : 0.82 , 1.00 ) , 0.68 ( 95 % CI : 0.57 , 0.81 ) , 0.78 ( 95 % CI : 0.63 , 0.96 ) , and 0.72 ( 95 % CI : 0.53 , 0.98 ) , respectively ( P for trend < 0.0001 ) . Intakes of decaffeinated coffee and tea were not associated with risk of diabetes . CONCLUSION Our results suggest that African American women who drink moderate amounts of caffeinated coffee or alcohol have a reduced risk of type 2 diabetes BACKGROUND AND AIMS It was reported that high coffee consumption was related to decreased diabetes risk . The aim of this study is to examine the association between coffee consumption and the incidence of type 2 diabetes in persons with normal glucose tolerance in a population with a high incidence and prevalence of diabetes . METHODS AND RESULTS In a prospect i ve cohort study , information about daily coffee consumption was collected at the baseline examination ( 1989 - 1992 ) in a population -based sample of American Indian men and women 45 - 74 years of age . Participants with normal glucose tolerance ( N = 1141 ) at the baseline examination were followed for an average of 7.6 years . The incidence of diabetes was compared across the categories of daily coffee consumption . The hazard ratios of diabetes related to coffee consumption were calculated using Cox proportional hazards models , adjusted for potential confounders . Levels of coffee consumption were positively related to levels of current smoking and inversely related to body mass index , waist circumference , female gender , and hypertension . Compared to those who did not drink coffee , participants who drank 12 or more cups of coffee daily had 67 % less risk of developing diabetes during the follow-up ( hazard ratio : 0.33 , 95 % confidence interval : 0.13 , 0.81 ) . CONCLUSION In this population , a high level of coffee consumption was associated with a reduced risk of deterioration of glucose metabolism over an average 7.6 years of follow-up . More work is needed to underst and whether there is a plausible biological mechanism for this observation OBJECTIVE : To assess the effect of weight change on the relationship between coffee and tea consumption and diabetes risk . DESIGN : Prospect i ve cohort study , using data from the First National Health and Nutrition Examination Survey Epidemiologic Follow Up Study . Survival analyses were conducted using 301 selfreported cases of diabetes and eight documented diabetes deaths during an 8.4-y follow-up . SUBJECTS : A total of 7006 subjects aged 32–88 y with no reported history of diabetes were included in the study . RESULTS : For all subjects combined , increases in consumption of ground-caffeinated coffee and caffeine at baseline were followed by decreases in diabetes risk during follow-up . There were significant statistical interactions between age and consumption of caffeine ( P=0.02 ) and ground-caffeinated coffee ( P=0.03 ) . Age-stratified analysis showed that the decrease in diabetes risk only applied to ≤60-y-old subjects , for whom the decrease in diabetes risk also obtained for ground-decaffeinated coffee and regular tea . The multivariate hazard ratio ( HR ) and 95 % confidence interval for a 2 cups/day increment in the intake of ground-caffeinated coffee , ground-decaffeinated coffee and regular tea was 0.86 ( 0.75–0.99 ) , 0.58 ( 0.34–0.99 ) and 0.77 ( 0.59–1.00 ) , respectively . The diabetes risk was negatively related to the consumption in a dose – response manner . There were strong statistical interactions between prior weight change and beverage consumption for ≤60-y-old subjects . Further analysis revealed that the decrease in diabetes risk only applied to those who had lost weight , and that there was a positive dose – response relationship between diabetes risk and weight change . For example , the multivariate HR and 95 % confidence interval for > 0 vs 0 cups/day of ground-decaffeinated coffee was 0.17 ( 0.04–0.74 ) , 0.52 ( 0.19–1.42 ) , 0.77 ( 0.30–1.96 ) and 0.91 ( 0.39–2.14 ) for subgroups with weight change of ≤0 , 0–10 , 10–20 and > 20 lbs , respectively . There was no significant association between diabetes risk and consumption of instant-caffeinated coffee , instant-decaffeinated coffee or herbal tea . Caffeine intake appeared to explain some , but not all , of the diabetes-risk reduction and weight change . CONCLUSION : The negative relationship between diabetes risk and consumption of ground coffee and regular tea , observed for all NHEFS subjects , actually only applied to nonelderly adults who had previously lost weight Context Caffeine intake from coffee has been associated with a lower incidence of diabetes . Research ers have not studied the relationship of green tea , a popular beverage in Japan , where the incidence of diabetes is increasing rapidly . Contributions The authors estimated the intake of caffeine-containing beverages in a community-based survey in Japan and measured the 5-year incidence of diabetes . Greater intake of green tea or coffee was associated with a reduced incidence of diabetes . The effect of green tea was largely observed in women , was dose-related , and reflected caffeine intake . Implication s Higher intake of caffeine , whether from coffee or green tea , is associated with a lower incidence of diabetes . The Editors The prevalence of type 2 diabetes has increased worldwide , particularly in Asian countries where it was previously low ( 1 ) . In Japan , population -based studies have shown a 2-fold increase in the prevalence of diabetes during the past 2 decades , from 5 % to 10 % to 10 % to 15 % ( 2 ) . Several cohort studies done in Europe and in the United States reported an association between coffee consumption , a major source of caffeine , and reduced risk for diabetes ( 3 - 7 ) . Although these studies did not show any association between consumption of black tea and the risk for diabetes , they did not examine the effect of green or oolong teas , major sources of caffeine in Asian countries . Consumption of green tea is common in Japan ; 80 % of the population drinks green tea , and the average consumption per capita is 2 cups per day ( 8) . We wanted to determine whether there is a relationship between consumption of green tea and the risk for type 2 diabetes and , if so , whether caffeine fully accounts for this relationship . To examine these questions , we analyzed data from a large cohort study of 19487 middle-aged men and women in 25 communities across Japan . We also examined the effect of age , sex , body mass index ( BMI ) , family history , smoking status , alcohol use , magnesium intake , and physical activity on the association between this mode of caffeine consumption and risk for diabetes . Methods The Japan Collaborative Cohort Study for Evaluation of Cancer Risk ( JACC Study ) started between 1988 and 1990 . A total of 110792 individuals ( 46465 men and 64327 women ) who were 40 to 79 years of age and living in 45 communities across Japan participated in municipal health screening examinations and completed self-administered question naires regarding lifestyle and medical history of cardiovascular disease and cancer ( 9 ) . Informed consent was obtained before the completion of the question naire . Participants from 25 of the 45 communities completed 5-year follow-up surveys . Among 35690 participants ( 15177 men and 20513 women ) who were 40 to 65 years of age at baseline without a history of type 2 diabetes , stroke , coronary heart disease , or cancer , 17413 individuals ( 49 % ; 6727 men and 10686 women ) completed the 5-year follow-up question naire and provided valid responses on tea or coffee consumption and history of type 2 diabetes . The data from these 17413 individuals were used for the analyses . The mean age of the nonrespondents was 1 year younger for men ( 52.3 vs. 53.3 years of age ) and did not differ for women ( 53.1 vs. 53.0 years of age ) compared with the respondents . The mean BMI and the prevalence of a BMI of 25.0 kg/m2 or greater did not differ between the respondents and nonrespondents . Mean BMI was 22.7 kg/m2 versus 22.8 kg/m2 for men and 22.8 kg/m2 versus 22.9 kg/m2 for women , respectively ; the prevalence of overweight was 18 % versus 19 % for men and 21 % versus 22 % for women , respectively . The ethical committees at Nagoya University and the University of Tsukuba approved the study . Assessment of Consumption of Tea and Coffee and Caffeine Intake At baseline , consumption of tea and coffee was assessed by using a self-administered dietary question naire . Participants were asked to state their average consumption of green tea , black tea , oolong tea , and coffee during the previous year . They could select any of 4 frequency responses : less than once a week , about 1 to 2 times a week , about 3 to 4 times a week , and almost every day . Participants who selected the response of almost every day were also asked to state their average consumption of these beverages in number of cups per day . We classified the categories of consumption as less than 1 cup per week , 1 to 6 cups per week , 1 to 2 cups per day , 3 to 5 cups per day , and 6 or more cups per day . The highest 2 or 3 consumption categories were combined for coffee , black tea , and oolong tea because of the small number of participants in these categories . The consumption of decaffeinated coffee or tea was not recorded because these products were not commercially available in Japan in the early 1990s . The total intake of caffeine was calculated by adding the caffeine content from each specific beverage ( 1 cup for coffee or tea ) and multiplying it by the participant 's weight proportional to the frequency of caffeine use . We estimated the size of the cup for each beverage from a validation study ( 10 ) and the caffeine content per 100 mL of each beverage from the Japan Food Tables ( 11 ) . The estimated caffeine content was 153 mg per cup ( 170 mL ) of coffee , 30 mg per cup ( 200 mL ) of green tea , 51 mg per cup ( 170 mL ) of black tea , and 38 mg per cup ( 190 mL ) of oolong tea . The mean caffeine intake was 229 mg/d for men and 215 mg/d for women . Relative proportions of caffeine intake by beverage were 46 % from green tea , 44 % to 47 % from coffee , 3 % from black tea , and 4 % to 5 % from oolong tea . For reproducibility , the Spearman correlation coefficients between the 2 question naires , administered 1 year apart for 85 participants ( 8 men and 77 women ) , were 0.79 for green tea , 0.87 for coffee , 0.77 for black tea , and 0.56 for oolong tea ( 10 ) . The validity of the data was confirmed for the 85 participants by comparing the data from the question naire with those from four 3-day dietary records collected approximately 3 to 4 months apart ( 10 ) . The mean frequency of consumption of green tea was 25.4 cups per week according to the question naire and 30.1 cups per week according to four 1-week dietary records ( Spearman correlation coefficient , 0.47 ) . The respective mean frequencies were 8.0 cups and 7.1 cups per week with a correlation coefficient of 0.79 for coffee , 1.4 cups and 1.6 cups per week with a correlation coefficient of 0.70 for black tea , and 1.8 cups and 1.2 cups per week with a correlation coefficient of 0.55 for oolong tea . When we restricted the data to the 77 women , the results were essentially the same . Assessment of Diabetes Cases Participants who reported having diabetes newly diagnosed by physicians on the 5-year follow-up question naire were considered to have incident diabetes . To examine the validity of self-reporting of diabetes , we compared self-report data with laboratory findings and treatment status in a sample of 1230 men and 1837 women . We considered elevated glucose concentrations ( fasting serum glucose concentration 7.8 mmol/L [ 140 mg/dL ] or a r and omly measured concentration of 11.1 mmol/L [ 200 mg/dL ] ) or treatment with oral hypoglycemic agents or insulin to indicate new cases of diabetes . Recent criteria from the American Diabetes Association ( 12 ) were not used because the cases in our study were diagnosed before 1995 . The sensitivity of self-reporting was 70 % for men and 75 % for women ; the specificity was 95 % for men and 98 % for women . Statistical Analysis To examine potential confounding variables reported from previous studies ( 3 - 7 ) , we presented baseline characteristics according to the frequency of consumption for each beverage . Tests for trends were conducted by using the median values of confounding variables in each category of beverage ; the linear regression model was used for continuous variables , and the logistic regression model was used for categorical variables . The odds ratios for incident type 2 diabetes were calculated in each category of beverage consumption and in each quartile of caffeine intake ; less than 1 cup per week or the lowest quartile was used as the reference category . We estimated age , sex , and BMI -adjusted odds ratios and multivariable odds ratios using the logistic regression model , adjusting for age ( in years ) , sex , sex-specific quintiles of BMI ( weight in kilograms divided by the square of height in meters ) , parental history of diabetes ( yes or no ) , smoking status ( never , former , or current [ 1 to 19 , 20 to 29 , or 30 cigarettes/d ] ) , alcohol intake ( never , former , or current [ 1 to 22 , 23 to 45 , 46 to 68 , or 69 g/d ] ) , sex-specific quintiles of magnesium intake , hours of walking ( < 0.5 , 0.5 , 0.6 to 0.9 , and 1.0 h/d ) , and hours of participation in sports ( < 1 , 1 to 2 , 3 to 4 , and 5 h/wk ) . Sex-specific quintiles of BMI and magnesium intake were used because of different distributions between the sexes . We adjusted for magnesium intake because previous cohort studies indicated an inverse association between magnesium intake and risk for diabetes ( 13 , 14 ) . We conducted a test for trend by treating median values of each category of beverage or caffeine intake as continuous variables . We examined the association between caffeine intake and the risk for diabetes stratified by age group ( 40 to 54 years and 55 to 65 years ) , sex , family history of diabetes ( yes or no ) , current smoking status ( yes or no ) , current alcohol intake ( yes or no ) , magnesium intake ( below and above the sex-specific median ) , BMI ( < 25.0 kg/m2 and 25.0 kg/m2 ) , hours of walking ( < 0.5 and 0.5 h/d ) , and hours of participation in sports ( < 5 and 5 h/wk ) . The interactions with these stratified variables were tested by using cross-product terms of caffeine intake and the stratified variables . All analyses were conducted by using the SAS statistical package , version 8.2 ( SAS Institute Inc. , Cary , North Carolina ) . P values for statistical tests were 2-tailed , and 95 % CIs were estimated . Role of Background / Objectives : The purpose of this work was to investigate the association between coffee drinking and diabetes development and potential mediation by oxidative stress and inflammatory biomarkers . Subjects/ Methods : In 2001–2002 , a r and om sample of 1514 men ( 18–87 years old ) and 1528 women ( 18–89 years old ) were selected to participate in the ATTICA study ( Athens metropolitan area , Greece ) . A vali date d food-frequency question naire was used to assess coffee drinking ( abstention , casual , habitual ) and other lifestyle and dietary factors . Evaluation of oxidative stress and inflammatory markers was also performed . During 2011–2012 , the 10-year follow-up of the ATTICA study was carried out . The outcome of interest in this work was incidence of type 2 diabetes , defined according to American Diabetes Association criteria . Results : During follow-up , 191 incident cases of diabetes were documented ( incidence 13.4 % in men and 12.4 % in women ) . After various adjustments , individuals who consumed ⩾250 ml of coffee ( ≈1.5cup ) had 54 % lower odds of developing diabetes ( 95 % confidence interval : 0.24 , 0.90 ) , as compared with abstainers . A dose-response linear trend between coffee drinking and diabetes incidence was also observed ( P for trend=0.017 ) . When controlling for several oxidative stress and inflammatory biomarkers , the inverse association between habitual coffee drinking and diabetes was found to be mediated by serum amyloid-A levels . Conclusions : This work highlights the significance of long-term habitual coffee drinking against diabetes onset . The anti-inflammatory effect of several coffee components may be responsible for this protection Aims /hypothesisCoffee contains several substances that may affect glucose metabolism . The aim of this study was to evaluate the relationship between habitual coffee consumption and the incidence of IFG , IGT and type 2 diabetes . Methods We used cross-sectional and prospect i ve data from the population -based Hoorn Study , which included Dutch men and women aged 50–74 years . An OGTT was performed at baseline and after a mean follow-up period of 6.4 years . Associations were adjusted for potential confounders including BMI , cigarette smoking , physical activity , alcohol consumption and dietary factors . Results At baseline , a 5 cup per day higher coffee consumption was significantly associated with lower fasting insulin concentrations ( −5.6 % , 95 % CI −9.3 to −1.6 % ) and 2-h glucose concentrations ( −8.8 % , 95 % CI −11.8 to −5.6 % ) , but was not associated with lower fasting glucose concentrations ( −0.8 % , 95 % CI −2.1 to 0.6 % ) . In the prospect i ve analyses , the odds ratio ( OR ) for IGT was 0.59 ( 95 % CI 0.36–0.97 ) for 3–4 cups per day , 0.46 ( 95 % CI 0.26–0.81 ) for 5–6 cups per day , and 0.37 ( 95 % CI 0.16–0.84 ) for 7 or more cups per day , as compared with the corresponding values for the consumption of 2 or fewer cups of coffee per day ( p=0.001 for trend ) . Higher coffee consumption also tended to be associated with a lower incidence of type 2 diabetes ( OR 0.69 , CI 0.31–1.51 for ≥7 vs ≤2 cups per day , p=0.09 for trend ) , but was not associated with the incidence of IFG ( OR 1.35 , CI 0.80–2.27 for ≥7 vs ≤2 cups per day , p=0.49 for trend ) . Conclusions /interpretationOur findings indicate that habitual coffee consumption can reduce the risk of IGT , and affects post-load rather than fasting glucose metabolism CONTEXT Only a few studies of coffee consumption and diabetes mellitus ( DM ) have been reported , even though coffee is the most consumed beverage in the world . OBJECTIVE To determine the relationship between coffee consumption and the incidence of type 2 DM among Finnish individuals , who have the highest coffee consumption in the world . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve study from combined surveys conducted in 1982 , 1987 , and 1992 of 6974 Finnish men and 7655 women aged 35 to 64 years without history of stroke , coronary heart disease , or DM at baseline , with 175 682 person-years of follow-up . Coffee consumption and other study parameters were determined at baseline using st and ardized measurements . MAIN OUTCOME MEASURES Hazard ratios ( HRs ) for the incidence of type 2 DM were estimated for different levels of daily coffee consumption . RESULTS During a mean follow-up of 12 years , there were 381 incident cases of type 2 DM . After adjustment for confounding factors ( age , study year , body mass index , systolic blood pressure , education , occupational , commuting and leisure-time physical activity , alcohol and tea consumption , and smoking ) , the HRs of DM associated with the amount of coffee consumed daily ( 0 - 2 , 3 - 4 , 5 - 6 , 7 - 9 , > or = 10 cups ) were 1.00 , 0.71 ( 95 % confidence interval [ CI ] , 0.48 - 1.05 ) , 0.39 ( 95 % CI , 0.25 - 0.60 ) , 0.39 ( 95 % CI , 0.20 - 0.74 ) , and 0.21 ( 95 % CI , 0.06 - 0.69 ) ( P for trend<.001 ) in women , and 1.00 , 0.73 ( 95 % CI , 0.47 - 1.13 ) , 0.70 ( 95 % CI , 0.45 - 1.05 ) , 0.67 ( 95 % CI , 0.40 - 1.12 ) , and 0.45 ( 95 % CI , 0.25 - 0.81 ) ( P for trend = .12 ) in men , respectively . In both sexes combined , the multivariate-adjusted inverse association was significant ( P for trend < .001 ) and persisted when stratified by younger and older than 50 years ; smokers and never smokers ; healthy weight , overweight , and obese participants ; alcohol drinker and nondrinker ; and participants drinking filtered and nonfiltered coffee . CONCLUSION Coffee drinking has a grade d inverse association with the risk of type 2 DM ; however , the reasons for this risk reduction associated with coffee remain unclear OBJECTIVES To examine the long-term incidence of diabetes in relation to coffee consumption in Swedish women . DESIGN Prospect i ve longitudinal cohort study . SETTING City of Göteborg , Sweden . SUBJECTS A r and om population sample of 1361 women , aged 39 - 65 years , without prior diabetes or cardiovascular disease took part in a screening study in 1979 - 1981 with question naires , physical examination and blood sampling . MAIN OUTCOME MEASURES The development of diabetes until 1999 was identified by question naires in a second screening and the Swedish hospital discharge register . RESULTS Altogether , there were 74 new cases of diabetes . The risk of developing diabetes was 475 per 100 000 person-years in women who consumed two cups of coffee or less per day , 271 in women who consumed three to four cups per day , 202 with a consumption of five to six cups per day , and 267 in drinkers of seven cups or more per day . Associated hazard ratios , after adjustment for age , smoking , low physical activity , education and body mass index were 0.55 ( 0.32 - 0.95 ) , 0.39 ( 0.20 - 0.77 ) and 0.48 ( 0.22 - 1.06 ) for daily consumption of three to four , five to six and seven cups or more , respectively , with a consumption of less than two per day as reference . Additional adjustment for serum cholesterol and triglycerides attenuated the relation between coffee and diabetes slightly , indicating a possible mediating effect on the effect of coffee by serum lipids . CONCLUSIONS The findings of the present study support the hypothesis that coffee consumption protects from the development of diabetes in women OBJECTIVE Coffee consumption has been inversely associated with type 2 diabetes risk , but its mechanisms are largely unknown . We aim ed to examine whether plasma levels of sex hormones and sex hormone – binding globulin ( SHBG ) may account for the inverse association between coffee consumption and type 2 diabetes risk . RESEARCH DESIGN AND METHODS We conducted a case-control study nested in the prospect i ve Women 's Health Study ( WHS ) . During a median follow-up of 10 years , 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age , race , duration of follow-up , and time of blood draw . RESULTS Caffeinated coffee was positively associated with SHBG but not with sex hormones . Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming ≥4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers ( P for trend = 0.01 ) . In contrast , neither decaffeinated coffee nor tea was associated with SHBG or sex hormones . The multivariable-adjusted odds ratio ( OR ) of type 2 diabetes for women consuming ≥4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 ( 95 % CI 0.23–0.94 ; P for trend = 0.047 ) . The association was largely attenuated after further adjusting for SHBG ( OR 0.71 [ 95 % CI 0.31–1.61 ] ; P for trend = 0.47 ) . In addition , carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming ≥2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG . CONCLUSIONS Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women BACKGROUND Coffee consumption is associated with a decreased risk of type 2 diabetes . Suggested mechanisms underlying the association have included attenuation of sub clinical inflammation and a reduction in oxidative stress . OBJECTIVE The aim was to investigate the effects of daily coffee consumption on biomarkers of coffee intake , sub clinical inflammation , oxidative stress , glucose , and lipid metabolism . DESIGN Habitual coffee drinkers ( n = 47 ) refrained for 1 mo from coffee drinking ; in the second month they consumed 4 cups of filtered coffee/d and in the third month 8 cups of filtered coffee/d ( 150 mL/cup ) . Blood sample s were analyzed by gas chromatography-mass spectrometry , bead-based multiplex technology , enzyme-linked immunosorbent assay , or immunonephelometry . RESULTS Coffee consumption led to an increase in coffee-derived compounds , mainly serum caffeine , chlorogenic acid , and caffeic acid metabolites . Significant changes were also observed for serum concentrations of interleukin-18 , 8-isoprostane , and adiponectin ( medians : -8 % , -16 % , and 6 % , respectively ; consumption of 8 compared with 0 cups coffee/d ) . Serum concentrations of total cholesterol , HDL cholesterol , and apolipoprotein A-I increased significantly by 12 % , 7 % , and 4 % , respectively , whereas the ratios of LDL to HDL cholesterol and of apolipoprotein B to apolipoprotein A-I decreased significantly by 8 % and 9 % , respectively ( 8 compared with 0 cups coffee/d ) . No changes were seen for markers of glucose metabolism in an oral-glucose-tolerance test . CONCLUSIONS Coffee consumption appears to have beneficial effects on sub clinical inflammation and HDL cholesterol , whereas no changes in glucose metabolism were found in our study . Furthermore , many coffee-derived methylxanthines and caffeic acid metabolites appear to be useful as biomarkers of coffee intake OBJECTIVE To study prospect ively the association of coffee intake with incident diabetes in the Puerto Rico Heart Health Program cohort , comprising 9824 middle-aged men ( aged 35 - 79 years ) . METHODS Of 9824 men , 3869 did not provide a fasting blood sample at baseline , 1095 had prevalent diabetes and 131 were not given fasting glucose tests at any subsequent study visit . Thus , the present analysis includes 4685 participants . Diabetes was ascertained at baseline and at two study visits between 1968 and 1975 using fasting glucose tests and self-reports of physician-diagnosed diabetes or use of insulin or hypoglycaemic medication . Logistic regression analysis was used to assess the association of coffee intake with risk of incident diabetes while adjusting for covariates ( age , BMI , physical activity , smoking , education , alcohol intake , family history of diabetes , intakes of milk and sugar ) . RESULTS Five hundred and nineteen participants met the criteria for incident diabetes . Compared with those reporting intake of 1 - 2 servings of coffee/d , coffee abstainers were at reduced risk ( OR = 0.64 ; 95 % CI 0.43 , 0.94 ) . Among coffee drinkers , there was a significant trend of decreasing risk by intake ( P = 0.02 ) ; intake of > /=4 servings/d was associated with an odds ratio of 0.75 ( 95 % CI 0.58 , 0.97 ) . CONCLUSIONS Study findings support a protective effect of coffee intake on diabetes risk , while also suggesting that abstainers may be at reduced risk The results from a clinical study performed in 12 healthy volunteers with different coffee products containing glucose show that instant coffee enriched with chlorogenic acid induced a reduction in the absorption of glucose of 6.9 % compared with the control . No such effects were seen with normal or decaffeinated instant coffee . In a second , comparative , r and omized , double-blind , 12-week study we investigated the effect on the body mass of 30 overweight people , compared with normal instant coffee . The average losses in mass in the chlorogenic acid enriched and normal instant coffee groups were 5.4 and 1.7 kg , respectively . We conclude that chlorogenic acid enriched instant coffee appears to have a significant effect on the absorption and utilization of glucose from the diet . This effect , if the coffee is used for an extended time , may result in reduced body mass and body fat when compared with the use of normal instant coffee At least fourteen cohort studies have documented an inverse association between coffee consumption and risk of type 2 diabetes . We examined the prospect i ve association between coffee and tea consumption and the risk of type 2 diabetes mellitus among British men ( n 4055 ) and women ( n 1768 ) from the Whitehall II cohort . During 11.7 years follow-up there were a total of 387 incident cases of diabetes confirmed by self-report of doctor 's diagnosis or glucose tolerance tests . Despite an inverse association between coffee intake and 2 h post-load glucose concentration at the baseline assessment , combined caffeinated and decaffeinated coffee ( hazard ratio ( HR ) 0.80 ; 95 % CI 0.54 , 1.18 ) or only decaffeinated coffee intake ( HR 0.65 ; 95 % CI 0.36 , 1.16 ) was not significantly associated with diabetes risk at follow-up after adjustment for possible confounders . There was an association between tea intake and diabetes ( HR 0.66 ; 95 % CI 0.61 , 1.22 ; P < 0.05 ) after adjustment for age , gender , ethnicity and social status , which was not robust to further adjustments . There was , however , an association between combined intake of tea and coffee ( two or more cups per day of both beverage ) and diabetes ( HR 0.68 ; 95 % CI 0.46 , 0.99 ; P < 0.05 ) after full adjustment . In conclusion , relatively moderate intake ( more than three cups per day ) of coffee and tea were not prospect ively associated with incidence of type 2 diabetes although there was evidence of a combined effect . The limited range of exposure and beverage consumption according to socio-economic class may explain these conflicting findings Background Coffee consumption has been associated with a lower risk of type 2 diabetes in prospect i ve cohort studies , but the underlying mechanisms remain unclear . The aim of this study was to evaluate the effects of regular and decaffeinated coffee on biological risk factors for type 2 diabetes . Methods R and omized parallel-arm intervention conducted in 45 healthy overweight volunteers who were nonsmokers and regular coffee consumers . Participants were assigned to consumption of 5 cups ( 177 mL each ) per day of instant caffeinated coffee , decaffeinated coffee , or no coffee ( i.e. , water ) for 8 weeks . Results Average age was 40 years and body mass index was 29.5 kg/m2 . Compared with consuming no coffee , consumption of caffeinated coffee increased adiponectin ( difference in change from baseline 1.4 μg/mL ; 95 % CI : 0.2 , 2.7 ) and interleukin-6 ( difference : 60 % ; 95 % CI : 8 , 138 ) concentrations and consumption of decaffeinated coffee decreased fetuin-A concentrations ( difference : -20 % ; 95 % CI : -35 , -1 ) . For measures of glucose tolerance , insulin sensitivity , and insulin secretion , no significant differences were found between treatment groups . Conclusions Although no changes in glycemia and /or insulin sensitivity were observed after 8 weeks of coffee consumption , improvements in adipocyte and liver function as indicated by changes in adiponectin and fetuin-A concentrations may contribute to beneficial metabolic effects of long-term coffee consumption . Trial Registration clinical trials.gov Aims /hypothesisThe aim of this study was to examine the association of consumption of coffee and tea , separately and in total , with risk of type 2 diabetes and which factors mediate these relations . Methods This research was conducted as part of the Dutch Contribution to the European Prospect i ve Investigation into Cancer and Nutrition , which involves a prospect i ve cohort of 40,011 participants with a mean follow-up of 10 years . A vali date d food-frequency question naire was used to assess coffee and tea consumption and other lifestyle and dietary factors . The main outcome was verified incidence of type 2 diabetes . Blood pressure , caffeine , magnesium and potassium were examined as possible mediating factors . Results During follow-up , 918 incident cases of type 2 diabetes were documented . After adjustment for potential confounders , coffee and tea consumption were both inversely associated with type 2 diabetes , with hazard ratios of 0.77 ( 95 % CI 0.63–0.95 ) for 4.1–6.0 cups of coffee per day ( p for trend = 0.033 ) and 0.63 ( 95 % CI : 0.47–0.86 ) for > 5.0 cups of tea per day ( p for trend = 0.002 ) . Total daily consumption of at least three cups of coffee and /or tea reduced the risk of type 2 diabetes by approximately 42 % . Adjusting for blood pressure , magnesium , potassium and caffeine did not attenuate the associations . Conclusions /interpretationDrinking coffee or tea is associated with a lowered risk of type 2 diabetes , which can not be explained by magnesium , potassium , caffeine or blood pressure effects . Total consumption of at least three cups of coffee or tea per day may lower the risk of type 2 diabetes Abstract Purpose Coffee consumption has been reported to decrease oxidative damage in peripheral white blood cells ( WBC ) . However , effects on the level of spontaneous DNA str and breaks , a well established marker of health risk , have not been specifically reported yet . We analyzed the impact of consuming a dark roast coffee blend on the level of spontaneous DNA str and breaks . Methods Healthy men ( n = 84 ) were r and omized to consume daily for 4 weeks either 750 ml of fresh coffee brew or 750 ml of water , subsequent to a run in washout phase of 4 weeks . The study coffee was a blend providing high amounts of both caffeoylquinic acids ( 10.18 ± 0.33 mg/g ) and the roast product N-methylpyridinium ( 1.10 ± 0.05 mg/g ) . Before and after the coffee/water consumption phase , spontaneous str and breaks were determined by comet assay . Results At baseline , both groups exhibited a similar level of spontaneous DNA str and breaks . In the intervention phase , spontaneous DNA str and breaks slightly increased in the control ( water only ) group whereas they significantly decreased in the coffee group , leading to a 27 % difference within both arms ( p = 0.0002 ) . Food frequency question naires indicated no differences in the overall diet between groups , and mean body weight during the intervention phases remained stable . The consumption of the study coffee substantially lowered the level of spontaneous DNA str and breaks in WBC . Conclusion We conclude that regular coffee consumption contributes to DNA integrity BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects BACKGROUND Few studies have investigated the effect of dietary polyphenols on the complex human gut microbiota , and they focused mainly on single polyphenol molecules and select bacterial population s. OBJECTIVE The objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits . DESIGN Ten healthy male volunteers underwent a r and omized , crossover , controlled intervention study . After a washout period , all of the subjects received red wine , the equivalent amount of de-alcoholized red wine , or gin for 20 d each . Total fecal DNA was su bmi tted to polymerase chain reaction(PCR)-denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota . Several biochemical markers were measured . RESULTS The dominant bacterial composition did not remain constant over the different intake periods . Compared with baseline , the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus , Prevotella , Bacteroides , Bifidobacterium , Bacteroides uniformis , Eggerthella lenta , and Blautia coccoides-Eubacterium rectale groups ( P < 0.05 ) . In parallel , systolic and diastolic blood pressures and triglyceride , total cholesterol , HDL cholesterol , and C-reactive protein concentrations decreased significantly ( P < 0.05 ) . Moreover , changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number . CONCLUSION This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans , which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet . This trial was registered at controlled-trials.com as IS RCT N88720134 SCOPE Intervention studies provide evidence that long-term coffee consumption correlates with reduced DNA background damage in healthy volunteers . Here , we report on short-term kinetics of this effect , showing a rapid onset after normal coffee intake . METHODS AND RESULTS In a short-term human intervention study , we determined the effects of coffee intake on DNA integrity during 8 h. Healthy male subjects ingested coffee in 200 mL aliquots every second hour up to a total volume of 800 mL. Blood sample s were taken at baseline , immediately before the first coffee intake and subsequently every 2 h , prior to the respective coffee intake . DNA integrity was assayed by the comet assay . The results show a significant ( p < 0.05 ) reduction of background DNA str and breaks already 2 h after the first coffee intake . Continued coffee intake was associated with further decrements in background DNA damage within the 8 h intervention ( p < 0.01 and p < 0.001 , respectively ) . Mean tail intensities ( TIs% ) decreased from 0.33 TI% ( baseline , 0 h ) to 0.22 TI% ( within 8 h coffee consumption ) . CONCLUSION Repeated coffee consumption was associated with reduced background DNA str and breakage , clearly measurable as early as 2 h after first intake result ing in a cumulative overall reduction by about one-third of the baseline value OBJECTIVE High habitual coffee consumption has been associated with a lower risk of type 2 diabetes , but data on lower levels of consumption and on different types of coffee are sparse . RESEARCH DESIGN AND METHODS This is a prospect i ve cohort study including 88,259 U.S. women of the Nurses ' Health Study II aged 26 - 46 years without history of diabetes at baseline . Consumption of coffee and other caffeine-containing foods and drinks was assessed in 1991 , 1995 , and 1999 . We documented 1,263 incident cases of confirmed type 2 diabetes between 1991 and 2001 . RESULTS After adjustment for potential confounders , the relative risk of type 2 diabetes was 0.87 ( 95 % CI 0.73 - 1.03 ) for one cup per day , 0.58 ( 0.49 - 0.68 ) for two to three cups per day , and 0.53 ( 0.41 - 0.68 ) for four or more cups per day compared with nondrinkers ( P for trend < 0.0001 ) . Associations were similar for caffeinated ( 0.87 [ 0.83 - 0.91 ] for a one-cup increment per day ) and decaffeinated ( 0.81 [ 0.73 - 0.90 ] ) coffee and for filtered ( 0.86 [ 0.82 - 0.90 ] ) and instant ( 0.83 [ 0.74 - 0.93 ] ) coffee . Tea consumption was not substantially associated with risk of type 2 diabetes ( 0.88 [ 0.64 - 1.23 ] for four or more versus no cups per day ; P for trend = 0.81 ) . CONCLUSIONS These results suggest that moderate consumption of both caffeinated and decaffeinated coffee may lower risk of type 2 diabetes in younger and middle-aged women . Coffee constituents other than caffeine may affect the development of type 2 diabetes BACKGROUND Early studies suggested that coffee consumption may increase the risk of chronic disease . OBJECTIVE We investigated prospect ively the association between coffee consumption and the risk of chronic diseases , including type 2 diabetes ( T2D ) , myocardial infa rct ion ( MI ) , stroke , and cancer . DESIGN We used data from 42,659 participants in the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Germany study . Coffee consumption was assessed by self-administered food-frequency question naire at baseline , and data on medically verified incident chronic diseases were collected by active and passive follow-up procedures . HRs and 95 % CIs were calculated with multivariate Cox regression models and compared by competing risk analysis . RESULTS During 8.9 y of follow-up , we observed 1432 cases of T2D , 394 of MI , 310 of stroke , and 1801 of cancer as first qualifying events . Caffeinated ( HR : 0.94 ; 95 % CI : 0.84 , 1.05 ) or decaffeinated ( HR : 1.05 ; 95 % CI : 0.84 , 1.31 ) coffee consumption ( ≥4 cups/d compared with < 1 cup/d ; 1 cup was defined as 150 mL ) was not associated with the overall risk of chronic disease . A lower risk of T2D was associated with caffeinated ( HR : 0.77 ; 95 % CI : 0.63 , 0.94 ; P-trend 0.009 ) and decaffeinated ( HR : 0.70 ; 95 % CI : 0.46 , 1.06 ; P-trend : 0.043 ) coffee consumption ( ≥4 cups/d compared with < 1 cup/d ) , but cardiovascular disease and cancer risk were not . The competing risk analysis showed no significant differences between the risk associations of individual diseases . CONCLUSION Our findings suggest that coffee consumption does not increase the risk of chronic disease , but it may be linked to a lower risk of T2D IMPORTANCE Low-density lipoprotein cholesterol ( LDL-C ) is causally related to coronary artery disease ( CAD ) , but the relevance of high-density lipoprotein cholesterol ( HDL-C ) and triglycerides ( TGs ) is uncertain . Lowering of LDL-C levels by statin therapy modestly increases the risk of type 2 diabetes , but it is unknown whether this effect is specific to statins . OBJECTIVE To investigate the associations of 3 routinely measured lipid fractions with CAD and diabetes through mendelian r and omization ( MR ) using conventional MR and making use of newer approaches , such as multivariate MR and MR-Egger , that address the pleiotropy of genetic instruments where relevant . DESIGN , SETTING , AND PARTICIPANTS Published data from genome-wide association studies were used to construct genetic instruments and then applied to investigate associations between lipid fractions and the risk of CAD and diabetes using MR approaches that took into account pleiotropy of genetic instruments . The study was conducted from March 12 to December 31 , 2015 . MAIN OUTCOMES AND MEASURES Coronary artery disease and diabetes . RESULTS Genetic instruments composed of 130 single-nucleotide polymorphisms ( SNPs ) were used for LDL-C ( explaining 7.9 % of its variance ) , 140 SNPs for HDL-C ( 6.6 % of variance ) , and 140 SNPs for TGs ( 5.9 % of variance ) . A 1-SD genetically instrumented elevation in LDL-C levels ( equivalent to 38 mg/dL ) and TG levels ( equivalent to 89 mg/dL ) was associated with higher CAD risk ; odds ratios ( ORs ) were 1.68 ( 95 % CI , 1.51 - 1.87 ) for LDL-C and 1.28 ( 95 % CI , 1.13 - 1.45 ) for TGs . The corresponding OR for HDL-C ( equivalent to a 16-mg/dL increase ) was 0.95 ( 95 % CI , 0.85 - 1.06 ) . All 3 lipid traits were associated with a lower risk of type 2 diabetes . The ORs were 0.79 ( 95 % CI , 0.71 - 0.88 ) for LDL-C and 0.83 ( 95 % CI , 0.76 - 0.90 ) for HDL-C per 1-SD elevation . For TG , the MR estimates for diabetes were inconsistent , with MR-Egger giving an OR of 0.83 ( 95%CI , 0.72 - 0.95 ) per 1-SD elevation . CONCLUSIONS AND RELEVANCE Routinely measured lipid fractions exhibit contrasting associations with the risk of CAD and diabetes . Increased LDL-C , HDL-C , and possibly TG levels are associated with a lower risk of diabetes . This information will be relevant to the design of clinical trials of lipid-modifying agents , which should carefully monitor participants for dysglycemia and the incidence of diabetes BACKGROUND Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes , at least as long as the intervention continues . In the extended follow-up of the Finnish Diabetes Prevention Study , we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling . METHODS Overweight , middle-aged men ( n=172 ) and women ( n=350 ) with impaired glucose tolerance were r and omly assigned to intensive lifestyle intervention or control group . After a median of 4 years of active intervention period , participants who were still free of diabetes were further followed up for a median of 3 years , with median total follow-up of 7 years . Diabetes incidence , bodyweight , physical activity , and dietary intakes of fat , saturated fat , and fibre were measured . FINDINGS During the total follow-up , the incidence of type 2 diabetes was 4.3 and 7.4 per 100 person-years in the intervention and control group , respectively ( log-rank test p=0.0001 ) , indicating 43 % reduction in relative risk . The risk reduction was related to the success in achieving the intervention goals of weight loss , reduced intake of total and saturated fat and increased intake of dietary fibre , and increased physical activity . Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention , and the corresponding incidence rates during the post-intervention follow-up were 4.6 and 7.2 ( p=0.0401 ) , indicating 36 % reduction in relative risk . INTERPRETATION Lifestyle intervention in people at high risk for type 2 diabetes result ed in sustained lifestyle changes and a reduction in diabetes incidence , which remained after the individual lifestyle counselling was stopped BACKGROUND Although coffee consumption and tea consumption have been linked to diabetes , the relation with kidney function is less clear and is under research ed . OBJECTIVE We investigated the prospect i ve associations of coffee and tea consumption with estimated glomerular filtration rate ( eGFR ) . DESIGN We included 4722 participants aged 26 - 65 y from the Doetinchem Cohort Study who were examined every 5 y for 15 y. Coffee and tea consumption ( in cups/d ) were assessed at each round . eGFR was assessed by using the Chronic Kidney Disease Epidemiology Collaboration equation based on both plasma creatinine and cystatin C. We determined the association between categories of coffee and tea intake and 1 ) eGFR and 2 ) subsequent annual changes in eGFR by using generalized estimating equation analyses . RESULTS Baseline mean ± SD eGFR was 108.0 ± 14.7 mL · min(-1 ) · 1.73 m(-2 ) Tea consumption was not associated with eGFR . Those individuals who drank > 6 cups coffee/d had a 1.33 ( 95 % CI : 0.24 , 2.43 ) mL · min(-1 ) · 1.73 m(-2 ) higher eGFR than those who drank < 1 cup/d ( P-trend = 0.02 ) . This association was most apparent among those with a median age of ≥46 y at baseline , with eGFR being 2.47 ( 95 % CI : 0.42 , 4.51 ) mL · min(-1 ) · 1.73 m(-2 ) higher in participants drinking > 6 cups/d compared with < 1 cup/d ( P-trend = 0.02 ) . Adjustment for biological risk factors and coffee constituents did not attenuate the associations . Neither coffee nor tea consumption was associated with changes in eGFR . CONCLUSIONS Coffee consumption was associated with a slightly higher eGFR , particularly in those aged ≥46 y. The absence of an association with eGFR changes suggests that the higher eGFR among coffee consumers is unlikely to be a result of glomerular hyperfiltration . Therefore , low to moderate coffee consumption is not expected to be a concern for kidney health in the general population 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 An association between psychological factors and diabetes has been suspected for a long time . However , epidemiological data on this association is limited . We investigated the association between psychological factors ( perceived mental stress and type A behavior ) and the onset of diabetes in a community-based , prospect i ve cohort study in a large number of middle-aged Japanese adults . A total of 55,826 subjects ( 24,826 men and 31,000 women ) aged 40 - 69 years were followed for 10 years . A self-administered question naire on medical conditions including diabetes and other lifestyle factors was performed at baseline and 5 and 10 years later . Psychological factors and diabetes were assessed based on the question naire results . During the 10-year follow-up period , we documented 1,601 incident cases ( 6.4 % ) of diabetes among men and 1,093 cases ( 3.5 % ) among women . The risk of diabetes increased with an increasing stress level , especially among men . Multivariate adjusted odds ratios for high stress compared with low stress were 1.36 ( 1.13 to 1.63 ) among men and 1.22 ( 0.98 to 1.51 ) among women . The risk of diabetes increased with an increasing level of type A behavior only among women . Multivariate adjusted odds ratios for high levels of type A behavior compared with low levels of type A behavior were 1.09 ( 0.94 to 1.27 ) among men and 1.22 ( 1.01 to 1.47 ) among women . We found an association between perceived mental stress and the incidence of diabetes , especially among men . We also found an association between type A behavior and the incidence of diabetes among women . In addition , inverse association between coffee consumption and the incidence of diabetes which was consistent with other studies was observed The authors analyzed data from a prospect i ve , community-based cohort to assess the risk of incident type 2 diabetes mellitus associated with coffee and sweetened beverage consumption . They included 12,204 nondiabetic , middle-aged men and women in the Atherosclerosis Risk in Communities ( ARIC ) Study ( 1987 - 1999 ) . Consumption of each beverage was assessed by food frequency question naire and classified into categories of cups per day . They found an inverse association , after adjusting for potential confounders , between increased coffee consumption and risk of type 2 diabetes mellitus in men ( for > or = 4 cups ( > or = 0.95 liter)/day compared with almost never : hazard ratio = 0.77 , p(trend ) = 0.02 ) with no significant association in women ( hazard ratio = 0.89 , p(trend ) = 0.32 ) using a combination of self-report of physician-diagnosed diabetes , diabetes treatment , and a fasting or nonfasting blood glucose test . When self-reported diabetes or diabetes treatment alone was used , a stronger and significant inverse association was seen in men and women . Sweetened beverage consumption ( men : hazard ratio = 1.03 , p(trend ) = 0.94 ; women : hazard ratio = 1.01 , p(trend ) = 0.58 ) showed no consistent association with the incidence of type 2 diabetes mellitus . In summary , increased coffee consumption was significantly associated with a decreased risk of diagnosed type 2 diabetes mellitus in community-based US adults Background Coffee is widely consumed in the Western diet and therefore has important implication s for public health . Research findings pertaining to the effects of coffee consumption on cardiovascular health are conflicting , and the role of caffeine is not clear . Objective To examine the relationship between coffee intake , inflammation and cardiovascular function at baseline and during mental stress , both cross-sectionally and after a 4-week period of withdrawal of coffee during which intake of caffeine was maintained . Methods Eighty-five healthy , non-smoking men with varying coffee-drinking habits were recruited . Blood pressure , heart rate , and markers of inflammation [ C-reactive protein ( CRP ) , von Willebr and factor antigen ( vWF ) ] , were measured at baseline and during mental stress . These measures were repeated after a 4-week period of withdrawal of coffee , during which intake of caffeine was maintained . Habitual levels of coffee and caffeine consumption were assessed from a self-reported question naire , and saliva sample s for the analysis of caffeine concentrations were collected regularly throughout the period of withdrawal , to confirm compliance . Results Multiple linear regression analysis of pre-withdrawal data , adjusted for age , body mass index and intake of tea , red wine , fruit , vegetables , oily fish and dietary supplements revealed that coffee consumption was positively related to baseline systolic blood pressure , and increased heart rate and vWF responses to mental stress . Four weeks after withdrawal of coffee , the heightened vWF and heart rate responses to stress in habitual coffee drinkers persisted , whereas baseline systolic blood pressure had decreased . Total caffeine intake was unrelated to any measures of physiological function . Conclusions Habitual coffee consumption is associated with heightened acute vascular inflammatory responses to mental stress , although these effects are not affected by short-term abstinence from coffee . These findings suggest that the relationship between coffee and markers of cardiovascular risk may be explained by residual or unmeasured confounding factors Abstract Oral glucose tolerance tests were performed on 23 normal subjects and then repeated one week later . On one occasion , the test meal consisted of glucose dissolved in water and flavored with lemon juice ; on the other occasion , 5 Gm . of instant coffee were also added to the meal . The order of administration of the respective meals was r and omized . Serial blood sample s were obtained and analyzed for blood glucose concentration , serum free fatty acid levels and the serum immunoreactive insulin values . Paired comparisons of the data were made and the following results were obtained : ( 1 ) The subjects ingesting coffee plus glucose had significantly lower blood glucose levels 30 and 60 minutes postpr and ium than those consuming the glucose solution without coffee . ( 2 ) Three hours after ingestion of the test meal , the free fatty acid levels of the subjects receiving coffee with glucose were significantly higher than those receiving glucose without coffee . ( 3 ) No statistically significant differences between the two groups were found at any time period for the serum immunoreactive insulin levels . It is possible that coffee ingestion reduced the peak postpr and ial blood glucose levels by mobilizing a hormone from the gastrointestinal tract such as secretin , pancreozymin , or the newly discovered substance with glucagon-like immunoreactivity described by Unger et al 37 |
10,384 | 24,996,539 | There was no evidence of pain control additional to that provided by femoral nerve block .
Conclusions Local anaesthetic infiltration is effective in reducing short-term pain and hospital stay in patients receiving THR and TKR . | Background Surgical pain is managed with multi-modal anaesthesia in total hip replacement ( THR ) and total knee replacement ( TKR ) .
It is unclear whether including local anaesthetic infiltration before wound closure provides additional pain control . | Background Total hip or knee replacement is highly successful when judged by prosthesis-related outcomes . However , some people experience long-term pain . Objectives To review published studies in representative population s with total hip or knee replacement for the treatment of osteoarthritis reporting proportions of people by pain intensity . Data sources MEDLINE and EMBASE data bases search ed to January 2011 with no language restrictions . Citations of key articles in ISI Web of Science and reference lists were checked . Study eligibility criteria , participants and interventions Prospect i ve studies of consecutive , unselected osteoarthritis patients representative of the primary total hip or knee replacement population , with intensities of patient-centred pain measured after 3 months to 5-year follow-up . Study appraisal and synthesis methods Two authors screened titles and abstract s. Data extracted by one author were checked independently against original articles by a second . For each study , the authors summarised the proportions of people with different severities of pain in the operated joint . Results Search es identified 1308 articles of which 115 reported patient-centred pain outcomes . Fourteen articles describing 17 cohorts ( 6 with hip and 11 with knee replacement ) presented appropriate data on pain intensity . The proportion of people with an unfavourable long-term pain outcome in studies ranged from about 7 % to 23 % after hip and 10 % to 34 % after knee replacement . In the best quality studies , an unfavourable pain outcome was reported in 9 % or more of patients after hip and about 20 % of patients after knee replacement . Limitations Other studies reported mean values of pain outcomes . These and routine clinical studies are potential sources of relevant data . Conclusions and implication s of key findings After hip and knee replacement , a significant proportion of people have painful joints . There is an urgent need to improve general awareness of this possibility and to address determinants of good and bad outcomes Pain control is necessary for successful rehabilitation and outcome after total knee arthroplasty . Our goal was to compare the clinical efficacy of periarticular injections consisting of a long-acting local anesthetic ( ropivacaine ) and epinephrine with and without combinations of an α2-adrenergic agonist ( clonidine ) and /or a nonsteroidal anti-inflammatory agent ( ketorolac ) . In a double-blinded controlled study , we r and omized 160 patients undergoing total knee arthroplasty to receive 1 of 4 intraoperative periarticular injections : Group A , ropivacaine , epinephrine , ketorolac , and clonidine ; Group B , ropivacaine , epinephrine , and ketorolac ; Group C , ropivacaine , epinephrine , and clonidine ; Group D ( control ) , ropivacaine and epinephrine . Compared with Group D , Group A and B patients had significantly lower postoperative visual analog pain scores and nurse pain assessment and Group C patients had a significantly greater reduction in physical therapist pain assessment . We found no differences in other parameters analyzed Although the analgesic effects of periarticular multimodal drug injection ( PMDI ) after TKA have been well documented , there is little information about additional pain relieving effects of PMDI incorporated to contemporary multimodal pain control protocol s which have been proved to provide excellent analgesia . We performed a parallel-group , r and omised , controlled study to determine whether PMDI provides additional clinical benefits on contemporary multimodal analgesic protocol s including preemptive analgesics , continuous femoral nerve block , and IV-PCA . Eighty-seven patients were r and omized to a PMDI group ( n=45 ) or to a No-PMDI group ( n=42 ) . Pain level and opioid consumption were compared as primary outcomes . The incidences of narcotic and ropivacaine related side effects and complications , functional recovery , and satisfaction were also compared . The PMDI group experienced less pain during the operation night and the 1st postoperative day and showed lower opioid consumption over 24h after surgery . However , the PMDI group had a higher VAS pain score on the 1st postoperative day than during the operation night . No group differences in side-effects and complication incidences , functional recovery , and satisfaction were found . This study demonstrates that PMDI provides additional pain relief and reduces opioid consumption only during the early postoperative period in patients managed by the contemporary pain management protocol following TKA Background Several reports have confirmed the ability of intraoperative periarticular injections to control pain after THA . However , these studies used differing combinations of analgesic agents and the contribution of each , including the local anesthetic agent , is uncertain . Underst and ing the independent effects of the various agents could assist in improved pain management after surgery . Questions / purpose sWe therefore determined the ability of intraoperative periarticular infiltration of levobupivacaine to ( 1 ) reduce postoperative pain , ( 2 ) reduce postoperative morphine requirements , and ( 3 ) reduce the incidence of nausea and urinary retention . Patients and Methods A double-blinded , r and omized , placebo-controlled trial of patients undergoing primary THAs was performed . Patients were r and omized to receive a periarticular infiltration of 150 mg levobupivacaine in 60 mL 0.9 % saline ( n = 45 ) or a placebo consisting of 60 mL 0.9 % saline ( n = 46 ) . We obtained a short-form McGill pain score , visual analog scale ( VAS ) , and morphine requirements via patient-controlled analgesia ( PCA ) as primary measures . Postoperative antiemetic requirements and need for catheterization for urinary retention were determined as secondary measures . Results Subjectively reported pain scores and the overall intensity scores were similar for both groups in the postoperative period . At the same time the mean morphine consumption was less in the levobupivacaine group , most notable in the first 12 hours after surgery : treatment group 11.5 mg vs control group 21.2 mg . We observed no differences in the frequency of postoperative nausea and vomiting or urinary retention . Conclusions Our observations suggest periarticular injection of levobupivacaine can supplement available postoperative analgesic techniques and reduce postoperative morphine requirements after THA.Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Background and Objectives : High-volume local infiltration analgesia ( LIA ) is widely applied as part of a multimodal pain management strategy in total hip arthroplasty ( THA ) . However , method ological problems hinder the exact interpretation of previous trials , and the evidence for LIA in THA remains to be clarified . Therefore , we evaluated whether intraoperative high-volume LIA , in addition to a multimodal oral analgesic regimen , would further reduce acute postoperative pain after THA . Methods : Patients scheduled for unilateral , primary THA under spinal anesthesia were included in this r and omized , double-blind , placebo-controlled trial receiving high-volume ( 150 mL ) wound infiltration with ropivacaine 0.2 % with epinephrine ( 10 & mgr;g/mL ) or saline 0.9 % . A multimodal oral analgesic regimen consisting of slow-release acetaminophen 2 g , celecoxib 400 mg , and gabapentin 600 mg was instituted preoperatively . Rescue analgesic consisted of oral oxycodone . Pain was assessed repeatedly the first 8 hrs after surgery using the 100-mm visual analog scale . The primary end point was pain during walking ( 5 m ) 8 hrs after surgery . Secondary end points were pain at rest , pain on 45 degrees of passive flexion of the hip with the leg straight , and cumulative consumption of oxycodone . Results : A total of 120 patients were included . Pain during walking ( median [ interquartile range ] [ 95 % confidence interval ] ) was low in the ropivacaine versus the placebo group ( 20 [ 14 - 38 ] [ 0 - 93 ] vs 22 [ 10 - 40 ] [ 0 - 83 ] ) and did not differ significantly ( P = 0.71 ) . Consumption of rescue oxycodone ( 5 mg [ 0 - 10 mg ] [ 0 - 24 mg ] vs 10 mg [ 0 - 15 mg ] [ 0 - 29 mg ] ) did not differ ( P = 0.45 ) . Conclusions : Intraoperative high-volume LIA with ropivacaine 0.2 % provided no additional reduction in acute pain after THA when combined with a multimodal oral analgesic regimen consisting of acetaminophen , celecoxib , and gabapentin and is therefore not recommended This study tests the null hypothesis that there is no difference between sciatic nerve block ( SNB ) and periarticular anesthetic infiltration ( PI ) as adjuncts to femoral nerve blockade ( FNB ) in total knee arthroplasty in terms of postoperative opioid requirements . Fifty-two patients undergoing total knee arthroplasty were r and omized to receive either ( a ) combined FNB-SNB or ( b ) combined FNB-PI . Average morphine consumption in the first 24 ( 20 vs 23 mg ) and 48 hours ( 26 vs 33 mg ) showed no significant difference . Visual Analogue Scale scores , knee flexion ( 60 ° vs 67.5 ° ) and extension lag ( 0 ° vs 5 ° ) were comparable . Anesthetic time , surgical time , and length of hospital stay ( 5.5 vs 6 days ) were similar . This study showed no significant difference between the 2 groups . The PI offers a practical and potentially safer alternative to SNB Purpose Several analgesic techniques are available for pain management after a major operation . Material s and Methods From December 2005 to February 2006 , a prospect i ve , double-blind study was performed involving 90 patients who had undergone a total knee arthroplasty . Patients were r and omly divided into three equal groups ( n = 30 ) . Demographic data , including age , height , weight , knee score , visual analogue scale ( VAS ) , and range of flexion were evaluated preoperatively . Before wound closure , patients were given intra-synovial injections of the following solutions : patients in group I received 40 mL of 300 mg ropivacaine with 1 : 200,000 epinephrine and 5 mg morphine ; patients in Group II received 40 mL of 300 mg ropivacaine with epinephrine ; and patients in Group III received 50 mL normal saline as a control . All patients received an epidural patient-controlled analgesia ( PCA ) for 24 postoperative hours . Analgesic efficacy was evaluated using the VAS at intervals of 2 , 4 , 6 , 12 , 24 , 32 , 40 , and 48 hours postoperatively . During this period , the side effects , the dosage of rescue analgesia required , and the range of knee flexion were recorded for each group . Results There were no significant differences among the three groups with regards to the VAS and the required dose of rescue analgesia ( p > 0.05 ) . None of the groups demonstrated significant differences in the range of knee flexion and the incidence of postoperative nausea and emesis ( p > 0.05 ) . Conclusion Therefore , we found that ropivacaine , alone or with morphine , injected into the synovial tissue , along with an epidural PCA has no additional benefits in pain control after a total knee arthroplasty Background For the majority of patients with osteoarthritis ( OA ) , joint replacement is a successful intervention for relieving chronic joint pain . However , between 10 - 30 % of patients continue to experience chronic pain after joint replacement . Evidence suggests that a risk factor for chronic pain after joint replacement is the severity of acute post-operative pain . The aim of this r and omised controlled trial ( RCT ) is to determine if intra-operative local anaesthethic wound infiltration additional to a st and ard anaethesia regimen can reduce the severity of joint pain at 12-months after total knee replacement ( TKR ) and total hip replacement ( THR ) for OA . Methods 300 TKR patients and 300 THR patients are being recruited into this single-centre double-blind RCT . Participants are recruited before surgery and r and omised to either the st and ard care group or the intervention group . Participants and outcome assessors are blind to treatment allocation throughout the study . The intervention consists of an intra-operative local anaesthetic wound infiltration , consisting of 60 mls of 0.25 % bupivacaine with 1 in 200,000 adrenaline . Participants are assessed on the first 5 days post-operative , and then at 3-months , 6-months and 12-months . The primary outcome is the WOMAC Pain Scale , a vali date d measure of joint pain at 12-months . Secondary outcomes include pain severity during the in-patient stay , post-operative nausea and vomiting , satisfaction with pain relief , length of hospital stay , joint pain and disability , pain sensitivity , complications and cost-effectiveness . A nested qualitative study within the RCT will examine the acceptability and feasibility of the intervention for both patients and healthcare professionals . Discussion Large-scale RCTs assessing the effectiveness of a surgical intervention are uncommon , particulary in orthopaedics . The results from this trial will inform evidence -based recommendations for both short-term and long-term pain management after lower limb joint replacement . If a local anaesthetic wound infiltration is found to be an effective and cost-effective intervention , implementation into clinical practice could improve long-term pain outcomes for patients undergoing lower limb joint replacement . Trial registration Current Controlled Trials IS RCT Background Several previous surveys have estimated the rate of major complications that occur after regional anesthesia . However , because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques , re appraisal of the incidence and the characteristics of major complications is useful . Methods All French anesthesiologists were invited to participate in this 10-month prospect i ve survey based on ( 1 ) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts , and ( 2 ) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets . The service was free of charge for participants . Results The participants ( n = 487 ) reported 56 major complications in 158,083 regional anesthesia procedures performed ( 3.5/10,000 ) . Four deaths were reported . Cardiac arrest occurred after spinal anesthesia ( n = 10 ; 2.7/10,000 ) and posterior lumbar plexus block ( n = 1 ; 80/10,000 ) . Systemic local anesthetic toxicity consisted of seizures only , without cardiac toxicity . Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia ( 14.4/10,000 vs. 2.2/10,000 ) . Most neurologic complications were transient . Among 12 that occurred after peripheral nerve blocks , 9 occurred in patients in whom a nerve stimulator had been used . Conclusion This prospect i ve survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications Background Periarticular infiltration of local anesthetic , NSAIDs , and adrenaline have been reported to reduce postoperative pain , improve mobility , and reduce hospital stay for patients having THAs , but available studies have not determined whether local anesthetic infiltration alone achieves similar improvements . Questions We therefore asked whether periarticular injection of a local anesthetic during THA reduced postoperative pain and opioid requirements and improved postoperative mobility . Methods We r and omized 96 patients to either treatment ( n = 50 ) or control groups ( n = 46 ) . Before wound closure , the treatment group received local infiltration of 160 mL of levobupivacaine with adrenaline . The control group received no local infiltration . We assessed postoperative morphine consumption and pain during the 24 hours after surgery . Mobilization was assessed 24 hours postoperatively with supine-to-sit and sit-to-st and transfers , timed 10-m walk test , and timed stair ascent and descent . Patients and assessing physiotherapists were blind to study status . Result We observed no differences in postoperative morphine consumption , time to ascend and descend stairs , or ability to transfer between treatment and control groups . The treatment group reported more pain 7 to 12 hours postoperatively , but there were no differences in pain scores between groups at all other postoperative intervals . The treatment group showed increased postoperative walking speed greater than 6 m , but not greater than 10 m , compared with the control group . Conclusions Periarticular infiltration of local anesthetic during THA did not reduce postoperative pain or length of hospital stay and did not improve early postoperative mobilization . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence In this prospect i ve r and omized study , patients undergoing total hip ( THA ) or knee arthroplasty ( TKA ) were r and omized to either a study group receiving periarticular injections or a control group receiving patient-controlled analgesia with or without femoral nerve block ( TKA patients ) . All patients received a comprehensive multimodal perioperative protocol . Pain , recovery of functional milestones , and overall satisfaction were assessed . The THA study group demonstrated significantly lower average pain scores and higher overall satisfaction than the control group . There was no significant difference in pain scores between the study and control groups in the TKA cohort . Both study groups demonstrated lower narcotic usage and side effects as well as improved early functional recovery . Periarticular injection with a multimodal protocol was shown to safely provide excellent pain control and functional recovery and can be substituted for conventional pain control modalities BACKGROUND Postoperative analgesia with the use of parenteral opioids or epidural analgesia can be associated with troublesome side effects . Good perioperative analgesia facilitates rehabilitation , improves patient satisfaction , and may reduce the hospital stay . We investigated the analgesic effect of locally injected drugs around a total knee prosthesis . METHODS Sixty-four patients undergoing total knee arthroplasty were r and omized either to receive a periarticular intraoperative injection containing ropivacaine , ketorolac , epimorphine , and epinephrine or to receive no injection . The perioperative analgesic regimen was st and ardized . All patients in both groups received patient-controlled analgesia for twenty-four hours after the surgery , and this was followed by st and ard analgesia . Visual analog scores for pain , during activity and at rest , and for patient satisfaction were recorded preoperatively and postoperatively and at the six-week follow-up examination . The consumption of patient-controlled analgesia at specific postoperative time-points and the overall analgesic requirement were measured . RESULTS The patients who had received the injection used significantly less patient-controlled analgesia at six hours , at twelve hours , and over the first twenty-four hours after the surgery . In addition , they had higher visual analog scores for patient satisfaction and lower visual analog scores for pain during activity in the post-anesthetic-care unit and four hours after the operation . No cardiac or central nervous system toxicity was observed . CONCLUSIONS Intraoperative periarticular injection with multimodal drugs can significantly reduce the requirements for patient-controlled analgesia and improve patient satisfaction , with no apparent risks , following total knee arthroplasty Background The postoperative analgesic potential of periarticular anesthetic infiltration ( PAI ) after TKA is unclear as are the complications of continuous femoral nerve block on quadriceps function . Questions / purpose sWe asked ( 1 ) whether PAI provides equal or improved postoperative pain control in comparison to a femoral nerve block in patients who have undergone TKA ; and ( 2 ) if so , whether PAI improves early postoperative quadriceps control and facilitates rehabilitation . Methods We r and omized 60 patients to receive either PAI or femoral nerve block . During the first 5 days after TKA , we compared narcotic consumption , pain control , quadriceps function , walking distance , knee ROM , capacity to perform a straight leg raise , and active knee extension . Medication-related side effects , complications , operating room time , and hospitalization duration were compared . Results Opioid consumption was lower in the PAI group during the first 8 postoperative hours ( 12.5 mg versus 18.7 mg morphine ) , as was reported pain at rest ( 1.7 versus 3.5 on a 10-point VAS ) . Thereafter , narcotic consumption and reported pain were similar up to 120 hours . More subjects in the femoral nerve block group experienced quadriceps motor block ( 37 % versus 0 % in the PAI group ) . On Days 1 to 3 , subjects in the PAI group experienced better capacity to perform the straight leg raise , active knee extension , and had longer walking distances . Conclusions PAI provided pain control equivalent to that of a femoral nerve block while avoiding a motor block and its negative functional impacts . The data suggest it should be considered an alternative to a femoral nerve block . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence BACKGROUND Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain . The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence . METHODS Before st and ardized general anesthesia , 56 adult scheduled for major knee surgery were r and omly assigned to one of three groups , each to receive a different postoperative analgesic technique for 72 h : continuous epidural infusion , continuous femoral block , or intravenous patient-controlled morphine ( dose , 1 mg ; lockout interval , 7 min ; maximum dose , 30 mg/4 h ) . The first two techniques were performed using a solution of 1 % lidocaine , 0.03 mg/ml morphine , and 2 microg/ml clonidine administered at 0.1 ml x kg(-1 ) x h(-1 ) . Pain was assessed at rest and during continuous passive motion using a visual analog scale . The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon . To evaluate functional outcome , the maximal amplitudes were measured again on postoperative day 5 , at hospital discharge ( day 7 ) , and at 1- and 3-month follow-up examinations . When the patients left the surgical ward , they were admitted to a rehabilitation center , where their length of stay depended on prospect ively determined discharge criteria RESULTS The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group . The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group . On postoperative day 7 , these values were 90 degrees ( 60 - 100 degrees)(median and 25th-75th percentiles ) in the continuous epidural infusion group , 90 degrees ( 60 - 100 degrees ) in the continuous femoral block group , and 80 degrees ( 60 - 100 degrees ) in the patient-controlled morphine group ( P < 0.05 ) . The duration s of stay in the rehabilitation center were significantly shorter : 37 days ( range , 30 - 45 days ) in the continuous epidural infusion group , 40 days ( range , 31 - 60 days ) in the continuous femoral block group , and 50 days ( range , 30 - 80 days ) in the patient-controlled morphine group ( P < 0.05 ) . Side effects were encountered more frequently in the continuous epidural infusion group . CONCLUSION Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion , thereby hastening convalescence BACKGROUND Capacity to ambulate represents an important milestone in the recovery process after total knee arthroplasty ( TKA ) . The purpose of this study was to determine the analgesic effect of two analgesic techniques and their impact on functional walking capacity as a measure of surgical recovery . METHODS Forty ASA II-III subjects undergoing TKA were enrolled in a r and omized , double-blind , single-centre study receiving 48 h postoperative analgesia with either periarticular infiltration of local anaesthetic ( Group I ) or continuous femoral nerve block ( Group F ) . Breakthrough pain relief was achieved with patient-controlled analgesia ( PCA ) morphine . The main outcome was postoperative morphine consumption . Early ( postoperative days 1 - 3 ) and late ( 6 weeks ) functional walking capacity ( 2 and 6 min walk tests , 2MWT and 6MWT , respectively ) , degree of physical activity ( CHAMPS ) , health-related quality of life ( SF-12 ) , and clinical indicators of knee function ( WOMAC , Knee Society evaluation , and range of motion ) were measured . RESULTS Patients in Group F used the PCA less ( P=0.02 ) to achieve adequate analgesia . Postoperative 2MWT was similar in both groups ( P=0.27 ) . Six weeks after surgery , recovery of 6MWT , physical activity , and knee function were significantly improved in Group F ( P<0.05 ) . Preoperative walking capacity , physical activity and early total walking time were the independent predictors of early recovery . Distance and time spent walking were the predictors of functional walking exercise capacity at 6 weeks after surgery . CONCLUSIONS Femoral block is associated with lower opioid consumption and a better recovery at 6 weeks than periarticular infiltration . Early postoperative activity measures ( 2MWT and walking time ) were proved to be possible indicators of knee function recovery at 6 weeks after surgery BACKGROUND Postoperative pain after total hip arthroplasty ( THA ) can delay mobilization . This was assessed after intrathecal morphine ( ITM ) compared with local infiltration analgesia ( LIA ) using a non-inferiority design . METHODS Eighty patients were recruited in this r and omized , double-blind study . ITM 0.1 mg ( Group ITM ) or periarticular local anaesthetic ( ropivacaine 300 mg)+ketorolac 30 mg+ epinephrine 0.5 mg ( total volume 151.5 ml ) ( Group LIA ) were compared . After 24 h , 22 ml of saline ( Group ITM ) or ropivacaine ( 150 mg)+ketorolac ( 30 mg)+epinephrine ( 0.1 mg ) ( Group LIA ) were injected via a catheter . After operation , rescue analgesic consumption , pain intensity , and home-readiness were measured . RESULTS Morphine consumption was equivalent , median difference 0 mg ( 95 % confidence interval -4 to 4.5 ) between the groups at 0 - 24 h. During 24 - 48 h , it was lower in Group LIA ( 3 mg , 0 - 60 mg , median , range ) compared with Group ITM ( 10 mg , 0 - 81 mg ) ( P=0.01 ) . Lower pain scores were recorded at rest at 8 h in Group ITM ( P<0.01 ) , but in Group LIA on st and ing and mobilization , at 24 - 48 h ( P<0.01 ) . Paracetamol and tramadol consumption was lower in Group LIA ( P=0.05 and 0.05 , respectively ) as was pruritus , nausea , and vomiting ( P<0.05 ) . CONCLUSION Lower pain intensity was recorded early after surgery in ITM group but later , analgesic consumption , pain intensity on mobilization , and side-effects were lower in patients receiving LIA . LIA is a good alternative to ITM in patients undergoing THA BACKGROUND Recently , high-volume local infiltration analgesia ( LIA ) in total knee arthroplasty ( TKA ) has been introduced , but dosage , timing , and effects of adjuvants are still debated . METHODS We r and omized 102 patients undergoing TKA to receive either epidural analgesia ( EDA group ) or LIA ( ropivacaine 150 mg and epinephrine 0.5 mg ) combined with ketorolac 30 mg and morphine 5 mg given either locally ( LIA group ) or i.v . ( LIAiv group ) . Epidural analgesia was maintained for 48 h. Intra-articular re-injection via a catheter with ropivacaine 142.5 mg and either intra-articular or i.v . ketorolac 30 mg was given 24 h after surgery . Pain scores , morphine consumption , side-effects , and readiness for hospital discharge were studied . RESULTS At discharge from the postoperative anaesthetic care unit , verbal pain scores were lower in the EDA group ( P=0.004 ) , but discharge was delayed [ difference 101 min , 95 % CI : ( 23 , 178 ) , P=0.007 ] . Group LIA reported lower pain scores at rest beyond 24 h after surgery [ mean VAS ( sd ) at 24/48/72 h : LIA group 16/12/10 (14)/(13)/(11 ) ; LIAiv group 22/18/15 (17)/(15)/(12 ) ; EDA group 27/30/21 (21)/(29)/(19 ) ] . Both the LIA and the LIAiv groups were mobilized faster and were earlier ready for hospital discharge [ 3.5 days ( LIA group ) vs 4 days ( LIAiv group ) vs 5.5 days ( EDA group ) ; P<0.001 ] . Cumulated morphine consumption ( 72 h ) was lowest for the LIA group [ 80 vs 101 mg ( EDA group ) vs 118 mg ( LIAiv group ) , P=0.007 ] . CONCLUSIONS LIA with local adjuvants compared with epidural analgesia results in reduced opioid consumption , faster mobilization , and earlier readiness for hospital discharge . Ketorolac and morphine are more efficient when given locally than systemically . The study has been registered at clinical trials.gov ( NCT00562627 ) before onset of participant enrolment : http:// clinical trials.gov/ct2/show/NCT00562627?term=spreng&rank=2 ( April 21 , 2010 ) BACKGROUND Adequate postoperative analgesia with minimal side-effects is essential for early mobilization and recovery in patients undergoing total knee arthroplasty ( TKA ) . High-volume local infiltration analgesia ( LIA ) with ropivacaine has been introduced , but effects of adjuvants are still debated . We tested the hypothesis that the addition of ketorolac to LIA significantly improves analgesia after TKA . METHODS Sixty patients undergoing TKA were r and omized to receive intraoperative LIA ( ropivacaine 300 mg and epinephrine 0.5 mg ) combined with either ketorolac 30 mg ( ketorolac group ) or saline ( control group ) . After surgery , eight bolus doses of ropivacaine 100 mg combined with either ketorolac 15 mg ( ketorolac group ) or saline ( control group ) were administered every 6 h via an intra-articular catheter . The primary outcome was postoperative consumption of i.v . morphine patient-controlled analgesia ( PCA ) . Secondary outcomes were time to first request of i.v . morphine PCA , pain intensity , side-effects , and readiness for hospital discharge . RESULTS Consumption of i.v . morphine PCA was lower in the ketorolac group vs control group { 0 - 6 h : 0 ( 0 - 0 ) vs 5 ( 0 - 10 ) mg , P<0.0001 ; 0 - 48 h : 10 ( 0 - 22.5 ) vs 48.75 ( 30 - 82.5 ) mg , P<0.0001 [ median ( inter-quartile range , IQR)]}. Time to first request of i.v . morphine PCA was longer in the ketorolac group vs the control group [ 490 ( 248 - 617 ) vs 223 ( 115 - 319 ) min , P=0.02 , median ( IQR ) ] . Early postoperative pain ( < 48 h ) and readiness for hospital discharge were also significantly reduced in the ketorolac group . CONCLUSIONS LIA with ketorolac results in reduced morphine consumption , reduced pain intensity , and earlier readiness for hospital discharge Improvements in pain management techniques over the past decade have had a significant impact on the outcomes of total knee arthroplasty . Of these techniques , multimodal approaches have shown potential . The purpose of this study was to compare the results of periarticular injection ( PAI ) to a combination of patient-controlled epidural analgesia and femoral nerve block ( PCEA/FNB ) . Ninety patients undergoing primary unilateral total knee arthroplasty between June 2010 and March 2011 were r and omized into 2 groups . The first group received the PCEA/FNB protocol , whereas the second group received the PAI . Mean patient age was 66.1 ± 8.7 years . All patients were operated on using a similar st and ard medial parapatellar approach , and all received preemptive analgesia and postoperative pain protocol s. All patients were interviewed twice daily for the first 3 days postoperatively , once on day 7 , and once in month 6 . The 2 groups had similar readiness for discharge ( PCEA/FNB group , 3.3 ± 1.2 days ; PAI group , 3.2 ± 1.9 days ) . The results indicated no statistical difference between the 2 groups in 3 of 4 categories ( rest in the morning , rest in the evening , and ambulation in the morning ) . Pain on ambulation was the only category that was statistically lower in the PCEA/FNB group than in the PAI group . Although the study demonstrates similar results between the 2 groups , PAI can play a major role in postoperative pain control in institutions that may not have appropriately trained individuals , equipment , and re sources for PCEA/FNB . It also reduces many of the side effects and complications associated with regional anesthesia Background and purpose Postoperative pain is often severe after total knee arthroplasty ( TKA ) . We investigated the efficacy of the local infiltration analgesia ( LIA ) technique , both intraoperatively and postoperatively . Methods 48 patients undergoing TKA were r and omized into 2 groups in a double-blind study . In group A , 400 mg ropivacaine , 30 mg ketorolac , and 0.5 mg epinephrine were infiltrated periarticularly during operation . In group P , no injections were given . 21 h postoperatively , 200 mg ropivacaine , 30 mg ketorolac , and 0.1 mg epinephrine were injected intraarticularly in group A , and the same volume of saline was injected in group P. All patients were followed up for 3 months . Results Median morphine consumption was lower in group A during the first 48 h : 18 ( 1–74 ) mg vs. 87 ( 36–160 ) mg in group P. Postoperative pain was lower at rest in group A during the first 27 h , and on movement during the first 48 h , except at 21 h. Time to fulfillment of discharge criteria was shorter in group A than in group P : 3 ( 1–7 ) vs. 5 ( 2–8 ) days . Patient satisfaction was higher in group A than in group P on days 1 and 7 . The unbound venous blood concentration of ropivacaine was below systemic toxic blood concentrations . Interpretation The local infiltration analgesia ( LIA ) technique provides excellent pain relief and lower morphine consumption following TKA , result ing in shorter time to home readiness and higher patient satisfaction . There were few side effects and systemic LA concentrations were low Background and purpose Pain after total knee arthroplasty ( TKA ) is usually severe , and epidural analgesia or femoral nerve block has been considered to be an effective pain treatment . Recently , local infiltration analgesia ( LIA ) has become increasingly popular but the outcome of this method regarding the analgesic effect has not been fully evaluated . We compared local infiltration analgesia and femoral block with regard to analgesia and morphine dem and during the first 24 h after TKA . Methods 40 patients undergoing TKA under spinal anesthesia were r and omized to receive femoral nerve block ( group F ) or peri- and intraarticular infiltration analgesia ( group LIA ) with a mixture containing ropivacaine , ketorolac , and epinephrine . All patients had access to intravenous patient-controlled analgesia ( PCA ) with morphine postoperatively . Pain intensity at rest and upon movement was assessed on a numeric rating scale ( 0–10 ) on an hourly basis over 24 h if the patients were awake . Results The average pain at rest was marginally lower with LIA ( 1.6 ) than with femoral block ( 2.2 ) . Total morphine consumption per kg was similar between the 2 groups . Ancillary analysis revealed that 1 of 20 patients in the LIA group reported a pain intensity of > 7 upon movement , as compared to 7 out of 19 in the femoral block group ( p = 0.04 ) . Interpretation Both LIA and femoral block provide good analgesia after TKA . LIA may be considered to be superior to femoral block since it is cheaper and easier to perform Background This study evaluated the benefits and safety of a multimodal pain control protocol , which included a periarticular injection of local anesthetics , in patients undergoing total hip arthroplasty . Methods Between March 2006 and March 2007 , 60 patients undergoing unilateral total hip arthroplasty were r and omized to undergo either a multimodal pain control protocol or a conventional pain control protocol . The following parameters were compared : the preoperative and postoperative visual analogue scales ( VAS ) , hospital stay , operative time , postoperative rehabilitation , additional painkiller consumption , and complication rates . Results There was no difference between the groups in terms of diagnosis , age , gender , and BMI . Although both groups had similar VAS scores in the preoperative period and on the fifth postoperative day , there was a significant difference between the groups over the four-day period after surgery . There were no differences in the hospital stay , operative time , additional painkiller consumption , or complication rate between the groups . The average time for comfortable crutch ambulation was 2.8 days in the multimodal pain control protocol group and 5.3 days in the control group . Conclusions The multimodal pain control protocol can significantly reduce the level of postoperative pain and improve patients ' satisfaction , with no apparent risks , after total hip arthroplasty Background Postoperative pain after TKA is a major concern to patients . The best technique to control pain is still controversial . Intrathecal morphine or periarticular multimodal drug injection are both commonly used and both appear to provide better pain control than placebo , but it is unclear whether one or the other provides better pain control . Questions / purpose sWe asked whether intrathecal morphine or periarticular multimodal drug injection provides better pain control with fewer adverse events . Methods In a prospect i ve , double-blind , r and omized controlled trial we r and omized 57 patients with osteoarthritic knees who underwent TKAs into two groups . Group M ( n = 28 ) received 0.2 mg intrathecal morphine while Group I ( n = 29 ) received periarticular multimodal drug injection . Postoperative pain was managed with patient-controlled analgesia using ketorolac . The outcomes were pain levels , the amount of analgesic drug used , and drug-related side effects . Patients and evaluators were blinded . All patients were followed up to 3 months . Results We found no difference in postoperative pain level , analgesia drug consumption , blood loss in drain , and knee function . More patients in Group M required antiemetic ( 19 [ 69 % ] versus 10 [ 34 % ] ) and antipruritic drugs ( 10 [ 36 % ] versus three [ 10 % ] ) than patients in Group I. Conclusions The two techniques provide no different pain control capacity . The periarticular multimodal drug injection was associated with lower rates of vomiting and pruritus . Level of Evidence Level I , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence Background There have been few studies describing wound infiltration with additional intraarticular administration of multimodal analgesia for total knee arthroplasty ( TKA ) . In this study , we assessed the efficacy of wound infiltration combined with intraarticular regional analgesia with epidural infusion on analgesic requirements and postoperative pain after TKA . Methods 40 consecutive patients undergoing elective , primary TKA were r and omized into 2 groups to receive either ( 1 ) intraoperative wound infiltration with 150 mL ropivacaine ( 2 mg/mL ) , 1 mL ketorolac ( 30 mg/mL ) , and 0.5 mL epinephrine ( 1 mg/mL ) ( total volume 152 mL ) combined with intraarticular infusion ( 4 mL/h ) of 190 mL ropivacaine ( 2 mg/mL ) plus 2 mL ketorolac ( 30 mg/mL ) ( group A ) , or ( 2 ) epidural infusion ( 4 mL/h ) of 192 mL ropivacaine ( 2 mg/mL ) combined with 6 intravenous administrations of 0.5 mL ketorolac ( 30 mg/mL ) for 48 h postoperatively ( group E ) . For rescue analgesia , intravenous patient-controlled-analgesia ( PCA ) morphine was used . Morphine consumption , intensity of knee pain ( 0–100 mm visual analog scale ) , and side effects were recorded . Length of stay and corrected length of stay were also recorded ( the day- patients fulfilled discharge criteria ) . Results The median cumulated morphine consumption , pain scores at rest , and pain scores during mobilization were reduced in group A compared to group E. Corrected length of stay was reduced by 25 % in group A compared to group E. Interpretation Peri- and intraarticular analgesia with multimodal drugs provided superior pain relief and reduced morphine consumption compared with continuous epidural infusion with ropivacaine combined with intravenous ketorolac after TKA Background Epidural analgesia gives excellent pain relief but is associated with substantial side effects . We compared wound infiltration combined with intraarticular injection of local anesthetics for pain relief after total hip arthroplasty ( THA ) with the well-established practice of epidural infusion . Methods 80 patients undergoing elective THA under spinal block were r and omly assigned to receive either ( 1 ) continuous epidural infusion ( group E ) or ( 2 ) infiltration around the hip joint with a mixture of 100 mL ropivacaine 2 mg/mL , 1 mL ketorolac 30 mg/mL , and 1 mL epinephrine 0.5 mg/mL at the conclusion of surgery combined with one postoperative intraarticular injection of the same substances through an intraarticular catheter ( group A ) . Results Narcotic consumption was significantly reduced in group A compared to group E ( p = 0.004 ) . Pain levels at rest and during mobilization were similar in both groups but significantly reduced in group A after cessation of treatment . Length of stay was reduced by 2 days ( 36 % ) in group A compared to group E ( p < 0.001 ) . Interpretation Wound infiltration combined with 1 intraarticular injection can be recommended for patients undergoing THA . Further studies of dosage ( high/low ) and duration of intraarticular treatment are warranted Background Comfort and lack of pain are important for optimal mobilization after hip replacement . We investigated the efficacy of double wound infiltration . Patients and methods 40 consecutive patients undergoing total hip replacement were r and omized into two groups in this double-blinded study . They received wound infiltration at the end of surgery and through an intraarticular catheter 24 h postoperatively . The catheter was placed at the end of surgery . One group received solutions of ropivacaine , ketorolac , and adrenaline . Patients in the control group were injected with saline instead . The observation period was 6 weeks . Results The patients who received the analgesic solution had less pain up to 2 weeks postoperatively . They reached an earlier and lower pain minimum during the first days postoperatively , had lower use of analgesia up to day 4 postoperatively , and were more satisfied . Use of analgesic solution result ed in less joint stiffness and better function 1 week postoperatively . Interpretation Operative and postoperative wound infiltration with multimodal drugs reduces pain and the requirement for analgesics after hip replacement , leading to faster postoperative mobilization Eighty patients with osteoarthritis who underwent unilateral total knee arthroplasty were r and omly assigned to two groups : the trial group received an intraoperative intra-articular injection of magnesium sulphate and ropivacaine , and the control group received an injection of normal saline . All patients received patient-controlled analgesia with morphine for 48 h post-operatively . It was found that an intra-articular injection of magnesium sulphate and ropivacaine significantly reduced morphine consumption during the 0 - 24 h post-operative period and total 48-h postoperative morphine consumption . Pain scores at rest and during motion in the trial group were significantly lower than in the controls during the first 24 h post-operatively . The time to be able to perform a straight leg raise and to reach a 90 ° knee flexion was significantly shorter in the trial group compared with the controls . This study demonstrated that an intra-operative intra-articular magnesium sulphate and ropivacaine injection reduced the use of post-operative morphine Background Patient-controlled analgesia is a widely used and effective method of controlling pain after THA . This method is associated with substantial undesirable side effects . Local infiltration has been introduced in an attempt to reduce opioid requirements postoperatively , but its ability to reduce pain without complications is still question ed . Questions / Purpose sWe evaluated patient-controlled analgesia use , pain and satisfaction scores , complication rates , and ropivacaine levels associated with the use of periarticular multimodal drug infiltration in THA . Patients and Methods We r and omized 64 patients undergoing THA to receive a periarticular intraoperative multimodal drug injection or to receive no injection . All patients received patient-controlled analgesia for 24 hours after surgery . The final assessment was at 6 weeks . Results Patients receiving the periarticular injection used less patient-controlled analgesia 6 hours postoperatively . The 24-hour patient-controlled analgesia requirement postsurgery also was less . The visual analog scale score for pain on activity in the postanesthetic care unit was less for patients who received an injection . The visual analog scale satisfaction score was similar in the two groups throughout the followup period . Recorded unbound ropivacaine levels were 2.5 times lower than toxic levels . Conclusions Periarticular intraoperative injection with multimodal drugs can reduce postoperative patient-controlled analgesia requirements and pain on activity in patients undergoing THA with no apparent increase in risk . Level of Evidence Level I , therapeutic study . See the guidelines online for a complete description of level of evidence Background Postoperative pain after total knee arthroplasty ( TKA ) can be difficult to manage and may delay recovery . Recent studies have suggested that periarticular infiltration with local anesthetics may improve outcome . Methods 80 patients undergoing TKA under spinal anesthesia were r and omized to receive continuous femoral nerve block ( group F ) or peri- and intraarticular infiltration and injection ( group I ) . Group I received a solution of 300 mg ropivacaine , 30 mg ketorolac , and 0.5 mg epinephrine by infiltration of the knee at the end of surgery , and 2 postoperative injections of these substances through an intraarticular catheter . Results More patients in group I than in group F could walk < 3 m on the first postoperative day ( 29/39 vs. 7/37 , p < 0.001 ) . Group I also had significantly lower pain scores during activity and lower consumption of opioids on the first postoperative day . No differences between groups were seen regarding side effects or length of stay . Interpretation Peri- and intraarticular application of analgesics by infiltration and bolus injections can improve early analgesia and mobilization for patients undergoing TKA . Further studies of optimal drugs , dosage , and duration of this treatment are warranted OBJECTIVE Postoperative pain after total hip arthroplasty ( THA ) is not well tolerated . We assessed postoperative pain relief and the need for opioid use after using a cocktail of local and intraarticular analgesic injection ( LIA ) after THA . METHODS Eighty patients undergoing THA under spinal anesthesia were r and omly assigned to receive either LIA or placebo . The LIA was composed of 5 mg morphine , 30 mg bupivacaine ( 15 mg/1.5 mL ) , 1 mL betamethasone , and 0.5 mL epinephrine ( 1:1,000 ) intraoperatively . We compared three outcomes total morphine consumption , visual analog scale ( VAS ) at rest and during activity , and hip flexion angle while st and ing . RESULTS When compared with placebo , opioid consumption was significantly reduced in the trial group , as well as VAS at rest and during mobilization . Earlier rehabilitation and better range of motion ( ROM ) were achieved in the trial group . There were no significant differences in side effects or postoperative wound healing between groups . CONCLUSION In patients undergoing THA , LIA may reduce postoperative systemic opioid use and offer better pain control and earlier rehabilitation , without observable risks OBJECTIVE Find out if the addition of periarticular local anesthetic infiltration enhances the quality of postoperative pain control in patients with knee arthroplasty ( TKA ) in spinal anesthesia and intrathecal morphine plus single shot femoral nerve block ( FNB ) . MATERIAL AND METHOD . Ninety-nine patients scheduled for TKA under spinal anesthesia were enrolled after written informed consent , and r and omized into two groups with either periarticular injection of 20 ml 0.25 % bupivacaine ( B-gr n = 50 ) or isotonic saline solution ( S-gr n = 49 ) . All patients had intrathecal morphine 0.2 mg and single shot FNB with 20 ml bupivacaine 0.25 % and were adjusted postoperative analgesic requirement via patient controlled analgesia with morphine . Effect of postoperative pain control and requirement of additional analgesics were recorded . RESULTS R and omization created comparable groups . Periarticular infiltration of bupivacaine in addition to femoral nerve block and intrathecal morphine was efficient and superior to saline regarding pain control , morphine consumption , and patient 's satisfaction . More patients in B-gr did not require any supplement morphine in the first 24 hours ( 26 % compared to 12.2 % , p < or = 0.01 ) . In patients who required morphine , B-gr had longer pain free period ( 25 hours compared to 14.8 hours , p < 0.001 ) and needed lower dose of morphine ( 5.16 mg compared to 8 . 67 mg , p = 0.005 ) . No significant side effects were recorded . CONCLUSION Adding periarticular infiltration to femoral block and intrathecal morphine significantly enhances the quality of postoperative pain therapy in TKA patients . However combining three methods for analgesic therapy may be too much effort . Modifying infiltration techniques including continuous application needs further research Purpose Epidural and intravenous patient-controlled analgesia ( PCA ) are established methods for pain relief after total hip arthroplasty ( THA ) . Periarticular infiltration is an alternative method that is gaining ground due to its simplicity and safety . Our study aims to assess the efficacy of periarticular infiltration in pain relief after THA . Methods Sixty-three patients undergoing THA under spinal anaesthesia were r and omly assigned to receive postoperative analgesia with continuous epidural infusion with ropivacaine ( epidural group ) , intraoperative periarticular infiltration with ropivacaine , clonidine , morphine , epinephrine and corticosteroids ( infiltration group ) or PCA with morphine ( PCA group ) . PCA morphine provided rescue analgesia in all groups . We recorded morphine consumption , visual analog scale ( VAS ) scores at rest and movement , blood loss from wound drainage , mean arterial pressure ( MAP ) and adverse effects at 1 , 6 , 12 , 24 h postoperatively . Results Morphine consumption at all time points , VAS scores at rest , 6 , 12 and 24 h and at movement , 6 and 12 h postoperatively were lower in infiltration group compared to PCA group ( p < 0.05 ) , but did not differ between infiltration and epidural group . There was no difference in adverse events in all groups . At 24 h , MAP was higher in the PCA group ( p < 0.05 ) and blood loss was lower in the infiltration group ( p < 0.05 ) . Conclusions In our study periarticular infiltration was clearly superior to PCA with morphine after THA , providing better pain relief and lower opioid consumption postoperatively . Infiltration seems to be equally effective to epidural analgesia without having the potential side effects of the latter BACKGROUND As continuous wound instillation with local anaesthetic has not been evaluated after hip/knee arthroplasties , our study was design ed to determine whether this technique could enhance analgesia and improve patient outcome after joint replacement surgery . METHODS Thirty-seven patients undergoing elective hip/knee arthroplasties under spinal block were r and omly assigned to two analgesia groups . Group M received continuous i.v . infusion of morphine plus ketorolac for 24 h. Then , a multi-hole 16 G catheter was placed subcutaneously and infusion of saline was maintained for 55 h. Group R received i.v . saline . Thereafter the wound was infiltrated with a solution of ropivacaine 0.5 % 40 ml , then a multi-hole 16 G catheter was placed subcutaneously and an infusion of ropivacaine 0.2 % 5 ml h(-1 ) was maintained for 55 h. Visual analogue scale scores were assessed at rest and on passive mobilization by nurses blinded to analgesic treatment . Total plasma ropivacaine concentration was measured . RESULTS Group R showed a significant reduction in postoperative pain at rest and on mobilization , while rescue medication requirements were greater in Group M. Total ropivacaine plasma concentration remained below toxic concentrations and no adverse effects occurred . Length of hospital stay was shorter in Group R. CONCLUSION Infiltration and wound instillation with ropivacaine 0.2 % is more effective in controlling postoperative pain than systemic analgesia after major joint replacement surgery BACKGROUND : In this study , we investigated the impact of a continuous wound infusion with ropivacaine 0.3 % on pain and morphine consumption after minimally invasive hip arthroplasty . METHODS : Seventy-six consecutive patients scheduled for elective minimally invasive hip replacement using spinal anesthesia were prospect ively included in this double-blind study . Epicapsular placement of a 15-cm fenestrated catheter was performed by the surgeon . Patients were r and omized to receive either 20 mL ropivacaine 0.3 % ( R-group ) or 20 mL NaCl 0.9 % ( P-group ) applied into the wound as a bolus before wound closure . A continuous infusion of either ropivacaine 0.3 % or placebo was then infused at 8 mL/h for 48 hours after surgery with an elastomeric pump . Morphine IV-patient-controlled analgesia was offered to all patients . Morphine consumption , pain at rest and with motion , and total and unbound ropivacaine plasma concentration were recorded during the 48-hour study period . Postoperative follow-up was performed at 3 months . RESULTS : Demographic and surgical data were similar in both groups . Mean morphine consumption was significantly lower in the R-group than in the P-group during the first 48 postoperative hours : 45.4 ± 9.5 vs 69.7 ± 9.6 ( P < 0.0001 ) . There was a mean reduction of 14.4 mg for the first 24 postoperative hours ( 95 % confidence interval [ CI ] 12.6 to 16.1 ) and 20.8 mg for the next 24 hours ( 95 % CI 19.1 to 22.4 ) . Pain scores at rest and with motion were lower in the R-group ( P < 0.0001 ) . Mean patient satisfaction increased 22.7 % from baseline ( CI 95 % 15.9 to 29.6 ) in the R-group . Total and unbound ropivacaine plasma concentrations were below toxic levels in the R-group . The free ropivacaine concentration was 0.14 and 0.11 & mgr;gmol/L at T24 and T48 , respectively , in the R-group . At 3 months postoperatively , hip pain and analgesic consumption were similar , but a significant reduction in wound discomfort to touch ( 31.2 ; 95 % CI 27.7 to 34.7 ) and pressure ( 24 ; 95 % CI 20.1 to 27.9 ) was observed in the R-group ( P < 0.0001 ) . CONCLUSIONS : Continuous epicapsular wound infusion with ropivacaine 0.3 % after minimally invasive hip replacement is an efficient technique for reducing morphine consumption and improving the quality of postoperative analgesia . The beneficial effects of this technique are still present 3 months after surgery This study compares the efficacy of pain control using continuous femoral nerve block ( FNB ) and multimodal periarticular soft tissue injection . This is a r and omized , crossover , clinical trial . Sixteen patients having bilateral osteoarthritis of the knee scheduled for staged total knee arthroplasty were r and omized to receive either FNB ( 0.2 % ropivacaine ) , via indwelling catheter for 72 hours , or multimodal periarticular soft tissue injection in the first stage . In the second stage , they received the opposite treatment . The primary outcome measure was morphine consumption by patient-controlled analgesia in the first 72 hours postoperatively . Cumulative morphine consumption as well as rest pain and motion pain in the first 72 hours was comparable between the 2 groups . The functional outcomes did not differ significantly . We conclude that multimodal periarticular soft tissue injection provides comparable analgesia to continuous FNB after total knee arthroplasty In a r and omised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement ( TKR ) than patient-controlled epidural analgesia ( PCEA ) plus femoral nerve block . A total of 45 patients with a mean age of 65 years ( 49 to 81 ) received a local infiltration with a peri-articular injection of bupivacaine , morphine and methylprednisolone , as well as adjuvant analgesics . In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years ( 50 to 84 ) , analgesia included a bupivacaine nerve block , bupivacaine/hydromorphone PCEA , and adjuvant analgesics . The mean time until ready for discharge was 3.2 days ( 1 to 14 ) in the local infiltration group and 3.2 days ( 1.8 to 7.0 ) in the PCEA+femoral nerve blockade group . The mean pain scores for patients receiving local infiltration were higher when walking ( p = 0.0084 ) , but there were no statistically significant differences at rest . The mean opioid consumption was higher in those receiving local infiltration . The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery . Most secondary outcomes were similar , but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement . If PCEA+femoral nerve blockade is not readily available , local infiltration provides similar length of stay and similar pain scores at rest following TKR BACKGROUND Measures for pain management after total hip arthroplasty ( THA ) are important for early improvement in the quality of life after operation and early postoperative rehabilitation . We investigated the analgesic effect of locally injected drugs around the total hip prosthesis . METHODS 54 patients undergoing THA were r and omized either to receive a periarticular intraoperative injection of a 30-ml mixture containing morphine hydrochloride 10 mg , 0.5 % bupivacaine 20 ml , epinephrine 0.3 mg , and saline 8.7 ml or to receive no injection . The perioperative analgesic regimen was st and ardized . The evaluation items included assessment of pain using a 100-point visual analog scale ( VAS ) after the patients awoke on the day of the operation and on postoperative day 1 , the dose of diclofenac sodium suppository , the number of days for acquiring assisted ambulation with a walking cane , and side effects . RESULTS The VAS score on the day of the operation was significantly low in the injection group . No cardiac or central nervous system toxicity was observed . CONCLUSIONS Intraoperative periarticular injection with multimodal drugs can significantly reduce pain on the day of the operation , with no apparent risks , following THA BACKGROUND We report a prospect i ve blinded r and omised trial of local infiltration versus femoral nerve block in patients undergoing primary total knee replacement ( TKR ) , in accordance with the CONSORT statement 2010 . METHODS Fifty patients in a teaching hospital were consented for the study . The study arms were intraoperative local anaesthesia ( 150ml 0.2 % ropivacaine/1ml 1:1000 adrenaline/30 mg ketolorac ) and femoral nerve block ( 30ml 0.2 % ropivacaine ) with a primary outcome of pain score at 4h post operatively . Secondary outcomes were pain at 2h , pain scores before and after physiotherapy on day one , total opiate administered , time to physiotherapy goals and length of stay . R and omisation was by sealed envelope . The assessor was blinded and the patients partially blinded to the intervention . RESULTS Ten patients were excluded , eight before r and omisation . The trial is complete . Forty patients were analysed for the primary outcome measure . The local infiltration group had significantly lower pain scores at 4h post-operatively ; mean [ SD ] score 2.1 [ 2.6 ] versus 6.8 [ 3.2 ] , p<0.00001 and on post-operative day one prior to physiotherapy ; mean score 2.4 [ 2.3 ] versus 4.4 [ 2.3 ] , p<0.05 . Total opiate use was also significantly lower in the local infiltration group ; mean total 115 [50.3]mg versus 176.5 [103.5]mg , p<0.01 . There was no difference in any other outcome . There were no harms as a result of either intervention . CONCLUSION Intraoperative local infiltration gives superior pain relief compared to single shot femoral nerve block over the first 24h following primary TKR and minimises post-operative opiate use Background We have developed a multimodal technique for the control of pain following knee and hip surgery , called " local infiltration analgesia " ( LIA ) . It is based on systematic infiltration of a mixture of ropiva-caine , ketorolac , and adrenaline into the tissues around the surgical field to achieve satisfactory pain control with little physiological disturbance . The technique allows virtually immediate mobilization and earlier discharge from hospital . Patients and methods In this open , nonr and omized case series , we used LIA to manage postoperative pain in all 325 patients presenting to our service from Jan 1 , 2005 to Dec 31,2006 for elective hip resurfacing ( HRA ) , primary total hip replacement ( THR ) , or primary total knee replacement arthroplasty ( TKR ) . We recorded pain scores , mobilization times , and morphine usage for the entire group . Results Pain control was generally satisfactory ( numerical rating scale pain score range 0–3 ) . No morphine was required for postoperative pain control in two-thirds of the patients . Most patients were able to walk with assistance between 5 and 6 h after surgery and independent mobility was achieved 13–22 h after surgery . Orthostatic hypotension , nausea , and vomiting were occasionally associated with st and ing for the first time , but other side effects were unremarkable . 230 ( 71 % ) of the 325 patients were discharged directly home after a single overnight stay in hospital . Interpretation Local infiltration analgesia is simple , practical , safe , and effective for pain management after knee and hip surgery BACKGROUND Although numerous methods of postoperative analgesia have been investigated in an attempt to improve pain control after total knee arthroplasty , parenteral narcotics still play a major role in postoperative pain management . Local anesthetics have the advantage of blocking pain conduction at its origin and minimizing the systemic side effects associated with postoperative narcotic use . This study was performed to evaluate the benefits and safety of a multimodal analgesia protocol that included periarticular injection of large doses of local anesthetics in patients undergoing total knee arthroplasty . METHODS We compared morphine consumption during the first twenty-four hours after unilateral total knee arthroplasty in forty-two patients who had been r and omized to receive either ( 1 ) a perioperative infiltration mixture , consisting principally of local anesthetic , and self-administered morphine or ( 2 ) self-administered morphine only . Narcotics consumption , pain control , medication-related side effects , plasma levels of the local anesthetic ( ropivacaine ) , and postoperative rehabilitation were monitored . RESULTS Although there was high satisfaction and good pain control in both groups , morphine consumption was significantly lower in the local analgesia group than it was in the control group ( 28.8 + /- 17.4 mg compared with 50.3 + /- 25.4 mg twenty-four hours after surgery , and 46.7 + /- 19.4 mg compared with 68.6 + /- 38.6 mg forty hours after surgery ) . Both groups achieved a similar amount of knee flexion on the fifth postoperative day . Over the five-day period after the procedure , the patients in the local analgesia group reported a total of 2.6 + /- 3.9 hours of nausea compared with 7.1 + /- 12.2 hours in the control group . No complications related to the infiltration of the local anesthetic were observed , and all plasma concentrations of the local anesthetic were below the toxic range . CONCLUSIONS This multimodal perioperative analgesia protocol that included infiltration of a local anesthetic offered improved pain control and minimal side effects to patients undergoing total knee arthroplasty . Our study also confirmed the safety of the protocol A total of 100 osteoarthritis patients undergoing unilateral total knee arthroplasty were r and omly assigned to receive either a multimodal analgesia protocol , comprising oral celecoxib and tramadol before and after surgery and intra-articular injection of large doses of morphine , ropivacaine , adrenaline and betamethasone during surgery ( trial group ) , or oral and intra-articular placebo ( control group ) . All patients received patient-controlled analgesia for 48 h after surgery . Morphine consumption up to 48 h after surgery was significantly lower in the trial than in the control group . Compared with the control group , the trial group had significantly lower visual analogue scale ( VAS ) scores for pain at rest from 6 h to 7 days after surgery and significantly lower VAS scores during activity from 24 h to 7 days after surgery . Active straight leg raise and active 90 ° knee flexion were achieved sooner and range of knee movement at postoperative days 1–15 were significantly greater in the trial group . Postoperative wound healing , infection , blood pressure , heart rate , rash , respiratory depression , urinary retention and deep vein thrombosis were similar in the two groups , but nausea and vomiting were significantly less frequent in the trial group Background Multimodal cocktail periarticular injection ( MCPI ) with a large volume of low concentration local anesthetics , adrenaline , and anti‐inflammatory agents such as non‐steroidal anti‐inflammatory drug or steroids have shown good pain control and improvement in range of motion after surgery . This study compares the efficacy of pain control after total knee arthroplasty , using multimodal cocktail periarticular injection with steroid or without steroid . Methods This is a prospect i ve , double‐blinded , r and omized and control study . Seventy‐two patients with osteoarthritis that met clinical criteria for total knee arthroplasty were recruited into the study , and were r and omized to receive either multimodal cocktail periarticular injection with steroid or without steroid . Pain was assessed by visual analogue scale ( VAS ) at preoperative and postoperative at rest , and during activity . The range of motion was recorded preoperatively and postoperatively . The amount of daily and cumulative morphine consumption were measured by patient‐controlled analgesia in the first 72 hours postoperatively . The duration of celecoxib usage was also recorded at the last follow‐up . Results There were no differences between the non‐steroid and steroid groups with regard to VAS at rest and during activity , or range of motion , at any postoperative observation time . The postoperative Knee Society Knee Score in the steroid group improved significantly as compared with that in non‐steroid group at the one‐month ( 84.1±13.1 and 65.9±12.1 ; P < 0.0045 ) , three‐month follow‐up ( 90.2±16.3 and 72.5±16.6 ; P < 0.0027 ) , but after postoperative six‐month the Knee Society Knee Score showed no significant difference between the groups . There was no significant difference in consumption of the morphine about daily or total consumption within 72 hours between the two groups . The duration of celecoxib usage in patients in the steroid group was significantly shorter than that in the non‐steroid group ( ( 7.2±0.7 ) compared with ( 10.5±1.9 ) weeks ; P=0.012 ) . Conclusion The patients who received the steroid injection had faster rehabilitation and less non‐steroidal anti‐inflammatory drugs consumption BACKGROUND : Local infiltration analgesia (LIA)—using a combination of local anesthetics , nonsteroidal anti-inflammatory drugs , and epinephrine , injected periarticularly during surgery — has become popular in postoperative pain management after total knee arthroplasty ( TKA ) . We compared intrathecal morphine with LIA after TKA . METHODS : In this double-blind study , 50 patients scheduled to undergo TKA under spinal anesthesia were r and omized into 2 groups : group M , 0.1 mg morphine was injected intrathecally together with the spinal anesthetic and in group L , LIA using ropivacaine , ketorolac , and epinephrine was infiltrated in the knee during the operation , and 2 bolus injections of the same mixture were given via an intraarticular catheter postoperatively . Postoperative pain , rescue analgesic requirements , mobilization , and home readiness were recorded . Patient-assessed health quality was recorded using the Oxford Knee Score and EQ-5D during 3 months follow-up . The primary endpoint was IV morphine consumption the first 48 postoperative hours . RESULTS : Mean morphine consumption was significantly lower in group L than in group M during the first 48 postoperative hours : 26 ± 15 vs 54 ± 29 mg , i.e. , a mean difference for each 24-hour period of 14.2 ( 95 % confidence interval [ CI ] 7.6 to 20.9 ) mg . Pain scores at rest and on movement were lower during the first 48 hours in group L than in group M ( P < 0.001 ) . Pain score was also lower when walking in group L than in group M at 24 hours and 48 hours postoperatively ( P < 0.001 ) . In group L , more patients were able to climb stairs at 24 hours : 50 % ( 11 of 22 ) versus 4 % ( 1 of 23 ) , i.e. , a difference of 46 % ( 95 % CI 23.5 to 68.5 ) and at 48 hours : 70 % ( 16 of 23 ) versus 22 % ( 5 of 23 ) , i.e. , a difference of 48 % ( 95 % CI 23 to 73 ) . Median ( range ) time to fulfillment of discharge criteria was shorter in group L than in group M , 51 ( 24–166 ) hours versus 72 ( 51–170 ) hours . The difference was 23 ( 95 % CI 18 to 42 ) hours ( P = 0.001 ) . Length of hospital stay was also shorter in group L than in group M : median ( range ) 3 ( 2–17 ) versus 4 ( 2–14 ) days ( P = 0.029 ) . Patient satisfaction was greater in group L than in group M ( P = 0.001 ) , but no differences were found in knee function , side effects , or in patient-related outcomes , Oxford Knee score , or EQ-5D . CONCLUSIONS : LIA technique provided better postoperative analgesia and earlier mobilization , result ing in shorter hospital stay , than did intrathecal morphine after TKA Postoperative pain control after total knee arthroplasty ( TKA ) is a well-known clinical problem . Efforts to treat it with the use of local anesthesia have been made , but the results have been contradictive . In the late 1990s , an infiltrated solution of ropivacaine/ketorolac/adrenaline was shown to be effective for this purpose , and this technique has since spread over the world . The purpose of this study was to compare the local infiltration anesthesia technique with epidural anesthesia , which has been the most widely used technique in Sweden . Eighty-five patients received either local infiltration anesthesia or epidural anesthesia for postoperative pain relief . Postoperative morphine consumption , range of motion , walking ability , patient satisfaction , hospital stay , and time in the recovery room were measured . The groups were followed equally . The patients in the local infiltration anesthesia group were mobilized 24 hours earlier . On postoperative day one , 22 of 33 patients in the local infiltration anesthesia group could get in and out of bed without assistance . Only 1 of 31 patients in the epidural anesthesia group could manage this . On postoperative day two , 28 of 33 patients in the local infiltration anesthesia group could walk without assistance , compared to 5 of 31 in the epidural anesthesia group . Seventy-six percent of the local infiltration anesthesia patients were " very satisfied " with their postoperative pain control method , compared to 40 % of the epidural anesthesia patients .The local infiltration anesthesia technique is better for postoperative pain relief in TKA than epidural anesthesia . It offers equal pain relief , faster mobilization , and more satisfied patients . No negative side effects were seen during the study We investigated the hypothesis that a posterior capsular injection of ropivacaine would improve pain and accelerate functional recovery after total knee arthroplasty in a r and omized , double-blind , placebo-controlled study design . Sixty-six patients received a st and ardized multimodal anesthesia protocol that included a femoral nerve block . Twenty milliliters of either saline ( control ) or ropivacaine ( study group ) was injected into the posterior capsule . Pain and function outcomes were recorded prospect ively at 4 , 8 , 12 , and 24 hours postinjection . Significantly more patients in the study group were able to perform a straight-leg raise at 8 and 12 hours . In addition , significantly more patients in the control group had a numeric pain score higher than 7/10 ( severe pain ) at the 12-hour evaluation . Other parameters of pain or functional recovery were not significantly different between the 2 groups . Posterior capsular injection did not improve the pain or accelerate the functional recovery after 12 hours in patients also receiving a femoral nerve block for pain control after total knee arthroplasty In a r and omized , double-blind , placebo , parallel and controlled study , 80 patients with osteoarthritis who underwent unilateral TKA were r and omly assigned to two groups : Trial Group , where patients received intra-articular intraoperative injection containing morphine , bupivacaine and betamethasone , and Control Group , where patients received normal saline as control . All patients received patient-controlled analgesia ( PCA ) for 48 h postoperatively . We found that intra-articular cocktail analgesic injection significantly reduced the morphine consumption during the 0 - 36 h postoperative period and the total morphine consumption . VAS at rest in Trial Group at postoperative 6 , 10 , 24 and 36 h was significantly lower than that in Control Group , and VAS during activity in Trial Group at postoperative 24 h and 36 h was significantly lower than that in Control Group . The time of ability to perform an active straight leg raise and to actively reach 90 degrees knee flexion , as well as ROM of the knee at the 15th postoperative day , was better in Trial Group than those in Control Group . There were no significant differences in postoperative wound healing , infection , blood pressure , heart rate , rash , respiratory depression , urine retention and DVT between the two groups . The occurrence of nausea and vomiting in Trial Group was lower than that of Control Group . This study revealed that intra-articular cocktail analgesic injection reduced the need for morphine and offered a better pain control , without apparent risks following TKA |
10,385 | 25,758,180 | Authors ' conclusions Among the evaluated tests for S. haematobium infection , microhaematuria correctly detected the largest proportions of infections and non‐infections identified by microscopy .
The CCA POC test for S. mansoni detects a very large proportion of infections identified by microscopy , but it misclassifies a large proportion of microscopy negatives as positives in endemic areas with a moderate to high prevalence of infection , possibly because the test is potentially more sensitive than microscopy . | Abstract Background Point‐of‐care ( POC ) tests for diagnosing schistosomiasis include tests based on circulating antigen detection and urine reagent strip tests .
If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use .
Objectives To summarise the diagnostic accuracy of : a ) urine reagent strip tests in detecting active Schistosoma haematobium infection , with microscopy as the reference st and ard ; and b ) circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium or both , with microscopy as the reference st and ard . | This prospect i ve study was design ed to look for and describe urologic and nephrologic consequences of urinary bilharziosis due to schistosoma haematobium in a hyperendemic hotbed in the middle west of Madagascar . Methodology included clinical examination , kidney and bladder ultrasonography , urine dipsticks and creatininemia . Amongst a population of 574 persons aged 5 years ore more , 436 ( 76 % ) had bilharziosis ova in the urine ( filtration method ) . From the clinical point of view , 257 patients ( 58.9 % ) had microscopic hematuria , 178 ( 40.8 % ) had presently an hematuria ; 111 patients ( 25.5 % ) suffered from dysuria ; 18 patients ( 4.1 % ) had limb oedema when 3 patients had present oedema ( 0.7 % ) . Among 436 checked people , 267 ( 61.2 % ) had an ultrasonography abnormality . In 252 , it was bladder wall abnormalities ( 57.8 % ) . They were wall irregularities in 182 cases ( 41.7 % ) ; vesico-ureteral reflux in 22 cases ( 5.3 % ) ; ureteral dilatations in 22 cases ( 5.3 % ) and pyelocalyceal dilatations in 61 cases ( 13.9 % ) . Prevalence of proteinuria 75.2 % ( 316 amongst 420 checked people ) of whom 5.7 % ( 24 cases ) had 5 g/l or more . Hematuria was found in 352 patients ( 83.8 % ) of whom 238 ( 56.7 % ) had more than 250 erythrocytes per microliter . Prevalence of leucocyturia was 56.7 % ( 238 cases ) . Creatininemia was measured in 140 people with positive filtration ; it was normal in all except two patients . This study highlights the parallel evolution between parasitic infection and uronephrological manifestations of the disease UNLABELLED An earlier reported laboratory assay , performed in The Netherl and s , to diagnose Schistosoma infections by detection of the parasite antigen CAA in serum was converted to a more user-friendly format with dry reagents . The improved assay requires less equipment and allows storage and worldwide shipping at ambient temperature . Evaluation of the new assay format was carried out by local staff at Ampath Laboratories , South Africa . The lateral flow ( LF ) based assay utilized fluorescent ultrasensitive up-converting phosphor ( UCP ) reporter particles , to be read by a portable reader ( UPlink ) that was also provided to the laboratory . Over a period of 18 months , about 2000 clinical sample s were analyzed prospect ively in parallel with a routinely carried out CAA-ELISA . LF test results and ELISA data correlated very well at CAA concentrations above 300 pg/mL serum . At lower concentrations the UCP-LF test indicates a better performance than the ELISA . The UCP-LF strips can be stored as a permanent record as the UCP label does not fade . At the end of the 18 months testing period , LF strips were shipped back to The Netherl and s where scan results obtained in South Africa were vali date d with different UCP scanning equipment including a novel , custom developed , small lightweight UCP strip reader ( UCP-Quant ) , well suited for testing in low re source setting s. CONCLUSION The dry format UCP-LF assay was shown to provide a robust and easy to use format for rapid testing of CAA antigen in serum . It performed at least as good as the ELISA with respect to sensitivity and specificity , and was found to be superior with respect to speed and simplicity of use . Worldwide shipping at ambient temperature of the assay reagents , and the availability of small scanners to analyze the CAA UCP-LF strip , are two major steps towards point-of-care ( POC ) applications in remote and re source poor environments to accurately identify low ( 30 pg CAA/mL serum ; equivalent to about 10 worm pairs ) to heavy Schistosoma infections Quantitative parasitological assessment and quantitative analysis of proteinuria , hematuria , and leukocyturia were carried out in 182 Sudanese schoolboys with mixed urinary and intestinal schistosomiasis . Pathological proteinuria was found in 73 % of patients ( median = 380 , 95 % confidence limits = 200 to 500 mg/liter ) . The median protein/creatinine ratio was 0.54 . SDS polyacrylamide gel electrophoresis showed an excretion of albumin , transferrin , and IgG consistent with a postrenal pattern of proteinuria . Pathological erythrocyturia occurred in 84 % of patients ( median = 255 , 95 % CL = 95 to 629 cells/microliter ) and leukocyturia in 77 % of patients ( median = 148 , 95 % CL = 93 to 246 cells/microliter ) . Phase contrast microscopy revealed intact erythrocytes , suggestive of postrenal hemorrhage . Proteinuria , erythrocyturia , and leukocyturia correlated significantly with the ova excretion in the urine , but not with egg excretion in the stool . Oxamniquine reduced ova excretion in the stool but did not influence pathological urine findings . In patients treated effectively with Praziquantel or Metrifonate , pathological PU , EU , and LU decreased markedly 1 month post treatment . PU in severely proteinuric patients reached physiological values 5 months post therapy . We suggest that the proteinuria , erythrocyturia , and leukocyturia in mixed schistosomiasis were of postrenal origin Health question naires and parasitologic examinations of urine and stool were performed upon a stratified r and om sample of 7,710 individuals from 1,109 households in 21 rural communities in Fayoum Governorate , Egypt in 1992 to investigate the prevalence of , risk factors for , and changing pattern of , infection with Schistosoma sp. in the governorate . A subset , every fifth household , or 1,038 subjects , had physical and ultrasound examinations to investigate prevalence of , and risk factors for , morbidity . The prevalence of S. haematobium ranged from 0 % to 27.1 % and averaged 13.7 % . The geometric mean egg count ( GMEC ) was 10.0 eggs/10 ml of urine . Age-stratified prevalence and intensity of infection were 18 - 25 % and 10 - 15 eggs/10 ml of urine in those 5 - 25 years of age . Schistosoma mansoni were detected in inhabitants of 13 communities , but 78.5 % of the infections were focally present in a group of 4 satellite hamlets around a single village . The overall prevalence of S. mansoni in the governorate was 4.3 % and the GMEC was 44.0 ova/g of stool . Risk factors for infection with either species were male gender , an age < 20 years , living in smaller communities , and exposures to canal water by males . Histories of burning micturation , blood in the urine , or prior schistosomiasis and reagent strip-detected hematuria and proteinuria were risks for S. haematobium , but not for S. mansoni . Both urinary tract and higher grade s of hepatic morbidity were rare . Obstructive uropathy was present in 6.3 % of the subjects and was more common in males and older people . Ultrasonography-detected bladder lesions were present in 5.2 % and correlated with S. haematobium only in younger subjects and in those with hematuria and proteinuria . The prevalences of hepatomegaly , splenomegaly , and periportal fibrosis ( PPF ) were associated with each other and increased with age and in males . Ultrasonography-detected hepatomegaly and splenomegaly were weakly associated with S. mansoni infections only in children . The prevalence of PPF was greater in the 4 communities with > 25 % S. mansoni infection rates in comparison with the 17 other villages and ezbas . Transmission of S. mansoni is focally well established in Fayoum , which also has the highest prevalence of S. haematobium in the governorates surveyed by the Epidemiology 1 , 2 , 3 Project . However , both urinary tract and hepatic morbidity are relatively rare in the governorate . This probably results from the long-st and ing schistosomiasis control program in Fayoum , which suppressed intensity more than prevalence of infection , leading to less community morbidity Using Hansel 's stain , eosinophiluria greater than 5 % of total urinary white blood cells was found in 59 % of a r and omly selected population sample in an area endemic for schistosomiasis hematobium . The prevalence and mean level of eosinophiluria were significantly higher in infected subjects than in noninfected subjects ( P less than 0.05 ) . The sensitivity ( 80 % ) , specificity ( 86 % ) , and positive predictive value ( 82 % ) of eosinophiluria as a diagnostic index for schistosomiasis hematobium were significantly higher ( Youdin index 0.66 ; P less than 0.05 ) than those of proteinuria , hematuria , and leukocyturia taken singly or in combination . However , unlike the latter three measurements , this method involves microscopy . There is a great need for a chemical method for measuring eosinophiluria Schistosomiasis is a public health problem in Nigeria . Although there is a national programme for its control , there is the need for reliable and simple means of rapidly diagnosing communities to provide a detailed map on the distribution of the disease in the country , in order to prioritize control activities , as well as to monitor the effectiveness of control operations . A rapid assessment technique using school question naires was tested in Borgu Local Government Area ( LGA ) , Niger State , north-western Nigeria . Following a series of focus group discussion s , the question naires were adapted before they were administered through the school system to 60 primary schools in Borgu LGA . Correctly completed question naires were returned from 58 schools ( 97 % ) within 4 weeks . Question naires were vali date d by reagent stick tests performed by trained teachers . Their results proved to be reliable compared to those obtained by our research team in 20 r and omly selected schools . Overall prevalences of microhaematuria at 1 + and 2 + levels were 45.7 % and 27 . 1 % , respectively . Highly significant correlations were obtained between school prevalence of microhaematuria and reported schistosomiasis , as well as reported blood in urine . The diagnostic performance of the question naires at the 2 + level of microhaematuria was very good . The design of our study also allowed data analysis on an individual level , and multivariate analysis revealed highly significant odds ratios for reported schistosomiasis and reported blood in urine to detect an individual with urinary schistosomiasis . Our results are in good agreement with reports from other African countries , and question naires can be recommended for rapid identification of communities at highest risk of urinary schistosomiasis in Nigeria , so that scarce re sources of the national control programme can be used most effectively To determine the effect of targeted field administration of oral chemotherapeutic agents on the prevalence , intensity , and morbidity of Schistosoma haematobium infections , we initiated a long-term school-based program in the Msambweni area of Kwale District , Coast Province , Kenya . Prior to treatment , 69 % of the children examined ( ages 4 - 21 , n = 2,628 ) were infected ; 34 % had moderate or heavy infections ( greater than 100 eggs/10 ml urine ) . Infected individuals were r and omized to receive , during one year , either metrifonate ( 10 mg/kg x 3 doses ) or praziquantel , ( 40 mg/kg x 1 dose ) . At the end of the first year , prevalence of infection fell to 19 % ; only 2 % of the pupils remained in the moderately and heavily infected groups . Corresponding decreases in the prevalence of hematuria ( 54 % in 1984 vs. 16 % in 1985 ) and proteinuria ( 56 % in 1984 vs. 26 % in 1985 ) were noted . These were associated with significant declines in bladder thickening and irregularities noted during ultrasound examinations , but not with decreases in hydronephrosis . There was no significant difference in the post-treatment prevalence or intensity of infection after treatment with metrifonate as compared with praziquantel . These results demonstrate that field-applied chemotherapy with either agent offers a practical strategy for the control of S. haematobium infection and its associated morbidity We evaluated the ability of circulating anodic antigen ( CAA ) to identify infection with Schistosoma mansoni in a prospect i ve cohort study of 257 Egyptian men , 147 with infection diagnosed by repeated Kato thick smears , and 110 without detectable infection . The CAA levels were obtained and the stool examinations were performed two weeks and one , two , four , and six months after praziquantel therapy for infected men . A CAA enzyme-linked immunosorbent assay was repeated twice on subjects who were otherwise negative for schistosomiasis . Circulating anodic antigen was detected in 117 cases , with an overall test sensitivity before treatment of 0.8 . Sensitivity was related to the intensity of infection , ranging from 1.00 with > 400 eggs per gram ( epg ) of feces to 0.60 for those with < 100 epg . After praziquantel therapy , the level of the antigen was significantly reduced . Specificity was excellent before treatment ( 1.00 , 95 % confidence interval = 0.97 - 1.0 ) , but it decreased to 0.98 four months after treatment . Likelihood ratios were significant for all titers > or = 4 . We conclude that CAA has moderate sensitivity and excellent specificity when used to identify infection with schistosomiasis , as well as to monitor the results of therapy after at least one month after treatment Diagnosis of schistosomiasis at the point-of-care ( POC ) is a growing topic in neglected tropical disease research . There is a need for diagnostic tests which are affordable , sensitive , specific , user-friendly , rapid , equipment-free and delivered to those who need it , and POC is an important tool for disease mapping and guiding mass deworming . The aim of present study was to evaluate the relative diagnostic performance of two urine-circulating cathodic antigen ( CCA ) cassette assays , one commercially available and the other in experimental production , against results obtained using the st and ard Kato-Katz faecal smear method ( six thick smears from three consecutive days ) , as a ' gold-st and ard ' , for Schistosoma mansoni infection in different transmission setting s in Ug and a. Our study was conducted among 500 school children r and omly selected across 5 schools within Bugiri district , adjacent to Lake Victoria in Ug and a. Considering results from the 469 pupils who provided three stool sample s for the six Kato-Katz smears , 293 ( 76 % ) children had no infection , 109 ( 23 % ) were in the light intensity category , while 42 ( 9 % ) and 25 ( 5 % ) were in the moderate and heavy intensity categories respectively . Following performance analysis of CCA tests in terms of sensitivity , specificity , negative and positive predictive values , overall performance of the commercially available CCA test was more informative than single Kato-Katz faecal smear microscopy , the current operational field st and ard for disease mapping . The current CCA assay is therefore a satisfactory method for surveillance of S. mansoni in an area where disease endemicity is declining due to control interventions . With the recent resolution on schistosomiasis elimination by the 65th World Health Assembly , the urine POC CCA test is an attractive tool to augment and perhaps replace the Kato-Katz sampling within ongoing control programmes To gain better underst and ing of the natural history of Schistosoma haematobium associated disease , age- and intensity-related urinary tract morbidity were assessed in a cross-sectional study of Kilole ( population 719 ) in Coast Province , Kenya . Overall prevalence of infection was 65 % ( 39 % light , 16 % moderate , 9 % heavy ) . Infection prevalence and mean intensity of infection were highest in the 5 - 14-year-old bracket for both sexes . Although significant intensity-associated increases in hematuria prevalence were noted for both children and adults in all infection categories , hematuria was more common in those less than 15 years of age . Children had a significant increase in the prevalence of dysuria at higher levels of infection , whereas adults did not . Radiographic study of a 1:9 r and om sample , stratified for age , revealed a greater prevalence of urinary tract granulomas in those less than 15 years . Subjects greater than 15 years of age had a greater frequency of hydronephrosis . Hydronephrosis , hydroureter , and bladder calcification were not associated with higher infection intensity . Among individuals with bladder calcification , a potential marker of cumulative inflammation , 87 % had hydronephrosis or hydroureter , compared to a 40 % prevalence among individuals without bladder calcification . These findings suggest that certain structural forms of urinary tract disease , such as hydronephrosis , progress during the course of untreated schistosomiasis haematobia despite age-related reductions in egg burden , whereas other forms of morbidity , such as hematuria , remain sensitive to the level of urinary egg excretion at the time of diagnosis The kinetics of serum levels of circulating anodic antigen ( CAA ) of Schistosoma mansoni were studied in patients with intestinal schistosomiasis before and after treatment with praziquantel . Day to day fluctuation in faecal egg excretion was compared with fluctuation in antigen level in 20 patients by serum and stool examination on 3 consecutive days before treatment . Antigen levels - calculated either as absorbance value of undiluted serum or as titre - showed less fluctuation than the number of eggs per gram of faeces determined by stool examinations based on single or duplicate 25 mg Kato smears . Compared with a placebo control group of 11 individuals , there was a significant reduction in CAA level in serum of 10 patients treated with praziquantel ( 40 mg/kg ) , 10 weeks after treatment . A similar decrease in serum CAA level was observed in a group of 46 patients treated with praziquantel , 6 weeks after treatment . In both groups , patients who remained seropositive after treatment still excreted eggs in their faeces . The kinetics of the antigen decrease were studied in more detail in 20 patients in hospital . Within 10 d after treatment with a double dose of 40 mg praziquantel per kg body weight , the antigen level fell to less than 10 % of the original serum level , with a CAA half-life of approximately 2 OBJECTIVE To evaluate urine albumin-to-creatinine ratio ( UACR ) reagent strips for detection of urinary tract pathology ( UTP ) associated with urinary schistosomiasis in schoolchildren from Zanzibar . PATIENTS AND METHODS Sixty-six schoolchildren were examined for urinary schistosomiasis and UTP using urine reagent strips ( Hemastix , urine microscopy and portable ultrasonography . The UACR was estimated using Microalbustix ; univariate and logistic regression methods were used to test for statistical associations . RESULTS Prevalence of egg-patent schistosomiasis was 65.2 % while 77.3 % had micro-haematuria and 66.1 % had a least one ultrasound-identified UTP . Abnormal UACR ( > or = 3.4 mg/mmol ) was frequent ( 88.4 % ) but an unsatisfactory identifier of UTP , albeit highly sensitive : sensitivity ( SS ) = 100.0 % , specificity ( SP ) = 23.8 % , positive predictive value ( PPV ) = 71.9 % , negative predictive value ( NPV ) = 100.0 % . When only severely abnormal UACR was considered ( > or = 33.9 mg/mmol ) , SS decreased while SP improved : SS = 58.5 % , SP = 61.9 % , PPV = 75.0 % , NPV = 43.3 % . CONCLUSION Abnormal and severely abnormal UACRs were strongly associated with egg-patent urinary schistosomiasis and UTP , although via different mechanisms : respectively , from venous blood released directly into the urine from bladder wall perforations , and from leaching sera released from chronic egg-induced lesions throughout the urinary tract . From a control perspective , Microalbustix reagent strips are therefore best applied in pre-screening protocol s allowing selection , or rather confident exclusion , of schoolchildren with urinary schistosomiasis for more detailed investigations A cohort of 148 Cameroonian children infected with Schistosoma haematobium was followed before praziquantel therapy and 1 , 2 , 3 , 5 , and 12 months thereafter . Egg output , the reagent strip index ( RSI , a pathological marker ) , and circulating anodic antigen ( CAA ) and circulating cathodic antigen ( CCA ) in serum and urine were quantified . At enrollment , the median level of egg output was 365/10 mL of urine ; 97 % of children had a positive RSI ; CAA was detected in serum from 76 % of children and in urine from 64 % ; and CCA was detected in serum from 55 % of children and in urine from 87 % . Two months after chemotherapy , egg output and RSI had decreased significantly ; reinfection later developed in parallel with increases in the serum and urine concentrations of CAA and the urine concentrations of CCA . The measurement of CAA and CCA is useful for diagnosis , evaluation of disease severity , and follow-up of chemotherapy in individuals infected with S. haematobium Risk factors , prevalence , and intensity of infection with Schistosoma sp. and prevalence and magnitude of morbidity caused by schistosomiasis was assessed in a stratified r and om sample of 16,433 subjects from 2,409 households in 33 rural communities in Minya Governorate , Egypt . The prevalence of S. haematobium ranged from 1.9 % to 32.7 % among the communities and averaged 8.9 % . The average intensity of infection was a geometric mean egg count ( GMEC ) of 8.5 per 10 ml of urine and ranged from 1.6 to 30.9 . Prevalence was maximum ( 18 - 20 % ) in those 10 - 20 years of age and higher in males than in females . Intensity of infection followed the same pattern . Infection with S. mansoni was present almost exclusively in a single village , confirming spread of this species up the Nile River and its focality in Minya . Risk factors for S. haematobium infection were an age from 11 to 20 ; male gender ; males bathing in , women washing clothing or utensils in , and children swimming or playing in canals ; and a history of , or treatment for , schistosomiasis . Recent history of burning micturition was associated with infection in children but not in adults , while a history of blood in urine correlated with S. haematobium infection in both age groups . Reagent strip-detected hematuria and proteinuria were highly associated , particularly in children , with S. haematobium infection . The presence of hepatomegaly or splenomegaly on physical examination was not associated with S. haematobium ova in the urine . Hepatomegaly , as measured by ultrasonography in the midclavicular line or the midsternal line , or ultrasonography-detected splenomegaly were not present more frequently in infected subjects than in uninfected subjects . Schistosoma ova were not detected more frequently in urine of subjects with ultrasonography-detected periportal fibrosis than in the urine from subjects without this finding . Ultrasonography-detected urinary bladder wall lesions were detected in only 6 ( 0.3 % ) subjects and obstructive uropathy was observed in 54 ( 2.7 % ) subjects . The absence of an association between prevalence of urinary tract morbidity and S. haematobium infections was surprising . Two possible explanations are 1 ) that repeated chemotherapy has reduced the prevalence of urinary tract morbidity and 2 ) that morbidity was not being detected by the ultrasonographic operators The operational and diagnostic performance of a two-step method for the cost-effective screening of urinary schistosomiasis was investigated in the Kilosa District of east- central Tanzania . In the first step a simple question naire was administered to 15,073 primary schoolchildren by their class teachers over a 4-week period . The answers to the question naires had a high negative predictive value for schistosomiasis , and this permitted the safe exclusion of schools where the risk of the disease was low . In the second step , the head-teachers of the 49 high-risk schools and of 26 low-risk schools were instructed on the use of reagent sticks to detect haematuria . Each head-teacher then performed this test on 80 children selected at r and om in their schools ( 5750 children were screened within 6 weeks ) . Crosschecks of the results in 18 schools confirmed the reliability of the head-teachers ' testing and their findings were therefore used to prepare an epidemiological map of the district and to arrange for treatment of positive children . This two-step approach relied entirely on the existing school system and permitted screening of a rural district of area 15,000 km2 ( population , 350,000 ) over a 4-month period at a cost of only US$ 3000 Several studies of schistosomiasis haematobia in Africa have revealed a correlation between intensity of infection as measured by urine egg counts and severity of disease as determined by intravenous pyelography . The present study consisted of a survey of 390 school children in the coastal area of Kenya involving a single egg count , and intravenous pyelograms in a stratified r and om sample of 69 children ; the results showed a greater prevalence of urinary tract disease in those with higher intensities of infection . This survey was then followed by a more detailed study in which nine consecutive daily egg counts were done on 121 children ; 17 of these children , subdivided into three groups with different intensities in infection , were given intravenous pyelograms . The results were similar in the 11 children with minimal and moderate counts ( averaging , respectively , less than 1 egg and 167 eggs/10 ml urine daily ) , with approximately 30 % having bladder or renal abnormalities . In comparison , all of the six children with heavy counts ( averaging 1,288 eggs/10 ml urine daily ) had bladder lesions and five of them had renal lesions In this study , levels of circulating anodic antigen ( CAA ) in serum were investigated after differential treatment of 160 Sudanese patients with mixed Schistosoma haematobium and S. mansoni infections . The patients were r and omly divided into four groups , which were treated with metrifonate ( two doses of 10 mg/kg bodyweight ) , oxamniquine ( 60 mg/kg ) , praziquantel ( 40 mg/kg ) , or a multivitamin preparation , respectively . Serum , stool and urine sample s were taken prior to treatment as well as one month and five months after chemotherapy . Before chemotherapy CAA levels were similar in the four groups . Antigenemia remained unchanged in the control group . In patients treated with praziquantel or oxamniquine the concentration of CAA decreased to a similar extent . However , whereas in the praziquantel group absence of CAA was already observed one month after treatment , clearing of CAA from the circulation seemed to take longer in patients treated with oxamniquine . Treatment with metrifonate did not result in a reduction of the CAA titres An investigation of a population -based stratified r and om sample of 11,970 inhabitants of Minya Governorate in Egypt included examining urine specimens for Schistosoma haematobium ova using the filtration technique and for hematuria and proteinuria using reagent strips . Age- and gender-specific sensitivity , specificity , predictive values , and likelihood ratios of reagent strip-detected hematuria and proteinuria as indicators of S. haematobium infection were assessed . Results showed that in this population with a 9.0 % infection rate , sensitivity ( from 45.9 to 70.9 ) and specificity ( from 65.9 to 86.3 ) were much lower than in previous reports . The most clinical ly valuable parameters , positive predictive value ( PPV ) , negative predictive value ( NPV ) and likelihood ratio ( LR ) , were highest with the presence of hematuria > or = + + + and proteinuria > or = + + , especially in males less than 20 years of age . Using the LR allowed effective altering of the pretest probability of infection among age and gender subgroups . The study concluded that reagent strip-detected hematuria and proteinuria , although valuable , are less reliable predictors of S. haematobium within communities than previously reported and their usefulness is improved with stratification by age and gender . In addition , predictive values and likelihood ratios provide practical information for predicting the presence or absence of infection within population subgroups Schistosomiasis is one of the major parasitic infections of man in the tropical and subtropical areas of the world . Diagnosis of the disease is usually based on microscopic detection of eggs in excreta which is both laborious and time consuming . In Nigeria , the Government 's emphasis on the control of the disease dictates the need for a simple , fast , reliable and affordable diagnostic test for the identification of infected communities and detection of infected persons . Three indirect diagnostic tests for urinary schistosomiasis : interview technique , visual examination for macrohaematuria and the use of a chemical reagent strip were employed in screening 1056 individuals of the Kainji Lake area of Nigeria for urinary schistosomiasis , using haematuria as the disease indicator . The sensitivity of the three tests were determined using the filtration ( egg counting ) technique as the reference test . The sensitivity of the reagent strip test was 69.0 % and 44 and 38 % for the interview technique and visual examination respectively . The reagent strip test was particularly useful for screening children ( 5 - 19 years old ) . The implication of these findings are discussed |
10,386 | 23,110,958 | Years of basic science research , clinical trials , and systematic review s and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients , improving the allergic individuals ’ quality of life , reducing the long-term costs and burden of allergies , and changing the course of the disease .
Allergen specific immunotherapy not only effectively alleviates allergy symptoms , but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases . | Allergy today is a public health concern of p and emic proportions , affecting more than 150 million people in Europe alone .
In view of epidemiological trends , the European Academy of Allergy and Clinical Immunology ( EAACI ) predicts that within the next few decades , more than half of the European population may at some point in their lives experience some type of allergy .
Not only do allergic patients suffer from a debilitating disease , with the potential for major impact on their quality of life , career progression , personal development and lifestyle choices , but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance .
Given that allergy triggers , including urbanization , industrialization , pollution and climate change , are not expected to change in the foreseeable future , it is imperative that steps are taken to develop , strengthen and optimize preventive and treatment strategies .
Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease . | BACKGROUND We wondered whether short-term coseasonal sublingual immunotherapy ( SLIT ) can reduce the development of asthma in children with hay fever in an open r and omized study . OBJECTIVE We sought to determine whether SLIT is as effective as subcutaneous immunotherapy in reducing hay fever symptoms and the development of asthma in children with hay fever . METHODS One hundred thirteen children aged 5 to 14 years ( mean age , 7.7 years ) with hay fever limited to grass pollen and no other clinical ly important allergies were r and omized in an open study involving 6 Italian pediatric allergy centers to receive specific SLIT for 3 years or st and ard symptomatic therapy . All of the subjects had hay fever symptoms , but at the time of study entry , none reported seasonal asthma with more than 3 episodes per season . Symptomatic treatment was limited to cetirizine , loratadine , nasal budesonide , and salbutamol on dem and . The hay fever and asthma symptoms were quantified clinical ly . RESULTS The actively treated children used less medication in the second and third years of therapy , and their symptom scores tended to be lower . From the second year of immunotherapy , subjective evaluation of overall allergy symptoms was favorable in the actively treated children . Development of asthma after 3 years was 3.8 times more frequent ( 95 % confidence limits , 1.5 - 10.0 ) in the control subjects . CONCLUSIONS Three years of coseasonal SLIT improves seasonal allergic rhinitis symptoms and reduces the development of seasonal asthma in children with hay fever BACKGROUND Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis , although it is question able whether there is long-term benefit after the discontinuation of treatment . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective . During the three years of this trial , primary outcome measures were scores for seasonal symptoms and the use of rescue medication . Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge . Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells ( TH2 cells ) ( as evidence d by the presence of interleukin-4 messenger RNA ) . A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease . RESULTS Scores for seasonal symptoms and the use of rescue antiallergic medication , which included short courses of prednisolone , remained low after the discontinuation of immunotherapy , and there was no significant difference between patients who continued immunotherapy and those who discontinued it . Symptom scores in both treatment groups ( median areas under the curve in 1995 , 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy ; P=0.60 ) were markedly lower than those in the group that had not received immunotherapy ( median value in 1995 , 2863 ) . Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation , there was a sustained reduction in the late skin response and associated CD3 + T-cell infiltration and interleukin-4 messenger RNA expression . CONCLUSIONS Immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity BACKGROUND It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma . METHODS We r and omly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate ( at a dose of 88 mug twice daily ) or masked placebo for two years , followed by a one-year period without study medication . The primary outcome was the proportion of episode-free days during the observation year . RESULTS During the observation year , no significant differences were seen between the two groups in the proportion of episode-free days , the number of exacerbations , or lung function . During the treatment period , as compared with placebo use , use of the inhaled corticosteroid was associated with a greater proportion of episode-free days ( P=0.006 ) and a lower rate of exacerbations ( P<0.001 ) and of supplementary use of controller medication ( P<0.001 ) . In the inhaled-corticosteroid group , as compared with the placebo group , the mean increase in height was 1.1 cm less at 24 months ( P<0.001 ) , but by the end of the trial , the height increase was 0.7 cm less ( P=0.008 ) . During treatment , the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth , albeit temporarily and not progressively . CONCLUSIONS In preschool children at high risk for asthma , two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third , treatment-free year . These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued . ( Clinical Trials.gov number , NCT00272441 . ) Background : Allergic rhinitis was recently classified by the ARIA guidelines as persistent or intermittent . Levocetirizine was shown to improve symptoms and health‐related quality of life of patients with persistent allergic rhinitis in the XPERTTM study , a 6‐month r and omized double blind placebo‐controlled trial BACKGROUND Data for trends in prevalence of asthma , allergic rhinoconjunctivitis , and eczema over time are scarce . We repeated the International Study of Asthma and Allergies in Childhood ( ISAAC ) at least 5 years after Phase One , to examine changes in the prevalence of symptoms of these disorders . METHODS For the ISAAC Phase Three study , between 2002 and 2003 , we did a cross-sectional question naire survey of 193,404 children aged 6 - 7 years from 66 centres in 37 countries , and 304,679 children aged 13 - 14 years from 106 centres in 56 countries , chosen from a r and om sample of schools in a defined geographical area . FINDINGS Phase Three was completed a mean of 7 years after Phase One . Most centres showed a change in prevalence of 1 or more SE for at least one disorder , with increases being twice as common as decreases , and increases being more common in the 6 - 7 year age-group than in the 13 - 14 year age-group , and at most levels of mean prevalence . An exception was asthma symptoms in the older age-group , in which decreases were more common at high prevalence . For both age-groups , more centres showed increases in all three disorders more often than showing decreases , but most centres had mixed changes . INTERPRETATION The rise in prevalence of symptoms in many centres is concerning , but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring . The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders BACKGROUND The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials . OBJECTIVE To investigate sustained efficacy and disease modification in a 5-year double-blind , placebo-controlled trial , including 2 years of blinded follow-up after completion of a 3-year period of treatment , with the SQ-st and ardized grass allergy immunotherapy tablet , Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU,(∗ ) ALK , Denmark ) or placebo . METHODS A r and omized , double-blind , placebo-controlled , multinational , phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis , with or without asthma , inadequately controlled by symptomatic medications . Two hundred thirty-eight participants completed the trial . End points included rhinoconjunctivitis symptom and medication scores , combined scores , asthma symptom and medication scores , quality of life , days with severe symptoms , immunologic end points , and safety parameters . RESULTS The mean rhinoconjunctivitis daily symptom score was reduced by 25 % to 36 % ( P ≤ .004 ) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial . The rhinoconjunctivitis DMS was reduced by 20 % to 45 % ( P ≤ .022 for seasons 1 - 4 ; P = .114 for season 5 ) , and the weighted rhinoconjunctivitis combined score was reduced by 27 % to 41 % ( P ≤ .003 ) in favor of active treatment . The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group , with relative differences of 49 % to 63 % ( P ≤ .0001 ) . Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response . No safety issues were identified . CONCLUSION The results confirm disease modification by SQ-st and ardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis BACKGROUND R and omized trials provide evidence to inform treatment decisions . The Consoli date d St and ards of Reporting Trials ( CONSORT ) Statement is a set of recommendations for the reporting of trials . OBJECTIVE We sought to assess the quality of reporting allergen-specific immunotherapy trials according to CONSORT criteria . METHODS The reporting of the procedure , r and omization , dropouts , strict conduct of intention-to-treat ( ITT ) analysis , and sample size calculation according to CONSORT were assessed in the 46 subcutaneous and 48 sublingual immunotherapy ( SLIT ) blind , placebo-controlled r and omized trials published between 1996 and 2009 in English . RESULTS One subcutaneous immunotherapy ( 2.2 % ) and 3 SLIT ( 6.6 % ) trials met CONSORT Statement criteria . These were used for the registration of sublingual tablets to the European Medicines Agency . In subcutaneous immunotherapy , 16 ( 35 % ) studies reported a CONSORT flow chart , and 12 ( 26 % ) provided a description of dropouts . Adequate r and omization was reported in 9 ( 35 % ) studies , and incomplete r and omization was reported in 15 ( 33 % ) . Power analysis was reported in 15 ( 33 % ) studies . In SLIT , 20 ( 42 % ) studies reported a CONSORT flow chart , and 16 ( 32 % ) a description of dropouts . ITT analysis was carried out in 1 ( 2.2 % ) SLIT study , and a modified ITT analysis was used in 1 ( 2.2 % ) subcutaneous immunotherapy study and 2 ( 4.4 % ) SLIT studies . Adequate r and omization was reported in 6 ( 12 % ) studies , and incomplete r and omization was reported in 16 ( 32 % ) . Power analysis was reported in 15 ( 27 % ) studies . CONCLUSION As in other areas of medicine , the quality of reporting of most immunotherapy trials is low , and only 4.2 % of SLIT r and omized controlled trials met all of the criteria of the CONSORT Statement . Use of the CONSORT criteria should be encouraged BACKGROUND It has long been assumed that allergic rhinitis leads to daytime sleepiness and a deterioration of nocturnal sleep , yet systematic studies have only been rarely conducted in this field . OBJECTIVE The aim of the present study was to investigate the effects of seasonal allergic rhinitis on subjective and objective sleep patterns , quality of life , and daytime sleepiness in otherwise healthy subjects in comparison with nonallergic volunteers . METHODS Twenty-five patients with seasonal allergic rhinitis and 25 healthy volunteers were enrolled in this prospect i ve , controlled clinical trial . Daytime sleepiness and quality of life were assessed with the help of question naires ( Epworth Sleepiness Scale , SF-36 ) ; 2 consecutive nights of fully attended polysomnography were performed before and during the pollen season of 2002 . RESULTS Statistically significant differences between groups were found in respect to changes in daytime sleepiness and selected parameters of quality of life . Impairment of daytime sleepiness and quality of life were related to the severity of the disease . Statistically significant differences were also found for selected parameters of the sleep studies , although the changes were only minimal , and all values were within normal ranges . CONCLUSION Seasonal allergic rhinitis leads to increased daytime sleepiness , as well as to an impairment of quality of life , depending on the severity of the disease . Objective measurements revealed a statistically significant influence of seasonal allergic rhinitis on selected sleep parameters , but changes were not of clinical relevance . Daytime sleepiness seems to be related to the condition itself rather than to an impairment of nocturnal sleep BACKGROUND Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale r and omized , double-blind , placebo-controlled trial . OBJECTIVE We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-st and ardized grass allergy immunotherapy tablet Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU ; ALK-Abelló , Hørsholm , Denmark ) . METHODS A r and omized , double-blind , placebo-controlled , phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications . The analysis set comprised 257 subjects at the follow-up . Efficacy end points were rhinoconjunctivitis symptom and medication scores , quality of life , and percentages of symptom and medication free days . Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor . Safety was assessed based on adverse events . RESULTS Significant improvements in efficacy were consistently shown during 3 years ' treatment . One year after treatment , the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores ( 26 % , P < .001 ) and medication scores ( 29 % , P = .022 ) when compared with placebo . This level was similar to the efficacy observed during the 3-year treatment period . The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment . The active group also reported sustained and significant improvements in quality of life . Sustained clinical benefit was accompanied by immunologic changes . No safety issues were identified . CONCLUSION Three years of treatment with the SQ-st and ardized grass allergy immunotherapy tablet result ed in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment , which is indicative of disease modification and associated long-term benefits |
10,387 | 27,142,791 | Discussion The findings obtained from this systematic review should inform whether disparity exists in the provision of post-arrest care for the elderly ( ≥ 65 years old ) with OHCA or not .
Addressing this problem has a potential to substantially increase the number of > 65-year-old , long-term survivors .
The results of our review might also point to the gaps in the published literature that specifically examines disparity in provision of care for this population . | Background Out-of-hospital cardiac arrest ( OHCA ) is a significant cause of death in developed countries .
The majority of OHCA patients are elderly ( ≥65 years ) , and it was documented that they were less likely than younger patients to receive the evidence -based interventions , even though the improvement in survival in the elderly age group was higher than in younger population .
Our goal is to investigate any disparity in the provision of post-arrest care for the elderly with OHCA and a sustained return of spontaneous circulation ( ROSC ) . | Background — The use of antithrombotic medications after ischemic stroke is recommended for deep vein thrombosis prophylaxis and secondary stroke prevention . We assessed the rate of receipt of these therapies among eligible ischemic stroke patients age ≥65 years and determined the effects of age and other patient characteristics on treatment . Methods and Results — The analysis included Medicare fee-for-service beneficiaries discharged with ischemic stroke ( ICD 433.x1 , 434.x1 , 436 ) r and omly selected for inclusion in the Medicare Health Care Quality Improvement Program 's National Stroke Project 1998 to 1999 , 2000 to 2001 . Patients discharged from nonacute facilities , transferred , or terminally ill were excluded . Receipt of in-hospital pharmacological deep vein thrombosis prophylaxis , antiplatelet medication , anticoagulants for atrial fibrillation , and antithrombotic medications at discharge were assessed in eligible patients , stratified by age ( 65 to 74 , 75 to 84 , and 85 + years ) . Descriptive models identified characteristics associated with treatment . Among 31 554 patients , 14.9 % of those eligible received pharmacological deep vein thrombosis prophylaxis , 83.9 % antiplatelet drugs , 82.8 % anticoagulants for atrial fibrillation , and 74.2 % were discharged on an antithrombotic medication . Rates of treatment decreased with age and were lowest for patients ages 85 years or older . Admission from a skilled nursing facility and functional dependence were associated with lower treatment rates . Conclusions — There was substantial underutilization of antithrombotic therapies among elderly ischemic stroke patients , particularly among the very elderly , those admitted from skilled nursing facilities , and patients with functional dependence . The reasons for low use of antithrombotic therapies , including the apparent underutilization of deep vein thrombosis prophylaxis in otherwise eligible patients , require further investigation BACKGROUND Recent guidelines have acknowledged that thrombolysis decreases mortality from acute myocardial infa rct ion ( AMI ) independently of age . The purpose of this study was to determine the age-related rates of thrombolytic administration and in-hospital mortality and the variables related to the use of thrombolytic therapy for patients with AMI . METHODS A prospect i ve cohort analysis involved a registry of 44 acute care Quebec hospitals that enrolled 3741 patients with AMI between January 1995 and May 1996 . The main outcomes of interest were crude and adjusted age-related in-hospital mortality rates and rates of use of thrombolytic therapy . RESULTS In-hospital mortality rates increased dramatically with age from 2.1 % in patients with AMI who were less than 55 years of age to 26.3 % in those who were 85 years of age or older . Overall , 35.8 % of the patients received thrombolysis . There was a pronounced inverse gradient in the use of thrombolysis with age , ranging from 46.2 % in the youngest age group ( < 55 years ) to 9.5 % in the oldest group ( > or = 85 years ) . After adjustment for potential confounders , the older patients remained significantly less likely to receive thrombolytic therapy . Compared with patients who were less than 55 years of age , the odds ratio of receiving thrombolytic therapy was 0.68 ( 95 % confidence interval [ CI ] 0.52 - 0.89 ) for patients aged 65 - 74 years , 0.48 ( 95 % CI 0.35 - 0.65 ) for patients aged 75 - 84 years and 0.13 ( 95 % CI 0.06 - 0.26 ) for patients aged 85 years or more . Other variables related to thrombolytic therapy were diabetes ( odds ratio [ OR ] 0.77 , 95 % CI 0.59 - 1.00 ) , cerebrovascular disease ( OR 0.46 , 95 % CI 0.30 - 0.72 ) , angina ( OR 0.73 , 95 % CI 0.56 - 0.95 ) , typical chest pain ( OR 2.56 , 95 % CI 1.88 - 3.47 ) ; ST elevation ( OR 8.93 , 95 % CI 7.24 - 11.00 ) , Q wave MI ( OR 5.26 , 95 % CI 4.20 - 6.60 ) and increased length of time between onset of symptoms and arrival at hospital . INTERPRETATION Age is an important independent predictor of in-hospital mortality and lower thrombolytic use following AMI . Other studies are required to further evaluate the appropriateness of thrombolytic therapy for elderly patients BACKGROUND Mortality among patients admitted to hospital after out-of-hospital cardiac arrest ( OHCA ) is high . Based on recent scientific evidence with a main goal of improving survival , we introduced and implemented a st and ardised post resuscitation protocol focusing on vital organ function including therapeutic hypothermia , percutaneous coronary intervention ( PCI ) , control of haemodynamics , blood glucose , ventilation and seizures . METHODS All patients with OHCA of cardiac aetiology admitted to the ICU from September 2003 to May 2005 ( intervention period ) were included in a prospect i ve , observational study and compared to controls from February 1996 to February 1998 . RESULTS In the control period 15/58 ( 26 % ) survived to hospital discharge with a favourable neurological outcome versus 34 of 61 ( 56 % ) in the intervention period ( OR 3.61 , CI 1.66 - 7.84 , p=0.001 ) . All survivors with a favourable neurological outcome in both groups were still alive 1 year after discharge . Two patients from the control period were revascularised with thrombolytics versus 30 ( 49 % ) receiving PCI treatment in the intervention period ( 47 patients ( 77 % ) underwent cardiac angiography ) . Therapeutic hypothermia was not used in the control period , but 40 of 52 ( 77 % ) comatose patients received this treatment in the intervention period . CONCLUSIONS Discharge rate from hospital , neurological outcome and 1-year survival improved after st and ardisation of post resuscitation care . Based on a multivariate logistic analysis , hospital treatment in the intervention period was the most important independent predictor of survival CONTEXT R and omized trials provide robust evidence for the impact of pharmacological and interventional treatments in patients with ST-segment elevation and non-ST-segment elevation acute coronary syndromes ( NSTE ACS ) , but whether this translates to changes in clinical practice is unknown . OBJECTIVE To determine whether changes in hospital management of patients with ST-segment elevation myocardial infa rct ion ( STEMI ) and NSTE ACS are associated with improvements in clinical outcome . DESIGN , SETTING , AND PATIENTS In the Global Registry of Acute Coronary Events ( GRACE ) , a multinational cohort study , 44 372 patients with an ACS were enrolled and followed up in 113 hospitals in 14 countries between July 1 , 1999 , and December 31 , 2006 . MAIN OUTCOME MEASURES Temporal trends in the use of evidence -based pharmacological and interventional therapies ; patient outcomes ( death , congestive heart failure , pulmonary edema , cardiogenic shock , stroke , myocardial infa rct ion ) . RESULTS Use of pharmacological medications increased over the study period ( beta-blockers , statins , angiotensin-converting enzyme inhibitors , thienopyridines with or without percutaneous coronary intervention [ PCI ] , glycoprotein IIb/IIIa inhibitors , low-molecular-weight heparin ; all P<.001 ) . Pharmacological reperfusion declined in patients with STEMI by -22 percentage points ( 95 % confidence interval [ CI ] , -27 to -17 ) , whereas primary PCI increased by 37 percentage points ( 95 % CI , 33 - 41 ) . In patients with non-STEMI , rates of PCI increased markedly by 18 percentage points ( 95 % CI , 15 - 20 ) . Rates of congestive heart failure and pulmonary edema declined in both population s : STEMI , -9 percentage points ( 95 % CI , -12 to -6 ) and NSTE ACS , -6.9 percentage points ( 95 % CI , -8.4 to -4.7 ) . In patients with STEMI , hospital deaths decreased by 18 percentage points ( 95 % CI , -5.3 to -1.9 ) and cardiogenic shock by -24 percentage points ( 95 % CI , -4.3 to -0.5 ) . Risk-adjusted hospital deaths declined -0.7 percentage points ( 95 % CI , -1.7 to 0.3 ) in NSTE ACS patients . Six-month follow-up rates declined among STEMI patients : stroke by -0.8 percentage points ( 95 % CI , -1.7 to 0.1 ) and myocardial infa rct ion by -2.8 percentage points ( 95 % CI , -6.4 to 0.9 ) . In NSTE ACS , 6-month death declined -1.6 percentage points ( 95 % CI , -3.0 to -0.1 ) and stroke by 0.7 percentage points ( 95 % CI , -1.4 to 0.1 ) . CONCLUSIONS In this multinational observational study , improvements in the management of patients with ACS were associated with significant reductions in the rates of new heart failure and mortality and in rates of stroke and mycoardial infa rct ion at 6 months Introduction Persistent coma is a common finding after cardiac arrest and has profound ethical and economic implication s. Evidence suggests that therapeutic hypothermia improves neurological outcome in these patients . In this analysis , we investigate whether therapeutic hypothermia influences the length of intensive care unit ( ICU ) stay and ventilator time in patients surviving out-of-hospital cardiac arrest . Methods A prospect i ve observational study with historical controls was conducted at our medical ICU . Fifty-two consecutive patients ( median age 62.6 years , 43 males , 34 ventricular fibrillation ) su bmi tted to therapeutic hypothermia after out-of-hospital cardiac arrest were included . They were compared with a historical cohort ( n = 74 , median age 63.8 years , 53 males , 43 ventricular fibrillation ) treated in the era prior to hypothermia treatment . All patients received the same st and ard of care . Neurological outcome was assessed using the Pittsburgh cerebral performance category ( CPC ) score . Univariate analyses and multiple regression models were used . Results In survivors , therapeutic hypothermia and baseline disease severity ( Acute Physiology and Chronic Health Evaluation II [ APACHE II ] score ) were both found to significantly influence ICU stay and ventilator time ( all P < 0.01 ) . ICU stay was shorter in survivors receiving therapeutic hypothermia ( median 14 days [ interquartile range ( IQR ) 8 to 26 ] versus 21 days [ IQR 15 to 30 ] in the control group ; P = 0.017 ) . ICU length of stay and time on ventilator were prolonged in patients with CPC 3 or 4 compared with patients with CPC 1 or 2 ( P = 0.003 and P = 0.034 , respectively ) . Kaplan-Meier analysis showed improved probability for 1-year survival in the hypothermia group compared with the controls ( log-rank test P = 0.013 ) . Conclusion Therapeutic hypothermia was found to significantly shorten ICU stay and time of mechanical ventilation in survivors after out-of-hospital cardiac arrest . Moreover , profound improvements in both neurological outcome and 1-year survival were observed Background —Acute coronary occlusion is the leading cause of cardiac arrest . Because of limited data , the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial . Using data from the Parisian Region Out of hospital Cardiac ArresT prospect i ve registry , we performed an analysis to assess the effect of an invasive strategy on hospital survival . Methods and Results —Between January 2003 and December 2008 , 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris , France . In 435 patients with no obvious extracardiac cause of arrest , an immediate coronary angiogram was performed at admission followed , if indicated , by coronary angioplasty . At least 1 significant coronary artery lesion was found in 304 ( 70 % ) patients , in 128 ( 96 % ) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation , and in 176 ( 58 % ) of 301 patients without ST-segment elevation . The hospital survival rate was 40 % . Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival , regardless of the postresuscitation ECG pattern ( odds ratio , 2.06 ; 95 % CI , 1.16 to 3.66 ) . Conclusions —Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation . Therefore , our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern R and omized controlled trials support the use of an early invasive strategy in high-risk patients with non-ST-segment elevation ( NSTE ) acute coronary syndromes ( ACS ) . Although risk increases with age , limited data are available to support this strategy in older patients . The aims of this study were to examine temporal trends in the management and outcomes of NSTE ACS in elderly patients and to explore reasons for the lower use of early angiography in the aged population . Data from 11,732 patients with NSTE ACS were collected from 3 consecutive Canadian registries ( ACS I , ACS II , and Global Registry of Acute Coronary Events [GRACE]/GRACE2 ) from 1999 to 2007 . Rates of in-hospital cardiac catheterization , revascularization , infa rct ion or reinfa rct ion , and death were stratified by age ( < 65 , 65 to 74 , and > or = 75 years ) . Although overall , rates of in-hospital catheterization and revascularization increased over time ( p < 0.001 ) , the largest increase occurred in patients aged < 65 years . The strongest independent negative predictor of the use of cardiac catheterization was age > or = 75 years ( adjusted odds ratio 0.45 , 95 % confidence interval 0.37 to 0.56 , p < 0.001 ) . Use of an early invasive approach was associated with a reduction in 1-year mortality across all age groups , but the absolute difference was greatest in patients aged > or = 75 years . The underestimation of risk by physicians ( ascertained in ACS II ) was the most common reason for choosing a conservative strategy . In conclusion , despite an overall increased use of an early invasive strategy , elderly patients with NSTE ACS remain significantly less likely to undergo cardiac catheterization and revascularization and are often erroneously perceived to be at low risk by their physicians . Future studies should determine whether more aggressive treatment of these high-risk elderly patients improves outcomes Background —This study evaluated the prehospital factors associated with better health-related quality of life for survivors of out-of-hospital cardiac arrest . Methods and Results —This prospect i ve , 20-community , cohort study involved consecutive , adult out-of-hospital cardiac arrest patients who survived to 1 year . Patients were contacted by telephone and evaluated for the Health Utilities Index Mark III ( HUI3 ) , which describes health as a utility score on a scale from 0 ( dead ) to 1.0 ( perfect health ) . The 8091 cardiac arrest patients had overall survival rates of 5.2 % to hospital discharge and 4.0 % to 1 year . We successfully contacted and evaluated 268 of 316 ( 84.8 % ) of known 1-year survivors . The median HUI3 score was 0.80 ( interquartile range , 0.50 to 0.97 ) , which compares well with age-adjusted values for the general population ( 0.83 ) . Logistic regression identified 2 factors independently associated with very good quality of life ( HUI3 > 0.90 ) and their odds ratios ( 95 % CIs ) , as follows : age 80 years or older , 0.3 ( 0.1 to 0.84 ) , and citizen-initiated cardiopulmonary resuscitation ( CPR ) , 2.0 ( 1.2 to 3.4 ) ( Hosmer-Lemeshow goodness-of-fit statistic , 0.74 ) . Conclusions —This study is the largest ever conducted for out-of-hospital cardiac arrest survivors , clearly shows that these patients have good quality of life , and is the first to demonstrate that citizen-initiated CPR is strongly and independently associated with better quality of life . These results emphasize the importance of optimizing community citizen CPR readiness . Given the low rate of citizen-initiated CPR in many communities , we believe that local and national initiatives should vigorously promote the practice of byst and er CPR BACKGROUND Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure ( CHF ) . Treatment with amiodarone or an implantable cardioverter-defibrillator ( ICD ) has been proposed to improve the prognosis in such patients . METHODS We r and omly assigned 2521 patients with New York Heart Association ( NYHA ) class II or III CHF and a left ventricular ejection fraction ( LVEF ) of 35 percent or less to conventional therapy for CHF plus placebo ( 847 patients ) , conventional therapy plus amiodarone ( 845 patients ) , or conventional therapy plus a conservatively programmed , shock-only , single-lead ICD ( 829 patients ) . Placebo and amiodarone were administered in a double-blind fashion . The primary end point was death from any cause . RESULTS The median LVEF in patients was 25 percent ; 70 percent were in NYHA class II , and 30 percent were in class III CHF . The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent . The median follow-up was 45.5 months . There were 244 deaths ( 29 percent ) in the placebo group , 240 ( 28 percent ) in the amiodarone group , and 182 ( 22 percent ) in the ICD group . As compared with placebo , amiodarone was associated with a similar risk of death ( hazard ratio , 1.06 ; 97.5 percent confidence interval , 0.86 to 1.30 ; P=0.53 ) and ICD therapy was associated with a decreased risk of death of 23 percent ( 0.77 ; 97.5 percent confidence interval , 0.62 to 0.96 ; P=0.007 ) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population . Results did not vary according to either ischemic or nonischemic causes of CHF , but they did vary according to the NYHA class . CONCLUSIONS In patients with NYHA class II or III CHF and LVEF of 35 percent or less , amiodarone has no favorable effect on survival , whereas single-lead , shock-only ICD therapy reduces overall mortality by 23 percent CONTEXT The health and policy implication s of regional variation in incidence and outcome of out-of-hospital cardiac arrest remain to be determined . OBJECTIVE To evaluate whether cardiac arrest incidence and outcome differ across geographic regions . DESIGN , SETTING , AND PATIENTS Prospect i ve observational study ( the Resuscitation Outcomes Consortium ) of all out-of-hospital cardiac arrests in 10 North American sites ( 8 US and 2 Canadian ) from May 1 , 2006 , to April 30 , 2007 , followed up to hospital discharge , and including data available as of June 28 , 2008 . Cases ( aged 0 - 108 years ) were assessed by organized emergency medical services ( EMS ) personnel , did not have traumatic injury , and received attempts at external defibrillation or chest compressions or resuscitation was not attempted . Census data were used to determine rates adjusted for age and sex . MAIN OUTCOME MEASURES Incidence rate , mortality rate , case-fatality rate , and survival to discharge for patients assessed or treated by EMS personnel or with an initial rhythm of ventricular fibrillation . RESULTS Among the 10 sites , the total catchment population was 21.4 million , and there were 20,520 cardiac arrests . A total of 11,898 ( 58.0 % ) had resuscitation attempted ; 2729 ( 22.9 % of treated ) had initial rhythm of ventricular fibrillation or ventricular tachycardia or rhythms that were shockable by an automated external defibrillator ; and 954 ( 4.6 % of total ) were discharged alive . The median incidence of EMS-treated cardiac arrest across sites was 52.1 ( interquartile range [ IQR ] , 48.0 - 70.1 ) per 100,000 population ; survival ranged from 3.0 % to 16.3 % , with a median of 8.4 % ( IQR , 5.4%-10.4 % ) . Median ventricular fibrillation incidence was 12.6 ( IQR , 10.6 - 5.2 ) per 100,000 population ; survival ranged from 7.7 % to 39.9 % , with a median of 22.0 % ( IQR , 15.0%-24.4 % ) , with significant differences across sites for incidence and survival ( P<.001 ) . CONCLUSION In this study involving 10 geographic regions in North America , there were significant and important regional differences in out-of-hospital cardiac arrest incidence and outcome OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND Cardiac arrest outside the hospital is common and has a poor outcome . Studies in laboratory animals suggest that hypothermia induced shortly after the restoration of spontaneous circulation may improve neurologic outcome , but there have been no conclusive studies in humans . In a r and omized , controlled trial , we compared the effects of moderate hypothermia and normothermia in patients who remained unconscious after resuscitation from out-of-hospital cardiac arrest . METHODS The study subjects were 77 patients who were r and omly assigned to treatment with hypothermia ( with the core body temperature reduced to 33 degrees C within 2 hours after the return of spontaneous circulation and maintained at that temperature for 12 hours ) or normothermia . The primary outcome measure was survival to hospital discharge with sufficiently good neurologic function to be discharged to home or to a rehabilitation facility . RESULTS The demographic characteristics of the patients were similar in the hypothermia and normothermia groups . Twenty-one of the 43 patients treated with hypothermia ( 49 percent ) survived and had a good outcome --that is , they were discharged home or to a rehabilitation facility -- as compared with 9 of the 34 treated with normothermia ( 26 percent , P=0.046 ) . After adjustment for base-line differences in age and time from collapse to the return of spontaneous circulation , the odds ratio for a good outcome with hypothermia as compared with normothermia was 5.25 ( 95 percent confidence interval , 1.47 to 18.76 ; P=0.011 ) . Hypothermia was associated with a lower cardiac index , higher systemic vascular resistance , and hyperglycemia . There was no difference in the frequency of adverse events . CONCLUSIONS Our preliminary observations suggest that treatment with moderate hypothermia appears to improve outcomes in patients with coma after resuscitation from out-of-hospital cardiac arrest AIM OF THE STUDY We investigated implementation and efficacy of mild therapeutic hypothermia in the treatment of out-of-hospital cardiac arrest due to ventricular fibrillation . MATERIAL S AND METHODS Two periods were compared , an historical one ( 36 patients ) between 2000 and 2002 where therapeutic hypothermia was never used , and a recent period ( 32 patients ) between 2003 and 2005 where therapeutic hypothermia ( 32 - 34 degrees C ) was implemented prospect ively in our unit . Cooling was obtained by simply using wet cloths and ice packs . Survival in the two groups and factors associated with survival were analysed , together with the neurological prognosis in discharged patients . RESULTS Survival was significantly higher in the hypothermia group ( 56 % versus 36 % ) , whereas no significant difference was observed in severity between the two periods . Only age , time from return to spontaneous circulation < 20min , and therapeutic hypothermia were independently associated with survival . Therapeutic hypothermia was well tolerated and was associated with a significant improvement in neurological outcome . Whereas only 23 % of patients actually reached the target temperature in 2003 , 100 % did in 2005 . CONCLUSION Therapeutic hypothermia is efficient in significantly improving survival and neurological outcome of out-of-hospital cardiac arrest with ventricular fibrillation . By using a simple method , it can be implemented easily and quickly , without side effects BACKGROUND Previous studies have documented an underuse of evidence -based therapies in patients with acute myocardial infa rct ion ( AMI ) . However , many of these studies failed to consider contraindications to therapy , the effect of age ( ie , elderly vs non-elderly patients ) on use , or both . The objective of this study was to determine whether elderly patients are less likely than non-elderly patients to receive evidence -based AMI treatments , both before and after the consideration of contraindications to therapy . METHODS A retrospective chart review of a r and om sample of 5131 patients with AMI who were admitted to 1 of 44 hospitals in Ontario was conducted for the fiscal years 1994 to 1996 . Using the Canadian Cardiovascular Research Team (CCORT)/Canadian Cardiovascular Society ( CCS ) Quality Indicators for AMI Care , we classified patients as being eligible or ideal ( ie , no contraindications to treatment ) c and i date s to receive aspirin , beta-blockers , thrombolysis , angiotensin-converting enzyme inhibitors ( ACEIs ) , or statins or to undergo lipid profiling . The proportions of eligible and ideal patients who received treatment were calculated , and the latter were compared with benchmarks . RESULTS The median age of the cohort was 69 years ; 63 % were of the patients were aged > or = 65 years . There was underperformance of prescribing treatments in ideal c and i date s relative to benchmarks ( eg , aspirin at discharge : 78.6 % vs 90 % benchmark ) . The odds of ideal ( ie , no contraindications ) elderly c and i date s receiving various evidence -based AMI treatments were consistently less than that of non-elderly patients with AMI , with the exception of ACEIs at discharge ( odds ratio , 1.46 ; 95 % CI , 1.22 - 1.74 ) . CONCLUSIONS Despite adjustments for contraindications to therapy , the underuse of AMI treatments , particularly in elderly patients , was found OBJECTIVE In this study we aim ed to report survival beyond 6 months , including quality of life , for patients after out-of-hospital cardiac arrest ( OHCA ) with a physician-based EMS in an urban area . METHODS We collected data related to OHCA prospect ively during a 2-year period . Long-term survival was determined by cross-referencing our data base with two Danish national registries . Patients older than 18 years who had survived for more than 6 months after OHCA were contacted , and after informed written consent was obtained , an interview was conducted in their home and a question naire on quality of life ( SF-36 ) and the mini mental state examination ( MMSE ) were administered . RESULTS We had data on 984 cases of OHCA . In 512 cases CPR was attempted and at 6 months , a total of 63 patients were alive corresponding to 12.3 % [ 95 % CI : 9.7 - 15.5 % ] of all who were treated . Of the 33 patients examined , the median MMSE was 29 ( 16 - 30 ) and two patients , corresponding to 6 % , [ 95 % CI : 0.7 - 20.6 % ] had an MMSE below 24 . Two out of eight aspects of the SF-36 were significantly worse than national norms at the same age , but none of the summary scores differed significantly . CONCLUSION Survival beyond 6 months was found in 12.3 % OHCA in a physician-based EMS . Summary scores of quality of life were not significantly different from the national norm but 2 out of 8 subscores were lower . Signs of dementia were uncommon as only 6 % had an MMSE score below 24 The major risks associated with coronary disease are angina , acute myocardial infa rct ion , reduced cardiac function as manifest by depressed left ventricular ejection fraction and congestive heartfailure , and sudden arrhythmogenic cardiac death . During the past three decades , considerableadvances have been made in the management of patients with coronary heart disease with beta-blockers , calcium-channel blockers , angiotensin converting-enzyme ( ACE ) inhibitors , angiotensin receptor blockers , thrombolytics , balloon-stentangioplasty , and coronary artery bypass graftsurgery . The clinical course of patients with coronary disease has been meaningfully improved by these therapies , but sudden cardiac death remains a major problem and has not been impacted by these therapeutic interventions . Recently , the Center for Disease Control reported that more than 460 000 sudden cardiac deaths occur annually in the U.S. , with sudden cardiac death accounting for 63 % of all cardiac mortality events.1 Following the introduction of the implanteddefibrillator in 1980 , the defibrillator was initially utilized as secondary prevention for patients with aborted cardiac arrest or documented life-threatening ventricular tachycardia . In 1991 , the Cardiac Arrhythmia Suppression Trial (CAST)investigators reported the ineffectiveness and actual harm associated with several promisingantiarrhythmic drugs that were being used toimprove survival in cardiac patients with manifest ventricular arrhythmias.2 That same year , ourMulticenter Automatic Defibrillator Implantation Trial ( MADIT ) research group initiated the firstr and omized trial to determine if an implantedcardioverter defibrillator ( ICD ) would save lives in coronary patients with prior myocardial infa rct ion , reduced ejection fraction , non-sustained ventricular OBJECTIVE To assess whether advanced age is an independent predictor of survival to hospital discharge in community-dwelling adult patients who sustained an out-of-hospital cardiac arrest in a suburban county . METHODS A prospect i ve cohort study was conducted in a suburban county emergency medical services system of community-dwelling adults who had an arrest from a presumed cardiac cause and who received out-of-hospital resuscitative efforts from July 1989 to December 1993 . The cohorts were defined by grouping ages by decade : 19 - 39 , 40 - 49 , 50 - 59 , 60 - 69 , 70 - 79 , and 80 or more . The variables measured included age , gender , witnessed arrest , response intervals , location of arrest , documented byst and er cardiopulmonary resuscitation , and initial rhythms . The primary outcome was survival to hospital discharge . Results are reported using analysis of variance , chi square , and adjusted odds ratios from a logistic regression model . Age group 50 - 59 served as the reference group for the regression model . RESULTS Of the 2,608 total presumed cardiac arrests , the overall survival rate to hospital discharge was 7.25 % . Patients in age groups 40 - 49 and 50 - 59 experienced the best rate of successful resuscitation ( 10 % ) . Each subsequent decade had a steady decline in successful outcome : 8.1 % for ages 60 - 69 ; 7.1 % for ages 70 - 79 ; and 3.3 % for age 80 + . In a post-hoc analysis , further separation of the older age group revealed a successful outcome in 3.9 % of patients ages 80 - 89 and 1 % in patients 90 and older . Patients aged 80 years or more were more likely to arrest at home , were more likely to have an initial bradyasystolic rhythm , yet had a similar rate of resuscitation to hospital admission . In the regression model , age 80 or older was associated with a significantly worse survival to hospital discharge ( OR = 0.4 , 95 % CI = 0.20 to 0.82 ) . CONCLUSIONS There was a twofold decrease in survival following out-of-hospital cardiac arrest to discharge in patients aged 80 or more when compared with the reference group in this suburban county setting . However , resuscitation for community-dwelling elders aged 65 - 89 is not futile . These data support that out-of-hospital resuscitation of elders up to age 90 years is not associated with a universal dismal outcome BACKGROUND There are limited data on the recent trend in the use of optimal evidence -based medical therapies after acute coronary syndromes ( ACSs ) . We sought to evaluate ( 1 ) the temporal changes in medical management of patients discharged after an ACS ; ( 2 ) patient and practice characteristics associated with optimal medical therapy at discharge ; and ( 3 ) the association between discharge medication use and 1-year outcome . METHODS The Canadian ACS I ( September 1999-June 2001 ) and ACS II ( October 2002-December 2003 ) Registries were prospect i ve , multicenter , observational studies of 6853 patients admitted for ACS . We examined the discharge use of medications among 5833 hospital survivors who did not have any contraindications to antiplatelet/anticoagulant , beta-blocker , angiotensin-converting enzyme inhibitor , or lipid-modifying therapies . Optimal medical therapy was defined as the use of all indicated medications . Follow-up data at 1 year were collected by telephone interview . We performed hierarchical logistic regression to identify patient characteristics and care patterns associated with optimal medical treatment and to examine its relationship with 1-year mortality . RESULTS There were significant increases in the discharge use of all 4 classes of medications over time ; 28.9 % and 51.8 % of patients in ACS I and ACS II Registries , respectively , were prescribed optimal medical therapy ( P < .001 ) . Advanced age , female sex , prior heart failure , renal dysfunction , and coronary bypass surgery during hospitalization were negative independent predictors of optimal medical therapy . Conversely , enrollment in ACS II Registry , history of dyslipidemia , presence of ST elevation and abnormal cardiac biomarker , previous myocardial infa rct ion , and previous coronary revascularization were independently associated with the use of combination therapy . After adjusting for other vali date d prognosticators , patients receiving optimal medical therapy had significantly lower 1-year mortality ( adjusted odds ratio 0.54 , 95 % confidence interval 0.36 - 0.81 , P = .003 ) compared with those given 0 or 1 drug at discharge . Over the 1-year follow-up period , substantial numbers of patients discontinued therapies , whereas others were initiated on treatment . CONCLUSIONS Despite the temporal increases in the combined use of evidence -based pharmacologic therapies , which is associated with improved outcome , medical management of ACS remains suboptimal . Quality improvement strategies are needed to enhance the appropriate use of effective therapies , targeting specifically the high-risk but undertreated patients who may derive the greatest therapeutic benefit |
10,388 | 21,118,575 | Conclusions Studies which used a multi-faceted approach had the largest and most sustained reductions in benzodiazepines use .
It appears that support groups for patients , non-voluntary recruitment of GPs , and oral delivery of alerts or feedback may all improve the outcomes of interventions .
The choice of outcome measures , delivery style of educational messages , and requests by GPs to stop benzodiazepines , either in a letter or face to face , showed no differences on the success rates of the intervention | Background Benzodiazepines are often used on a long term basis in the elderly to treat various psychological disorders including sleep disorders , some neurological disorders and anxiety .
This is despite the risk of dependence , cognitive impairment , and falls and fractures .
Guidelines , campaigns and prescribing restrictions have been used to raise awareness of potentially inappropriate use , however long term use of benzodiazepine and related compounds is currently increasing in Australia and worldwide .
The objective of this paper is to explore interventions aim ed at improving the prescribing and use of benzodiazepines in the last 20 years . | OBJECTIVE To assess the impact and cost-effectiveness of two information-based provider reminder interventions design ed to improve self-care management and outcomes of heart failure ( HF ) patients . DATA SOURCES / STUDY SETTING Interview and agency administrative data on 628 home care patients with a primary diagnosis of HF . STUDY DESIGN Patients were treated by nurses r and omly assigned to usual care or one of two intervention groups . The basic intervention was an e-mail to the patient 's nurse highlighting six HF-specific clinical recommendations . The augmented intervention supplemented the initial nurse reminder with additional clinician and patient re sources . DATA COLLECTION Patient interviews were conducted 45 days post admission to measure self-management behaviors , HF-specific outcomes ( Kansas City Cardiomyopathy Question naire-KCCQ ) , health-related quality of life ( EuroQoL ) , and service use . PRINCIPAL FINDINGS Both interventions improved the mean KCCQ summary score ( 15.3 and 12.9 percent , respectively ) relative to usual care ( p < or = .05 ) . The basic intervention also yielded a higher EuroQoL score relative to usual care ( p < or = .05 ) . In addition , the interventions had a positive impact on medication knowledge , diet , and weight monitoring . The basic intervention was more cost-effective than the augmented intervention in improving clinical outcomes . CONCLUSIONS This study demonstrates the positive impact of targeting evidence -based computer reminders to home health nurses to improve patient self-care behaviors , knowledge , and clinical outcomes . It also advances the field 's limited underst and ing of the cost-effectiveness of selected strategies for translating research into practice Background The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting . Methods Twenty facilities took part in a r and omized controlled trial with a seven month follow-up period . Two outreach visits were delivered by a pharmacist . At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates , psychotropic drug prescribing and stroke risk reduction practice s ( BP monitoring , aspirin and warfarin use ) for the facility relevant to the physician . The effect of the interventions was determined via pre- and post-intervention case note audit . Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications . Chi-square tests , independent sample s t-test , and logistic regression were used in the analysis . Results Data were available from case notes at baseline ( n = 897 ) and seven months follow-up ( n = 902 ) , 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits . Pre- and post-intervention data were available for 715 participants . There were no differences between the intervention and control groups for the three month fall rate . We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention . The exception was significantly greater use of " as required " antipsychotics in the intervention group compared with the control group after the pharmacy intervention ( RR = 4.95 ; 95%CI 1.69–14.50 ) . There was no statistically significant difference between groups for the numbers of patients " at risk of stroke " on aspirin at follow-up . Conclusions While the strategy was well received by the physicians involved , there was no change in prescribing patterns . Patient care in residential setting s is complex and involves contributions from the patient 's physician , family and residential care staff . The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained BACKGROUND Benzodiazepine use by elderly patients is associated with adverse outcomes including increased risk of falls and fractures , motor vehicle accidents and cognitive impairment . Recent studies suggest that individualized feedback and education to physicians may improve drug prescribing . In this study , we evaluated an intervention to address the inappropriate prescribing of benzodiazepines for elderly patients . METHODS We identified 1624 primary care physicians who wrote at least 10 prescriptions for the target drugs in a 2-month period and r and omly assigned these physicians to the intervention group or the control group . We obtained data from the Ontario Drug Benefit cl aims data base , which covers all Ontario residents aged 65 years and over for drugs selected from a minimally restrictive formulary . Every 2 months for 6 months , confidential profiles of benzodiazepine prescription use coupled with evidence -based educational bulletins were mailed to the intervention group . The control group received feedback and educational bulletins about first-line antihypertension drug prescribing for elderly patients . Our main outcome measures were reductions in the proportion of each physician 's total benzodiazepine prescriptions for long-acting agents , combinations of benzodiazepines with other psychoactive medications ( including other benzodiazepines ) and long-term benzodiazepine therapy . RESULTS After r and omization , 168 physicians agreed to be in the intervention group and 206 in the control group . Their demographic and prescribing characteristics were similar . Although the proportion of long-acting benzodiazepine prescriptions decreased by 0.7 % in the intervention group between the baseline period and the end of the intervention period ( from 20.3 % , or a mean of 29.5 prescriptions , to 19.6 % , or a mean of 27.7 prescriptions ) and increased by 1.1 % in the control group ( from 19.8 % , or a mean of 26.4 prescriptions , to 20.9 % , or a mean of 27.7 prescriptions ) ( p = 0.036 ) , this difference was not clinical ly significant . There was no significant difference over the study period in either combination prescribing of benzodiazepines or in prescriptions for long-term benzodiazepine therapy . INTERPRETATION We did not find that a program of confidential feedback and educational material offered to Ontario primary care physicians had a clinical ly significant impact on their benzodiazepine prescribing Background Early identification of permanent hearing impairment in children enables appropriate intervention which reduces adverse developmental outcomes . The UK Government has introduced a universal hearing screening programme for neonates . All involved health professionals , including those in Primary Care , need to be aware of the service to enable them to offer appropriate support to their patients . A programme of information dissemination within Primary Care was therefore undertaken . The aim of the current study was to determine the extent to which the information had reached General Practitioners ( GPs ) , the GPs ' preferred mode of dissemination and the sources from which GPs accessed information Methods Postal question naire survey of a r and omised sample of 1000 GPs in the Phase I pilot sites of the Neonatal Hearing Screening Programme ( NHSP ) . Results Responses were received from 54.2 % of the sample . Just under 50 % of those responding had received information , 62.2 % of respondents said they would like to receive more information and the preferred methods of dissemination were the written word and web-sites to allow access when needed . Few GPs perceive themselves to have a core role in the delivery of the NHSP and thence a need for knowledge in the subject . Many are keen to delegate detail to a third party , usually the health visitor , who has traditionally had responsibility for hearing screening . Conclusions Dissemination efforts for service developments of relevance to GPs should concentrate on advertising a website address via brief but memorable posted literature and /or articles in relevant journals and magazines . The website should be GP-friendly , and have a dedicated area for GPs including information of specific relevance and downloadable information sheets OBJECTIVE To determine the extent of self-reported use of prescription medications in an Australian community sample . DESIGN , SETTING AND PARTICIPANTS Face-to-face interviews with a r and om , representative sample of the South Australian population ( aged > or = 15 years ) living in metropolitan and rural areas . The study , a Health Omnibus Survey , was conducted between March and June 2004 . MAIN OUTCOME MEASURES Reported number of prescribed medications used per person , most common categories of medication , and use by individuals of multiple medications for the same body system . RESULTS From 4700 households selected , 3015 participants were interviewed ( 65.9 % response rate ) . Of respondents , 46.8 % were using prescribed medications ; 171 respondents ( 5.7 % ) were taking six or more medications , and four were taking 16 or more ; 23.2 % were using medications for the cardiovascular system , with 11.9 % using agents acting on the renin-angiotensin system . Prescription medication use increased with age , with over 10 % of respondents aged > or = 55 years using six or more medications . CONCLUSIONS Use of multiple prescribed medications was common , with the potential for significant drug interactions . Assuming a similar pattern of medication use Australia-wide , reducing the number of prescribed medications by one for people taking six or more medications would save the federal government about 380 million dollars a year BACKGROUND Despite ongoing concern about adverse effects and dependence on benzodiazepines , approximately 2 % of Australians are still taking them on a regular basis . The aim of this study was to evaluate the effectiveness of an educational outreach or ' academic detailing ' program about prescribing of benzodiazepines . METHOD In this r and omised trial general practice registrars ( n = 157 ) in New South Wales were allocated to an intervention group ( n = 79 ) , which received a 20 minute educational outreach visit ; or a control group ( n = 78 ) which received an intervention on an unrelated topic . Prescribing behaviour was monitored by a pre-intervention and two post-intervention practice activity surveys . MAIN OUTCOME MEASURES These were the rate of benzodiazepine prescribing for all indications , for anxiety and for sleep disorders . RESULTS Overall benzodiazepine prescribing by the intervention group declined from 2.3 to 1.7 per 100 encounters , while the control group also declined from 2.2 to 1.6 per 100 encounters . Analysis of variance showed this was a significant drop over time ( P = 0.042 ) but there was no difference between groups ( P = 0.99 ) . The prescribing decrease observed was in continuing rather than initial prescriptions . CONCLUSIONS A marked decrease in benzodiazepine prescribing was seen over the course of the study in both intervention and control groups but no differential effect due to the educational outreach visit was found OBJECTIVE To describe how general practitioners use computers for clinical purpose s. DESIGN Mail survey of a cross-sectional national stratified r and om sample of 3000 GPs in primary care setting s between 10 October and 31 December 2005 . MAIN OUTCOME MEASURES Use of computers , and use of computerised clinical functions such as prescribing , medication checking , generating health summaries , running recall systems , and writing progress notes . RESULTS Of 1186 GPs responding ( 39.5 % response rate ) , 90 % used a clinical software package . GPs used clinical packages for prescribing ( 98 % ) , checking for drug-drug interactions ( 88 % ) , recording a reason for prescribing ( 65 % ) , to order laboratory tests ( 85 % ) , run recall systems ( 78 % ) , and record progress notes ( 64 % ) . Less frequently used functions included generating lists of patients needing vaccines ( 43 % ) and taking the same medication ( 39 % ) . Less than 20 % of GPs who used a clinical package accessed computerised information during the consultation . CONCLUSIONS Australian general practice has achieved near-universal clinical computerisation . Electronic prescribing alone has probably improved efficiency and quality of care , and reduced medication errors . Increasing the use of other functions , such as accessing online decision support and maintaining registries of patients , is likely to lead to further health gains , especially in managing chronic conditions INTRODUCTION Adverse drug events ( ADEs ) are associated with inappropriate prescribing ( IP ) and result in increased morbidity , mortality and re source utilisation . We used Beers ' Criteria to determine the three-month prevalence of IP in a non-selected community-dwelling population of acutely ill older people requiring hospitalisation . METHODS A prospect i ve , observational study of 597 consecutive acute admissions was performed . Diagnoses and concurrent medications were recorded before hospital physician intervention , and Beers ' Criteria applied . RESULTS Mean patient age ( SD ) was 77 ( 7 ) years . Median number of medications was 5 , range 0 - 13 . IP occurred in 32 % of patients ( n = 191 ) , with 24 % , 6 % and 2 % taking 1 , 2 and 3 inappropriate medications respectively . Patients taking > 5 medications were 3.3 times more likely to receive an inappropriate medication than those taking < or = 5 medications ( OR 3.34 : 95 % , CI 2.37 - 4.79 ; P<0.001 ) . Forty-nine per cent of patients with inappropriate prescriptions were admitted with adverse effects of the inappropriate medications . Sixteen per cent of all admissions were associated with such adverse effects . CONCLUSION IP is highly prevalent in acutely ill older patients and is associated with polypharmacy and hospitalisation . However , Beers ' Criteria can not be used as a gold st and ard as they do not comprehensively address all aspects of IP in older people OBJECTIVE : To determine whether reminder cards in medical records enhance the effectiveness of audit with feedback in improving the care of patients taking long term benzodiazepine drugs . DESIGN : R and omised trial , practice s receiving feedback only in one group and practice s receiving feedback plus reminder cards in the other group . SETTING : 18 general practice s in Leicestershire . SUBJECTS : R and om sample s of patients who had been taking a benzodiazepine anxiolytic or hypnotic drug for four weeks or longer . MAIN OUTCOME MEASURES : Entries in medical records indicating compliance with five criteria of care : assessment of suitability for withdrawal ; being told about dependency ; withdrawal being recommended ; withdrawal or continuing medication ; and a consultation with the general practitioner in the past year . Data were collected before and after feedback or feedback plus reminders . RESULTS : Of a total population of 125,846 registered with the 18 practice s , 2409 ( 1.9 % ) had been taking a benzodiazepine for four weeks or longer . Of the 742 in the first sample s , 543 ( 73.2 % ) were women , the mean ( SD ) age was 68.7 ( 14.9 ) years , and they had been taking a benzodiazepine for 10.1 ( 6.7 ) years . The number of patients whose care complied with the criteria rose after the interventions to implement change . The increase was greater in practice s receiving feedback plus reminders for only two of the five criteria " told about dependency " increasing from 52 ( 11.1 % ) to 118 ( 25.8 % ) in the feedback only group , and from 27 ( 10.5 % ) to 184 ( 43.0 % ) in the feedback plus reminders group ; odds ratio ( OR ) 1.46 ( 95 % confidence interval ( 95 % CI ) 1.32 to 5.21 ) ; and " consulted in the past year " increasing from 434 ( 93.1 % ) to 411 ( 95.8 % ) in the feedback only group and 255 ( 96.6 % ) to 400 ( 99.8 % ) in the feedback plus reminders group , OR ( 95 % CI ) 13.5 ( 2.01 to 330.3 ) . CONCLUSIONS : Reminder cards had only a limited effect and can not be recommended for routine use . There were improvements in the care of patients of both groups of practice s and further studies are indicated to determine the impact of both systematic ally developed criteria and reminders embedded into restructured medical records BACKGROUND Although psychoactive medications have substantial side effects in the elderly , these drugs are used frequently in nursing homes . Few interventions have succeeded in changing this situation , and little is known about the clinical effects of such interventions . METHODS We studied six matched pairs of nursing homes ; at one r and omly selected nursing home in each pair , physicians , nurses , and aides participated in an educational program in geriatric psychopharmacology . At base line we determined the type and quantity of drugs received by all residents ( n = 823 ) , and a blinded observer performed st and ardized clinical assessment s of the residents who were taking psychoactive medications . After the five-month program , drug use and patient status were reassessed . RESULTS Scores on an index of psychoactive-drug use , measuring both the magnitude and the probable inappropriateness of medication use , declined significantly more in the nursing homes in which the program was carried out ( experimental nursing homes ) than in the control nursing homes ( decrease , 27 percent vs. 8 percent ; P = 0.02 ) . The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes ( 32 percent vs. 14 percent ) ; the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent , and for antihistamine hypnotics , 45 percent vs. 21 percent . In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities , but they were more likely to report depression . Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory . Most other measures of clinical status remained unchanged in both groups . CONCLUSIONS An educational program targeted to physicians , nurses , and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents A r and omised controlled trial studied the effect of an educational visit on benzodiazepine prescribing . An approximately representative sample of 286 general practitioners was allocated to an intervention or a control group . Rates of benzodiazepine prescriptions were derived from two comprehensive self-report surveys seven months apart . Two months after the first survey the intervention group received an educational visit and supporting material from a doctor or pharmacist , ostensibly unconnected with the surveys . The overall benzodiazepine prescribing rate fell by 23.7 per cent from the first to the second surveys , from 4.93 to 3.76 prescriptions per 100 encounters ( P < 0.001 ) . Anxiety and insomnia diagnosis rates also declined from 4.68 to 3.76 per 100 encounters ( 19.7 per cent ) . After adjusting for confounders , there was a differential downward trend in prescriptions per diagnosis of insomnia but not to a statistical level . The same was true of initial prescriptions per insomnia diagnosis . In a subsidiary analysis selecting only new insomnia diagnoses , the intervention had a strong effect in reducing initial prescriptions ( odds ratio 0.18 , 95 per cent confidence interval 0.04 to 0.73 ) . No effect was seen on prescribing for anxiety diagnoses . Educational practice visiting for benzodiazepine prescribing in anxiety , as we conducted it , is not justified in an unselected population of general practitioners . Specific education on prescribing for insomnia is probably useful . Our interpretation of the reduction in benzodiazepine prescribing is that probably there was an effect from self-monitoring alone which overwhelmed a main- analysis intervention effect . Retrospective diagnosis may also have obscured a real intervention effect BACKGROUND Different methods have previously been tested to affect GPs ' prescribing habits . Attention has been drawn to benzodiazepines and antipsychotic drugs that are associated with several adverse effects in the elderly . OBJECTIVE To evaluate if educational outreach visits to GP practice s can affect the prescribing of benzodiazepines and antipsychotic drugs to the elderly and to evaluate the opinions of the participating GPs on such education . METHODS In the county of Skåne , Sweden , 41 GP practice s were invited to participate in educational outreach visits . Fifteen GP practice s accepted the invitation . Practice s were r and omised to active ( 8 practice s , 23 physicians ) and control group ( 7 practice s , 31 physicians ) . After the educational outreach visits prescribing of benzodiazepines and antipsychotic drugs to patients 65 years or older were measured for 1 year . The control group participated in the education after the study period . The opinions of GPs on educational outreach visits were evaluated . RESULTS One year after the educational outreach visits there were significant decreases in the active group compared to control group in the prescribing of medium- and long-acting benzodiazepines and total benzodiazepines but not so for antipsychotic drugs . CONCLUSIONS Educational outreach visits can be effective in modifying GPs ' prescribing habits . We have shown this to be so for prescribing of benzodiazepines to elderly patients in primary health care . Educational outreach visits are also very well appreciated by participating GPs AIMS To evaluate whether a year long clinical pharmacy program involving development of professional relationships , nurse education on medication issues , and individualized medication review s could change drug use , mortality and morbidity in nursing home residents . METHODS A cluster r and omised controlled trial , where an intervention home was matched to three control homes , was used to examine the effect of the clinical pharmacy intervention on resident outcomes . The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensl and and north-east New South Wales , Australia . The outcome measures were : continuous drug use data from government prescription subsidy cl aims , cross-sectional drug use data on prescribed and administered medications , deaths and morbidity indices ( hospitalization rates , adverse events and disability indices ) . RESULTS This intervention result ed in a reduction in drug use with no change in morbidity indices or survival . Differences in nursing home characteristics , as defined by cluster analysis with SUDAAN , negated intervention-related apparent significant improvements in survival . The use of benzodiazepines , nonsteroidal anti-inflammatory drugs , laxatives , histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group , whereas the use of digoxin and diuretics remained similar to controls . Overall , drug use in the intervention group was reduced by 14.8 % relative to the controls , equivalent to an annual prescription saving of A64 dollars per resident ( approximately 25 pound sterling ) . CONCLUSIONS This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure . The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study , and even more so using additional instruments specific for measuring outcomes related to changes in drug use OBJECTIVE To determine whether weekly e-mails of structured , critically appraised summaries of new articles , within the format of a Weekly Browsing Journal Club ( WBJC ) , would encourage use of evidence in practice . DESIGN R and omised controlled trial . METHOD A sample of 107 academic general internists were r and omly assigned to receive either the WBJC ( n = 54 ) or a health news website ( n = 53 ) by e-mail on a weekly basis for 3 months . Participants completed a pre- and post-intervention question naire that measured their use of evidence in practice , attitudes about the role of evidence in practice , critical appraisal ability and reading habits . RESULTS Of 107 participants , 90 % completed the trial . At baseline , when faced with questions , they found answers on which to base their clinical decisions 67 % of the time . Participants incorporated evidence into patient care for 60 % of patients and read evidence to help make decisions for 25 % . After 3 months , the groups did not differ in the use of evidence in practice . Changes in attitudes toward the role of evidence in practice and in self-perceived critical appraisal ability were also similar . The subjects spent 2.2 hours reading 4.3 journals per week . Weekly reading time decreased by 10 minutes in the WBJC group , but increased by 26 minutes in the control group ( P = 0.02 ) . At study completion , 82 % of the WBJC group were satisfied with the intervention and 90 % asked to continue . CONCLUSION While doctors appreciated these summaries , which improved their reading efficiency , the intervention had little impact on their use of research evidence in practice AIM This study set out to assess the effect of a letter from the general practitioner , suggesting a reduction in the use of benzodiazepines , and whether the impact of the letter could be increased by the addition of information on how to tackle drug reduction . METHOD Two hundred and nine long-term users of benzodiazepines in general practice were divided into three groups : two intervention groups and a control group . The first intervention group received a letter from their general practitioner asking that benzodiazepine use be gradually reduced and perhaps , in time , stopped . The second intervention group received the same letter plus four information sheets at monthly intervals , design ed to assist drug reduction : The mean age of the 209 people was 69 years ( age range 34 - 102 years ) . RESULTS After six months , both intervention groups had reduced their consumption to approximately two thirds of the original intake of benzodiazepines and there was a statistically significant difference between the intervention groups and the control group . Eighteen per cent of those receiving the interventions received no prescriptions at all during the six month monitoring period . CONCLUSION The results indicate that a simple intervention can have a considerable effect on the use of hypnotic and anxiolytic drugs , even with a sample of elderly users To investigate the potential benefits of two modes of evidence -based knowledge transfer ( ' active ' and ' passive ' modes ) in terms of improvement of intention of prescription , knowledge , and real prescription in practice , we performed an open r and omized controlled trial ( CardioDAS ) using a factorial design ( two tested interventions : ' active ' and ' passive ' knowledge transfer ) and a hierarchical structure ( cluster of physicians for each department level ) . The participants were cardiologists working in French public hospitals . In the ' passive ' transfer group , cardiologists received evidence -based knowledge material ( available on Internet ) every week for a duration of 1 year . In the ' active ' transfer group , two knowledge brokers ( EA , PN ) visited the participating departments ( every 2 months for 1 year , 2 h per visit ) . The primary outcome consisted in the adjusted absolute mean variation of score ( difference between post- and pre- study session ) of answers to simulated cases assessing the intention to prescribe . Secondary outcomes were the variation of answers to a multiple-choice question naire ( MCQ ) assessing knowledge and of the conformity of real prescriptions to evidence -based reference assessing the behavioral change . Twenty-two French units ( departments ) of cardiology were r and omized ( 72 participating cardiologists ) . In the ' active ' transfer group , the primary outcome was more improved than that in the control ( P = 0.031 at the department level , absolute mean improvement of 5 points/100 ) . The change in knowledge transfer ( MCQ ) was also significant ( P = 0.039 at the department level , absolute mean improvement of 6 points/100 ) . However , no benefit was shown in terms of prescription conformity to evidence . For the ' passive ' mode of knowledge transfer and for the three outcomes considered , no improvement was identified . CardioDAS findings confirm that ' active ' knowledge transfer has some impact on participants ' intent to prescribe and knowledge , but no effect on behavioral outcome . ' Passive ' transfer seems far less efficient . In addition , the size of the benefit remains small and its consequences limited in practice Minimal intervention strategies to decrease long-term benzodiazepine use have not yet been evaluated in large primary care based studies with a blinded control condition and a long follow-up period . The purpose of this study was to assess the effects of a letter with a discontinuation advice sent to long-term benzodiazepine users in family practice followed by an evaluation consultation offer . The experimental group consisted of 2425 long-term benzodiazepine users , 1707 of whom were addressed by a discontinuation letter and an evaluation consultation offer . The control group consisted of 1821 long-term users . Primary endpoints were the number of prescribed daily dosages ( PDD ) and the percentage of subjects without prescription ( quitters ) . At 21 months a reduction in benzodiazepine prescription of 26 % was observed in the experimental group , versus 9 % in the control group ( PDD difference=12.5 ; 95%-ci : 8.2 - 16.8 ) . In the experimental group 13 % and in the control group 5 % of the study completers were benzodiazepine prescription free through the full follow-up period ( RR=2.6 ; 95%-ci : 2.0 - 3.4 ) . The percentage of quitters at short-term ( 6 months ) was 24 % in the experimental group versus 12 % in the control group ( RR=2.1 ; 95%-ci : 1.8 - 2.4 ) . It is concluded that this intervention strategy steadily reduces long-term benzodiazepine use in family practice Objective : Many patients with depression who attend primary care are not detected and are unaware of the benefits of therapeutic intervention . Our aim is to evaluate the recognition and management of depressed patients presenting in primary care in Spain . Methods : This was a two-phase cross-sectional study in primary care centers in Tarragona ( Spain ) . In the first phase , we screened 906 consecutive patients using the Zung 's Self-Rating Depression Scale . In the second phase , all 209 patients whose results were positive and 97 patients whose results were negative ( 1/7 at r and om ) were given the Structured Clinical Interview for DSM-IV Disorders , a series of question naires , and the judgment of the physician about the presence of depression was determined . In the 120 patients with major depression and /or dysthymia , predictors of detection and treatment of depression were determined . Results : Seventy-two percent of depressed patients were detected . The detection was associated with educational level , severity of the depression , level of impairment , and the complaint of explicit psychological symptoms . Thirty-four percent were receiving treatment with antidepressants . Antidepressant treatment was associated with marital status , severity of and impairment from the depression , frequency of visits to the family physician , and the patients ' complaint of psychological symptoms . Conclusion : Many depressed patients are not detected , but these are often the patients who present with the mildest forms of depression and for whom the benefits of detection are far from clear . Although treatment was associated with the severity of depression , most depressed patients , at any level of seriousness , do not receive appropriate treatment In order to measure the effect of industry-independent information on the prescribing of benzodiazepines in general practice , 128 primary practitioners were r and omly allocated to three intervention groups after stratification by year of graduation . One third of the participating physicians were forwarded written information about the indications and limitations of benzodiazepines , another third received both written and oral information , and the remaining third ( the control group ) obtained no information at all . A comparison of the number of benzodiazepines prescribed per 100 patient contacts with prescription before and after the intervention showed an average decrease of 3 % in the control group , of 14 % in physicians who received only written information , and of 24 % in physicians who were given additional oral information . Post hoc pairwise comparisons revealed a significant difference at the 1 % level in the number of benzodiazepines prescribed between physicians who received both written and oral information and the control group . A follow-up survey conducted 4 weeks after the intervention showed that the oral information campaign positively affected physicians ' attitudes about the value of oral drug information from an industry-independent source OBJECTIVE To evaluate the impact of regular multidisciplinary team interventions on the quantity and quality of psychotropic drug prescribing in Swedish nursing homes . DESIGN A r and omized controlled trial . SETTING A sample of 33 nursing homes : 15 experimental homes and 18 control homes representing 5 % of all Swedish nursing homes . PARTICIPANTS The sample consisted of 1854 long-term care residents with an average age of 83 years . Seventy percent of the residents were women , and 42 % had a documented diagnosis of dementia . An additional 5 % had a psychotic disorder , and 7 % had a diagnosis of depression . INTERVENTION Experimental homes participated in an outreach program that was design ed to influence drug use through improved teamwork among physicians , pharmacists , nurses , and nurses ' assistants . Multidisciplinary team meetings were held on a regular basis throughout the 12-month study period . MEASUREMENTS Lists of each resident 's prescriptions were collected 1 month before and 1 month after the 12-month intervention . Measures included the proportion of residents with any psychotropic drug , polymedicine , and therapeutic duplication and proportion of residents with nonrecommended and acceptable drugs in each psychotropic drug class , as defined by current Swedish guidelines . RESULTS Baseline results show extensive psychotropic drug prescribing , with the most commonly prescribed drugs being hypnotics ( 40 % ) , anxiolytics ( 40 % ) , and antipsychotics ( 38 % ) . After 12 months of team meetings in the experimental homes , there was a significant decrease in the prescribing of psychotics ( -19 % ) , benzodiazepine hypnotics ( -37 % ) , and antidepressants ( -59 % ) . Orders for more acceptable antidepressants also increased in the experimental homes . In the control homes there was increased use of acceptable antidepressants , but there were no significant reductions in other drug classes . CONCLUSIONS There is excessive prescription of psychotropic drugs in Swedish nursing homes . Improved teamwork among caregivers can improve prescribing as defined by clinical guidelines OBJECTIVE The aim was to examine the effect of using a Web-based computer program that provides personalized feedback to migraine patients , on the interactions of patients and providers . Background .-Despite the widespread availability of evidence -based migraine treatment guidelines , patients often do not receive optimal treatment to reduce migraine pain and disability . METHODS To address these quality gaps in migraine care , we developed a Web-based computer program , to be used by migraine patients before doctor visits . The feedback is design ed to prompt patients to ask questions that lead to higher quality of care . This study was conducted to examine the effect of using the program on migraine-specific doctor-patient communications . Patients were r and omized to use the Website before ( intervention ) or after ( control ) a visit with their provider . The outcome measures were the migraine-specific topics discussed during the visit , measured by an exit survey after the visit . RESULTS Fifty of 53 subjects r and omized completed the postvisit measures ( 94 % ) . Overall , the mean age was 42.0 years , most patients were female ( 86.5 % ) , all were white , and 58.5 % saw a headache specialist during their visit . Most ( 75.0 % ) reported having headaches at least once per week and 48.1 % rated their headaches as " severe . " Intervention patients were significantly more likely to " discuss whether you had migraine headaches or some other type of headache ? " ( 89.3 % vs 54.5 % ; P < .01 ) and to " discuss whether or not there may be a more serious cause of your headaches ? " ( 50.0 % vs 13.6 % ; P < .01 ) . Intervention patients were more likely to report discussing 8 of 12 migraine-related topics more frequently and a greater overall number of topics ( 5.5 vs 4.3 ) than control patients . This difference was not statistically significant . CONCLUSIONS These results suggest that the Website may have a positive impact on migraine-specific doctor-patient communications . A larger study , including important quality of life and utilization outcomes , is warranted BACKGROUND It is recommended that long-term users of benzodiazepines in general practice be withdrawn from their medication where possible . AIM A study was undertaken to assess the effectiveness of minimal intervention delivered by general practitioners in helping chronic users of benzodiazepines to withdraw from their medication , and to determine the psychological sequelae on patients of such intervention . METHOD Patients taking benzodiazepines regularly for at least one year were recruited by their general practitioner and allocated either to a group receiving brief advice during one consultation supplemented by a self-help booklet or to a control group who received routine care . The patients completed the 12-item general health question naire and a benzodiazepine withdrawal symptom question naire at the outset of the study and at three and six months after this . RESULTS Eighteen per cent of patients in the intervention group ( 9/50 ) had a reduction in benzodiazepine prescribing recorded in the notes compared with 5 % of the 55 patients in the control group ( P < 0.05 ) . In the intervention group , 63 % of patients had a score of two or more on the general health question naire at baseline compared with 52 % at six months . Of the 20 intervention patients reporting benzodiazepine reduction , 60 % had a score of two or more at baseline compared with 40 % at six months . Intervention patients had significantly more qualitative , but not quantitative , withdrawal symptoms at six months compared with baseline . Consultation rates were not increased in the intervention group . CONCLUSION The study indicates that some chronic users can successfully reduce their intake of benzodiazepines with simple advice from the general practitioner and a self-help booklet . This type of intervention does not lead to psychological distress or increased consultation OBJECTIVES Drug use review is used by both the public and private sector to influence prescribing behavior and patient drug use . Past interventions mailed to prescribers have had mixed results . The objective was to evaluate the effect of a one-time , mailed intervention on subsequent use of sedative hypnotic medication . METHODS An experimental design was used . The intervention contained guidelines for the use of sedative hypnotics , a prescriber profile detailing sedative hypnotic prescribing , and a patient profile . Clustering of patients and their shared prescribers was done to avoid contamination bias and statistical problems associated with a lack of independence of observations . Subjects were 189 Washington State Medicaid recipients who had received at least one tablet per day of a sedative hypnotic medication for 1 year and their prescribing physicians or ( when information about the physician was lacking ) the dispensing pharmacy . RESULTS A significant reduction in the use of targeted sedative hypnotic medications was measured in the intervention group ( -27.6 % ) versus the control group ( -8.5 % ) . In the intervention group , 9.4 % of patients began a new prescription for a benzodiazepine not targeted by the drug use review , whereas no control patients had new use of nontarget benzodiazepines . CONCLUSIONS The intervention achieved a statistically significant decrease in targeted drug use , and the amount of reduction is likely to have decreased the risk of fractures associated with benzodiazepine use . This study adds to the recent evidence that mailed drug use review interventions can have a desirable impact on patient drug use OBJECTIVES To examine the effect of replacing drug-specific computerized prescribing alerts with age-specific alerts on rates of dispensing potentially inappropriate medications in older people and to determine whether group academic detailing enhances the effectiveness of these alerts . DESIGN Cluster-r and omized trial of group academic detailing and interrupted time-series analysis . SETTING Fifteen clinics of a staff-model health maintenance organization . PARTICIPANTS Seven practice s ( 113 clinicians , 24,119 patients ) were r and omly assigned to receive age-specific prescribing alerts plus the academic detailing intervention ; eight practice s ( 126 clinicians , 26,805 patients ) received alerts alone . Prior implementation of drug-specific alerts established a downward trend in use of target medications that served as the baseline trend for the present study . INTERVENTION The computerized age-specific alerts occurred at the time of prescribing a targeted potentially inappropriate medication ( e.g. , tertiary tricyclic amine antidepressants , long-acting benzodiazepines , propoxyphene ) and suggested an alternative medication . Clinicians at seven sites were r and omized to group academic detailing , an interactive educational program delivering evidence -based information . MEASUREMENTS Number of target medications dispensed per 10,000 patients per quarter , 2 years before and 1.5 years after the replacement of drug-specific with age-specific alerts . RESULTS Age-specific alerts result ed in a continuation of the effects of the drug-specific alerts without measurable additional effect ( P=.75 for level change ) , but the age-specific alerts led to fewer false-positive alerts for clinicians . Group academic detailing did not enhance the effect of the alerts . CONCLUSION Age-specific alerts sustained the effectiveness of drug-specific alerts to reduce potentially inappropriate prescribing in older people and result ed in a considerably decreased burden of the alerts OBJECTIVE To determine the effectiveness of different types of interventions in improving health professional performance and health outcomes . DATA SOURCES MEDLINE , SCI SEARCH , CINAHL and the Research and Development Re source Base in CME were search ed for trials of educational interventions in the health care professions published between 1970 and 1993 inclusive . STUDY SELECTION Studies were selected if they provided objective measurements of health professional performance or health outcomes and employed r and om or quasi-r and om allocation methods in their study design s to assign individual subjects or groups . Interventions included such activities as conferences , outreach visits , the use of local opinion leaders , audit and feedback , and reminder systems . DATA EXTRACTION Details extracted from the studies included the study design ; the unit of allocation ( e.g. , patient , provider , practice , hospital ) ; the characteristics of the targeted health care professionals , educational interventions and patients ( when appropriate ) ; and the main outcome measure . DATA SYNTHESIS The inclusion criteria were met by 102 trials . Areas of behaviour change included general patient management , preventive services , prescribing practice s , treatment of specific conditions such as hypertension or diabetes , and diagnostic service or hospital utilization . Dissemination-only strategies , such as conferences or the mailing of unsolicited material s , demonstrated little or no changes in health professional behaviour or health outcome when used alone . More complex interventions , such as the use of outreach visits or local opinion leaders , ranged from ineffective to highly effective but were most often moderately effective ( result ing in reductions of 20 % to 50 % in the incidence of inappropriate performance ) . CONCLUSION There are no " magic bullets " for improving the quality of health care , but there are a wide range of interventions available that , if used appropriately , could lead to important improvements in professional practice and patient outcomes |
10,389 | 16,413,876 | INTERPRETATION We saw no evidence that liquid-based cytology reduced the proportion of unsatisfactory slides , or detected more high- grade lesions in high- quality studies , than conventional cytology .
This review does not lend support to cl aims of better performance by liquid-based cytology . | BACKGROUND Liquid-based cytology is reported to increase the sensitivity of cervical cytology and the proportion of slides that are satisfactory for assessment , in comparison with conventional cytology .
Although some countries have changed to liquid-based cytology for cervical screening , controversy remains .
We review ed the published work to assess the performance of liquid-based cytology relative to conventional cytology in primary studies assessed to be of low , medium , or high method ological quality . | This study was conducted to compare the diagnoses and specimen adequacy of the ThinPrep ( Cytyc Corporation , Boxborough , MA , USA ) and conventional Papanicolaou preparation methods for cervical cytology . Cervical specimens from 972 patients from our gynecology clinic were analyzed . A single sample of the uterine cervix taken from each patient was first used to prepare the conventional Papanicolaou smear . Afterward , the residual tissue on the sampling device was rinsed into a fluid preservative from which two slides were prepared by means of the ThinPrep method . Conventional and ThinPrep slides were examined independently . Cytologic diagnoses and specimen adequacy were classified according to the Bethesda System . The diagnoses based on the ThinPrep and conventional smears matched in 939 ( 96.6 % ) cases . Low- grade squamous epithelial or higher grade lesions were detected with at least one of the methods in 59 cases and with both methods in 42 cases . Fifteen more cases of low- grade squamous epithelial or higher grade lesions ( 58 vs 43 ; p < 0.001 ) and 10 more cases of high- grade squamous epithelial lesions or carcinoma ( 42 vs 32 ; p = 0.006 ) , were detected with ThinPrep than with conventional smears . The ThinPrep method yielded a higher rate of specimens that were satisfactory for cytologic examination than the conventional smears ( 89.8 % vs 70.9 % , p < 0.001 ) . The detection rate of infectious agents was also higher with the ThinPrep method ( 14.9 % vs 6.6 % ; p < 0.001 ) . The reproducibility rate of the twin slides prepared with the ThinPrep method was greater than 99 % . In conclusion , the ThinPrep method yielded a significantly higher positive detection rate of cervical abnormalities and more satisfactory specimens than conventional Papanicolaou smears The authors compared the accuracy of conventionally prepared smears and smears prepared by an automated , fluid-based , thin-layer processing device in the detection of cytologic abnormalities . A total of 3218 patients from five centers took part in this study , in which a single cervical sample was split into a matched pair . The conventional smear was made in the routine fashion ; the remainder of the cells on the sampling device were rinsed into a transport-fixation fluid . A slide was then prepared from the solution using the thin-layer processor . Diagnostic findings identified on the two preparations were compared in a blinded fashion , and a discrepancy resolution procedure was used to eliminate screening differences . Overall , there was a high correlation in the diagnoses of the two methods . For low- grade or more severe disease , the thin-layer method result ed in a 13 % increase in the rate of detection , as compared with the conventional Papanicolaou smear technique OBJECTIVE To obtain preliminary data on the Roche CytoRich thin-layer system for the preparation of gynecologic cytology specimens , derived from a pre clinical startup evaluation of the instrument and comparing the CytoRich method to conventional smears . STUDY DESIGN At six different clinical sites , 286 pairs of conventional and CytoRich slides derived from the same patient sample were compared for the following : final Bethesda classification diagnosis , specimen adequacy and presence of microorganisms . RESULTS The study showed agreement between the methods for an exact Bethesda diagnosis in 78 % and agreement within one Bethesda diagnosis category in 95 % . The CytoRich method diagnosed more cases of squamous intraepithelial lesion ( SIL ) than did the conventional method , and the differences in SIL detection were statistically significant . The CytoRich method identified similar numbers of cases with microorganisms as did the conventional smears , and the CytoRich system improved overall specimen adequacy as compared to the conventional method , with fewer cases of unsatisfactory and less-than-optimal smears . CONCLUSION The CytoRich method may improve the overall sensitivity and specificity of the cervical cytology procedure . Clinical trials to verify these preliminary data are ongoing OBJECTIVE To examine the efficacy of the ThinPrep method , an automated , fluid-based technique for the collection and preparation of exfoliated and aspirated cells in cervical cytology . STUDY DESIGN A total of 251 patients participated . From each patient a sample was obtained by scraping with a wooden spatula , split and prepared with both conventional Papanicolaou and ThinPrep methods . In the ThinPrep processor , epithelial cells were homogenized in a vial of preservative solution and r and omly sample d onto a microscopic slide . From a single vial of sample suspension a series of 10 ThinPrep slides of the same quality were made . All cells were concentrated within an approximately 20-mm-diameter circle in a uniform , thin layer on the ThinPrep slide . RESULTS Twenty-five percent of the screening area , 10 % of the epithelial cells observed and 50 % of the screening time were required to arrive at a final diagnosis as compared with the Papanicolaou smear . Virtually complete concurrence was ascertained between the Papanicolaou and ThinPrep diagnoses , for direct agreement of 95.3 % and agreement within one diagnostic grade of 99.5 % . CONCLUSION An overall improvement was ascertained in the preparation of microscopic slides and the recognition of abnormal cells with the ThinPrep method OBJECTIVE To compare the cytologic diagnoses and specimen adequacy of the ThinPrep Pap Test with historical data within a distinct patient population to assess test performance and its impact on clinical practice . STUDY DESIGN A total of 16,314 ThinPrep Pap tests were processed and evaluated at Fletcher Allen Health Care over a seven-month period . A subset of 8,574 tests from a selected provider group ( cohort ) was compared to the historical conventional cervical cytologic smear data from the cohort population for both cytologic diagnoses and specimen adequacy . The cohort consisted of 12 practice groups , including 60 physicians and providers , utilizing the ThinPrep Pap Test as their primary cervical cancer screening sampling technique . Cytologic diagnoses and specimen adequacy were classified using the Bethesda system . RESULTS Using a three-tiered diagnostic system similar to the Cytyc clinical trials ( within normal limits [ WNL ] , atypical squamous cells of undetermined significance [ASCUS]/atypical gl and ular cells of undetermined significance [ AGUS ] and low grade squamous intraepithelial lesion and higher [LSIL]+ ) , the ThinPrep method increased the percentage of cases that could be definitively diagnosed as WNL by 1.71 % , lowered the percentage of ambiguous or borderline cases diagnosed as ASCUS/AGUS by 26.59 % and increased the percentage of cases diagnostic of LSIL+ by 52.15 % in the cohort population . Further subdivision by the Bethesda classification showed that the identification of infectious agents increased 25.51 % and the detection of high grade squamous intraepithelial lesion/carcinoma increased 55.14 % . Concurrently , cases reported as benign cellular changes ( reactive/reparative ) decreased 23.1 % , and the percentage of cases reported as unsatisfactory/"limited by ... " was reduced 52.71 % . Histologic correlation of cases reported as squamous intraepithelial lesion revealed that the percentage of patients with subsequent benign biopsies was reduced by 31.7 % utilizing the ThinPrep technique . Further , the percentage of ThinPrep patients with histologically confirmed cervical intraepithelial neoplasia ( CIN ) 1 and CIN 2/3 increased by 16.3 % and 9.3 % , respectively . CONCLUSION Implementation of the ThinPrep Pap Test result ed in statistically significant improvements in both diagnostic yield and specimen adequacy , as seen by others in clinical trials . Comparison of results to historical data within a cohort population reinforced earlier data and lent further support to the cl aim that the ThinPrep Pap Test is " significantly more effective " than the conventional smear in clinical practice OBJECTIVE To compare the CytoRich system with conventional cervical cytology in a university medical center hospital laboratory . STUDY DESIGN The CytoRich system combines liquid preservation , selective reduction of blood/inflammation , thin-layer preparation and discrete staining . Two thous and thirty-two parallel conventional and CytoRich sample s were examined as part of a multicenter trial of the CytoRich/AutoCyte systems . Same-patient conventional and CytoRich slides were su bmi tted to separate cytotechnologists blindly . The results were compared , and all nonmatching sample pairs were review ed again . A consensus diagnosis was derived for all cases . The initial readings of the CytoRich and conventional smears were compared with each other and with the consensus diagnosis . RESULTS Of the 148 squamous intraepithelial lesions ( SILs ) found by either method , 85 % were found by CytoRich , while only 58.5 % were found by conventional smear . As compared with the consensus diagnosis , CytoRich slides had 86.7 % sensitivity for SIL and 99.1 % specificity , while the conventional slides had 63.6 % sensitivity and 99.7 % specificity . Consensus review result ed in upgrading to SIL in 1.8 % of conventional slides and 1.4 % of CytoRich slides . The biopsy correlation results were similar for the two methods . CONCLUSION The CytoRich system affords excellent cellular presentations and superior sensitivity for SILs when compared to the conventional technique OBJECTIVE To compare the accuracy of thin-layer cytology with Autocyte PREP ( TriPath Imaging Inc. , Burlington , North Carolina , U.S.A. ) with conventional smears in 500 women undergoing cervical cone biopsy . STUDY DESIGN The study was performed among 500 consecutive women presenting for cone biopsy for high grade cervical intraepithelial neoplasia ( CIN ) on biopsy in 350 ( 70 % ) and discrepant cytology/colpohistology in 150 ( 30 % ) . Before performing a cone biopsy , two cervical sample s were collected for conventional smears and thin-layer cytologic slides , with r and omization of the order . Conventional smears were stained and diagnosed at Pasteur Cerba , while thin-layer cytologic slides were processed at a local TriPath office ( Meylan , France ) and sent in a masked fashion for screening at Pasteur Cerba . Any slides initially read as normal were review ed again and reported without knowledge of the other cytologic or cone biopsy data . The final cytologic diagnoses for the two methods were compared with histopathology of the cone biopsy . RESULTS The conventional smear was unsatisfactory in 58 ( 11.6 % ) of cases , while there were 4 ( 0.8 % ) unsatisfactory thin-layer cytologic slides ( P < .001 ) . Endocervical cells were missing from 31 ( 6.2 % ) of conventional smears and 34 ( 6.8 % ) of thin-layer cytologic slides . For the pooled data , sensitivities of conventional smear and thin layer for detecting high grade CIN ( 0.82 % and 0.86 % , respectively ) were similar as were specificities ( 0.40 % and 0.43 % , respectively ) . When first sample s were compared , the sensitivities of the conventional smear and thin layer for high grade CIN were 0.79 % and 0.89 % , respectively ( P = .02 ) , with corresponding specificities of 0.41 % and 0.36 % ( P < .01 ) . CONCLUSION When controlled for sample order , the sensitivity of thin-layer cytology for detecting high grade CIN was significantly higher than that of conventional smears in patients with previous abnormal cytology , but at the expense of specificity OBJECTIVE To compare ThinPrep ( TP ) Papanicolaou smears ( Cytyc Corp. , Box-borough , Massachusetts , U.S.A. ) with matching conventional Papanicolaou ( CP ) smears for specimen adequacy , cytologic quality , diagnostic accuracy and screening time . STUDY DESIGN In this prospect i ve study of 1,024 women a split- sample , matched-pair design in favor of CP slides based on single-blind criteria was followed with a smear on a glass slide for CP and the remaining material collected in Preserv-Cyt solution ( Cytyc ) for a TP smear . A Cytobrush ( Medsc and , Hollywood , Florida , U.S.A. ) was used for smear preparation for CP . TP smears were processed in ThinPrep 2000 ( Cytyc ) . Smears were stained with Papanicolaou stain and were interpreted according to the Bethesda system . RESULTS The number of satisfactory but limited ( SBL ) cases with TP were 77 ( 7.5 % ) as compared to 127 ( 12.4 % ) with the CP method . This reduction in SBL smears with the TP method and consequent increase in satisfactory smears were highly significant ( P < .001 ) by McNemar 's test . As regards unsatisfactory smears in discordant pairs , although the number of unsatisfactory smears was higher with TP ( 41 cases ) as against CP ( 27 cases ) , the difference was not statistically significant ( P < .05 ) . The split- sample method showed a high correlation between the CP and TP diagnoses . TP smears had a significant advantage over CP smears in the reduction in the number of ASCUS and AGUS cases ( 14 vs. 29 ) ( P < .05 ) and increased the pickup rate of LSIL , 6 vs. 1 . Time taken to screen the TP smears was half that of CP smears . No cases of LSIL or HSIL were missed on TP smears . CONCLUSION The liquid-based processor significantly improved the adequacy and quality of smears , result ing in fewer recall cases for SBL smears , leading to more definitive diagnoses in atypical cases , increasing the pickup rate of LSILs and reducing the screening time . A machine h and ling multiple specimens automatically would decrease cost and be an asset to a cytopathology laboratory OBJECTIVE To compare the sensitivity , specificity and specimen adequacy of the ThinPrep Pap Test ( TP ) with the conventional Pap Test ( CV ) in a low-risk population with subsequent follow-up of HSIL cases . STUDY DESIGN A prospect i ve , r and omized , controlled design was chosen to compare the TP with CV . Cytologic diagnosis and specimen adequacy were evaluated and compared with histology data in high grade squamous intraepithelial lesion ( HSIL ) cases . Fifteen gynecologists in private practice , all trained in colposcopy , participated in the trial . Cytologic diagnosis , specimen adequacy and follow-up of the cytologic HSIL cases were compared in the two groups . In total , 1,999 patients were included , 997 in the TP group and 1,002 in the CV group . R and omization assignments were design ated on cytology case report forms , which were placed in sealed envelopes . Each envelope had a sequential r and omization number on the outside to allow tracking and authentication of r and omization assignments . RESULTS Comparison of results between CVs and TPs revealed no statistically significant differences in all diagnostic categories , ranging from " within normal limits " to HSIL . Specimen adequacy , however , was superior with CVs ( P < .001 ) . The cytologic diagnosis of HSIL correlated with the histologic diagnosis in 91 % of the TP group and 100 % of the CV group . CONCLUSION Because there was no statistically significant difference in sensitivity and specificity of the two techniques , improved detection of cervical abnormalities and better specimen adequacy might not be a consequence of utilizing liquid-based preparations but of a better sampling technique . Removing mucus and cellular debris from the cervical surface with a cellulose swab before sampling cells with a proper sampling device results in the same sensitivity and specimen adequacy and is much less expensive than the liquid-based technique With current constraints on health care re sources and emphasis on value for money , new diagnostic imaging technologies must be assessed and their value demonstrated . The state of the art in the field of diagnostic imaging technology assessment advocates a hierarchical step-by-step approach . Although rigorous , such a hierarchical assessment is time-consuming , and , given the current rapid advances in technology , results are often too late to influence management and policy decisions . The purpose of this article is to discuss a study design in which development , assessment , and implementation of new diagnostic imaging technology take place concurrently in one integrated process . An empirically based pragmatic study design is proposed for imaging technology assessment . To minimize bias and enable comparison with current technology , a r and omized controlled design is used whenever feasible and ethical . Outcome measures should reflect the clinical decision-making process based on imaging information and acceptance of the new test . Outcome measures can include additional imaging studies requested , costs of diagnostic work-up and treatment , physicians ' confidence in therapeutic decision making , recruitment rate , and patient outcome measures related to the clinical problem . The key feature of the proposed study design is analysis of trends in outcome measures over time OBJECTIVE : To evaluate the liquid-based ThinPrep Papanicolaou test . DESIGN : Prospect i ve comparison of the ThinPrep test with the conventional Papanicolaou test . SETTING : Cervical smear specimens sent to a private practice , Hong Kong . PATIENTS : A total of 16,541 ThinPrep test specimens and 7258 conventional Papanicolaou smears from Hong Kong women who had been screened for cervical cancer between mid-July 1998 and mid-January 1999 . MAIN OUTCOME MEASURES : Specimen adequacy , endocervical cell content , epithelial cell abnormalities , and micro-organisms present in both types of cervical smears ; histological diagnosis of cervical biopsy specimens of women who had the ThinPrep test . RESULTS : Compared with the conventional Papanicolaou smear test , the ThinPrep test showed a reduction in the frequency of ' unsatisfactory ' ( 0.56 % versus 1.36 % ; P<0.01 ) , ' satisfactory but limited ' ( 1.67 % versus 15.87 % ; P<0.01 ) , and ' atypical squamous cells of undetermined significance ' reports ( 1.72 % versus 3.64 % ; P<0.01 ) . The ThinPrep test was also more effective at detecting squamous intraepithelial lesions , showing a 58 % increase for low- grade lesions ( 2.66 % versus 1.68 % ; P<0.01 ) and 28 % increase for high- grade lesions ( 1.71 % versus 1.34 % ; P<0.01 ) . The sensitivity and positive predictive value of the ThinPrep system were 97.5 % and 94.2 % , respectively . The liquid-based method yielded a higher percentage of sample s that contained endocervical cells compared with conventional smear specimens ( 70.57 % versus 51.23 % ; P<0.001 ) . CONCLUSIONS : The ThinPrep test has a high sensitivity and positive predictive value . The ThinPrep test gives higher- quality specimens and has a higher detection rate of squamous intraepithelial lesions than the conventional Papanicolaou smear test . The drawbacks of the liquid-based system , however , pertain to cost and the additional procedures and training needed The aim of this six-centre , split- sample study was to compare ThinPrep fluid-based cytology to the conventional Papanicolaou smear . Six cytopathology laboratories and 35 gynaecologists participated . 5428 patients met the inclusion criteria ( age > 18 years old , intact cervix , informed consent ) . Each cervical sample was used first to prepare a conventional Pap smear , then the sampling device was rinsed into a PreservCyt vial , and a ThinPrep slide was made . Screening of slide pairs was blinded ( n = 5428 ) . All non-negative concordant cases ( n = 101 ) , all non-concordant cases ( n = 206 ) , and a 5 % r and om sample of concordant negative cases ( n = 272 ) underwent review by one independent pathologist then by the panel of 6 investigators . Initial ( blinded ) screening results for ThinPrep and conventional smears were correlated . Initial diagnoses were correlated with consensus cytological diagnoses . Differences in disease detection were evaluated using McNemar ’s test . On initial screening , 29 % more ASCUS cases and 39 % more low- grade squamous intraepithelial lesions ( LSIL ) and more severe lesions ( LSIL+ ) were detected on the ThinPrep slides than on the conventional smears ( P = 0.001 ) , including 50 % more LSIL and 18 % more high- grade SIL ( HSIL ) . The ASCUS : SIL ratio was lower for the ThinPrep method ( 115:132 = 0.87:1 ) than for the conventional smear method ( 89:94 = 0.95:1 ) . The same trend was observed for the ASCUS/AGUS : LSIL ratio . Independent and consensus review confirmed 145 LSIL+ diagnoses ; of these , 18 % more had been detected initially on the ThinPrep slides than on the conventional smears ( P = 0.041 ) . The ThinPrep Pap Test is more accurate than the conventional Pap test and has the potential to optimize the effectiveness of primary cervical cancer screening . © 2001 Cancer Research Campaign Objective To compare the cytologic diagnoses and specimen adequacy of a fluid-based , thin-layer preparation and conventional Papanicolaou tests . Methods A total of 7360 women from six separate sites — three screening centers and three hospitals — participated in split- sample /matched-pair , double-masked clinical trials . A conventional Papanicolaou test was performed , after which residual material on the sampling device was rinsed into a fluid preservative from which a thin-layer slide ( ThinPrep ) was prepared using the ThinPrep 2000 automated slide processor ( Cytyc Corp. , Boxborough , MA ) . Conventional and ThinPrep slides were read independently . Cytologic diagnoses and specimen adequacy were classified using the Bethesda system . Results For the three screening centers , 65 % more diagnoses of low- grade squamous intraepithelial lesions and higher were made on the ThinPrep slides ( P < .001 ) ; for the three hospital centers , 6 % more of these diagnoses were made with the ThinPrep method ( P = .294 ) . Comparison of specimen adequacy showed a significant increase in satisfactory specimens and a reduction in the number of “ satisfactory but limited by ” specimens using the ThinPrep method ( P < .001 ) . Conclusion The fluid-based , ThinPrep method of sample preparation result ed in a statistically significant increase in cytologic diagnosis of cervical cancer precursors and in specimen adequacy compared with the conventional Papanicolaou testing method To evaluate the sensitivity and suitability of ThinPrep , a new slide preparation technique , 2026 paired cervical cytology slides were examined . After conventional Papanicolaou smears were prepared , the sampling instruments were rinsed in a fluid fixative . ThinPrep slides were then prepared in the laboratory from the surplus cells in the fixative . Compared with the Pap smears , ThinPrep slides were easier and quicker to screen , were inconclusive less often , and had similar rates for detecting abnormalities and infection . There were more unsatisfactory ThinPrep slides and more ThinPrep slides lacked endocervical cells . Both of these shortcomings were found to be linked to the choice of sampling implements . This study , in which a variety of sampling instruments was used , fails to confirm some of the previous cl aims made for the new technique Thin-layer ( TL ) technology can improve the detection rate for squamous lesions of the uterine cervix . Studies to date have under-represented high grade lesions and malignancies . The present study utilized a patient population at high risk for such lesions in order to analyze the performance of TL procedures in this group , and in addition , to assess the similarities and differences in morphologic appearances of specimens prepared by the two methods . Conventional ( CS ) and thin-layer smears ( TLS ) were made in parallel from the same specimen . Each slide was examined in a blinded fashion . Diagnoses were compared and morphologic observations made . Two hundred fifty-nine cases were included , of which 32 ( 12 % ) were high grade dysplasias ( 11 ) or carcinomas ( 21 ) . Thirty five ( 14 % ) were atypical or low grade dysplasias . There was exact correlation between Bethesda classification in 231 cases ( 89 % ) . Of the 21 carcinomas identified , 19 ( 91 % ) were present on each preparation . Two cases of endometrial adenocarcinoma were missed on unsatisfactory or negative TLS . One case of squamous cell carcinoma was called high grade squamous intraepithelial lesion ( HGSIL ) on TLS while the CS was unsatisfactory . Three cases called atypical gl and ular cells ( AGCUS ) on TLS , and negative on CS , showed HGSIL ( 1 ) or no lesion ( 2 ) on follow-up . Morphologic features of low grade lesions were virtually identical on both preparations . Distinct features were noted on TLS in the high grade lesions . These included smaller appearing nuclear areas , less distinct nuclear chromatin , thicker three-dimensional groupings , and more isolated cells . Such findings were most pronounced in the gl and ular lesions . With training and experience , these features were easily identified in TL preparations , further documenting the utility of this procedure for use in routine practice The diagnoses of 1,000 pairs of conventional Papanicolaou ( Pap ) smears and ThinPrep preparations were compared . Cervical cells were collected using an Ayre spatula and endocervical brush . The conventional smear was made first , the collection devices were rinsed into PreservCyt solution , and the slides were prepared using the ThinPrep Processor . The diagnoses of the paired smears agreed in 988 of the 1,000 cases ( 98.8 % ) , including 949 negatives , 28 atypicals , 9 low grade squamous intraepithelial lesions ( LGSIL ) , and 2 high grade squamous intraepithelial lesions ( HGSIL ) . Five cases where LGSIL or HGSIL was found on the ThinPrep slide were negative or atypical on the conventional smear . No conventional smear abnormalities were missed on the ThinPrep slide . Although not statistically significant , this difference indicates that the ThinPrep method gives a better diagnosis of abnormalities than the conventional method . The ThinPrep method was acceptable to participating physicians and ThinPreps were easier and faster to screen than conventional smears OBJECTIVE To further evaluate the effectiveness of the AutoCyte PREP thin-layer slide preparation ( TriPath Imaging , Inc. , Burlington , North Carolina ) as compared to conventional Pap smears . STUDY DESIGN A split- sample , blinded evaluation of matched thin-layer preparations and conventional smears from 2,438 patients was performed . This material was enriched by including 260 cases of high grade squamous intraepithelial lesions ( HSILs ) and cancer cases from an earlier study . Many of these cases were difficult to diagnose , containing very few abnormal cells on one or both matching slides . The preparations were evaluated multiple times by both thin-layer-inexperienced and -experienced cytology professionals to better compare performance related to preparation quality alone . RESULTS The initial evaluations of the slides by personnel with only brief training in thin-layer interpretation demonstrated equivalent performance for the two preparations . The reevaluation study by cytology professionals with several months of thin-layer experience demonstrated a statistically significant improvement in detection of both LSIL and HSIL lesions using AutoCyte PREP slides . There was also a statistically significant improvement in the number of satisfactory sample s using the AutoCyte PREP method . CONCLUSION The study demonstrated that the AutoCyte PREP thin-layer slide preparation is at least equivalent to conventional Pap smears in the detection of LSIL and HSIL , even when evaluated by cytology professionals who have been newly trained in the thin-layer method and that , with increased experience , the thin-layer AutoCyte PREP slide preparation method showed a statistically significant improvement in disease detection OBJECTIVE This study was undertaken to compare alternative strategies for the initial management of a cytologic diagnosis of atypical squamous cells of undetermined significance ( ASCUS ) . STUDY DESIGN A total of 3488 women with a community-based ASCUS interpretation were r and omly assigned to immediate colposcopy , triage that was based on enrollment HPV DNA testing and liquid-based cytology at a colposcopy referral threshold of high- grade squamous intraepithelial lesion ( HSIL ) , or conservative management based on repeat cytology at a referral threshold of HSIL . All arms included 2 years of semiannual follow-up and colposcopy at exit . Loop electrosurgical excision procedure was offered to women with histologic diagnoses of cervical intraepithelial neoplasia ( CIN ) grade 2 or 3 at any visit or persistent CIN grade 1 at exit . The study end point was 2-year cumulative diagnosis of CIN grade 3 . RESULTS The 2-year cumulative diagnosis of CIN grade 3 was 8 % to 9 % in all study arms . The immediate colposcopy strategy yielded 53.6 % sensitivity for cumulative cases of CIN grade 3 diagnosed over 2 years . The human papillomavirus ( HPV ) triage strategy referred 55.6 % of women and detected 72.3 % of cumulative cases of CIN grade 3 . A conservative management strategy of repeat cytology at the HSIL threshold referred 12.3 % of women while detecting 54.6 % of cumulative CIN grade 3 . To compare triage tests , we re-estimated the performance of HPV and cytology in successfully referring women with underlying CIN grade 3 ( ie , ignoring the insensitivity we discovered in colposcopically directed biopsies ) . A single enrollment HPV test identified 92.4 % of the women diagnosed with CIN grade 3 . Serial cytology , even at an ASCUS threshold , would have required two visits to achieve similar sensitivity ( 95.4 % ) and would have referred 67.1 % to colposcopy . CONCLUSION HPV triage is at least as sensitive as immediate colposcopy for detecting CIN grade 3 and refers about half as many women to colposcopy . Follow-up that used repeat cytology is sensitive at an ASCUS referral threshold but requires two follow-up visits and ultimately more colposcopic examinations than HPV triage The objective of this study was to compare the sensitivity of a new test method with the smear method for detection of neoplasia of the uterine cervix . The new procedure , the ThinPrep process , is an automated , fluid-based technique for the collection and preparation of exfoliated and aspirated cytologic specimens . A single sample from each patient was split and prepared both with the smear and test methods . The diagnostic results from the two slides were compared in this blind study . Among a total of 2,655 patients , diagnoses concurred in 92 % of cases and were within one diagnostic level of each other 98 % of the time . The ThinPrep method facilitated the detection of more low- grade lesions ( P less than .001 , McNemar 's test ) . In addition , the test method decreased the number of ambiguous interpretations . The ThinPrep method appears to improve the cervical cytologic smear quality by the harvest of a r and om and reproducible sample , with a reduction in artifacts . The new method improves the sensitivity of the cervical cytologic screening test OBJECTIVE To evaluate the ThinPrep Pap test as an adjunct to the conventional Pap smear . DESIGN AND SETTING Prospect ively collected cervical sample s were split for independent screening at a large specialised private gynaecological pathology practice in Sydney . MAIN OUTCOME MEASURES Detection of additional significant abnormalities ( cervical intraepithelial neoplasia 1 , or more severe ) ; changed management recommendations from " repeat smear in 12 months " or " ... six months " to " colposcopy " , a reduction in unsatisfactory reports . RESULTS 35,560 paired ( split- sample ) conventional and ThinPrep slides were prepared . Significant abnormalities were detected in 724 conventional smears ( 2 % ) . Additional significant abnormalities were found in 85 ThinPrep slides whose corresponding conventional smear was negative or unsatisfactory even after review , representing a 12 % increase in the detection of significant abnormalities . As a result of the addition of ThinPrep , management recommendations were changed from " repeat smear in 12 months " or " ... six months " to " colposcopy " for 89 of 1669 women whose conventional Pap smears showed minor non-specific changes or papillomavirus . There were 1258 conventional smears ( 3.5 % ) that were unsatisfactory compared with 235 ThinPrep slides ( 0.7 % ) ; for only 74 sample s ( 0.2 % ) were both slides unsatisfactory . CONCLUSIONS The addition of the ThinPrep Pap test improves detection and clinical management of cervical abnormalities , and reduces the number of unsatisfactory sample s which would otherwise require repeat tests OBJECTIVE To compare the quality and sensitivity of CytoRich slides with conventional cytologic smears and to evaluate the benefits of using this technology as an add-on procedure . STUDY DESIGN The study design consisted of non-r and omized , paired cervical sample s. The subjects were 2,125 Sydney women who were routine patients of 13 gynecologists and 8 general practitioners and had cytologic smears taken between January and June 1995 . All smears were taken using the Cervex brush . After preparing the conventional cytologic smear slide , the head of the sample r was detached and placed in a vial of fluid fixative . Paired slides were then prepared in the laboratory from the cells in the fluid fixative , using the CytoRich processing machine . The CytoRich and conventional cytologic smear slides were compared for quality , ease of screening , presence of endocervical cells , recognition of infections , and detection of squamous and gl and ular abnormalities . RESULTS CytoRich slides were of much better quality , were easier to screen , had substantially fewer unsatisfactory results ( 0.3 % vs. 2.6 % ) but lacked endocervical cells more often ( 16.1 % vs. 10.6 % ) . As regards abnormalities , the CytoRich slides showed fewer abnormalities , particularly in the low grade category . However , as a result of screening the paired CytoRich slide , some additional abnormalities were detected and a number of abnormalities reported on the conventional slide were reclassified ( some to higher grade s but more to negative ) . CONCLUSION As an add-on technology , the CytoRich process has much to offer , in particular in the virtual elimination of unsatisfactory smears and in helping to resolve the difficult dichotomy between normal and low grade categories . Examining additional cellular material on a CytoRich slide enhances the sensitivity and accuracy of the combined results The performance of thin-layer cervical cytology with the use of ThinPrep ( Cytyc Corporation , Boxborough , MA ) was assessed by comparing the original independent diagnosis of ThinPrep slides and conventional smears prepared from 1780 split sample s with the most abnormal diagnosis per patient on the basis of an independent pathologist 's masked review and with the detection of cancer-associated types of human papillomavirus ( HPV ) DNA . Cases were selected on the basis of the original diagnoses to include all discordant pairs ( those diagnosed as atypical squamous cells of undetermined significance or higher grade , n = 1017 ) , all concordant abnormal pairs ( n = 444 ) , and a r and om 5 % of concordant normal pairs ( n = 319 ) . In screening centers , thin-layer cytology detected 135 ( 70.3 % ) of 192 women diagnosed as having squamous epithelial lesions or a higher grade in the independent review , whereas locally read smears detected 91 ( 47.4 % ) of these patients ( P < .001 ) . In hospital-based cytology laboratories , thin-layer cytology detected 308 ( 86.3 % ) of 357 women diagnosed with SILs or a higher grade in the independent review , compared with 283 ( 79.3 % ) diagnosed with smears ( P = .011 ) . Cancer-associated types of HPV DNA were detected in a slightly higher proportion of women with smears diagnosed as SILs than in women with thin-layer cytology diagnosed as SILs , whereas the overall number of HPV-associated SILs diagnosed was higher with thin-layer cytology . These data suggest that the ThinPrep method detects a higher percentage of SILs as defined in a masked , independent review than do concurrently prepared smears and that diagnoses of SILs rendered with ThinPrep correlate with the detection of cancer-associated types of HPV The aim of the study was to assess the ability of the CytoRich System to prepare optimal gynaecological smears for diagnosis . The diagnostic results obtained from evaluating 1,325 matched slide-pairs , prepared using conventional methods and thin-layer technology , were compared . Cytological material for study was obtained using the combined spatula-cytobrush sampling technique . An assessment of the pitfalls associated with the interpretation of these smears was also undertaken . Diagnostic agreement was achieved in 1,272 of the 1,325 matched slide-pairs ( 96.0 % ) , and these included 1,172 negative , 50 atypical , 24 low- grade squamous intraepithelial lesion ( LSIL ) , 24 high- grade SIL ( HSIL ) , and two malignancies . A total of 1,309 cases showed the same diagnosis within one diagnostic grade for an agreement of 98.8 % . Evaluation of the 53 discordant diagnoses revealed that the conventional smear identified a significantly greater number of abnormal smears than the CytoRich technique ( P < .001 ) . It is suspected that the use of the combined spatula-cytobrush sampling technique did not provide adequate residual specimen for CytoRich after conventional smear preparation . This limitation is evidence d by the fact that the CytoRich preparations showed a lower yield of endocervical cells ( P < .001 ) and infectious organisms ( P < .001 ) than was demonstrated on conventional smears . Despite a number of diagnostic pitfalls associated with the interpretation of thin-layer smears , these preparations were easier and faster to screen and showed well-preserved and evenly distributed cells . Thin-layer smears were also characterised by a marked reduction in thick cell groups , air drying artifact , and obscuring inflammation and blood . The results confirm the limitation of the combined spatula-cytobrush technique in these types of comparative studies OBJECTIVE To compare the AutoCyte Prep system ( Burlington , North Carolina ) with conventional cervical cytology in a university medical center laboratory . STUDY DESIGN Split- sample conventional and AutoCyte Preps were examined for 2,156 cases . Same-patient conventional and Prep slides were su bmi tted to separate cytotechnologists blindly . The results were compared on review by a cytopathologist . The Prep slides were subsequently scanned on the AutoCyte Screen automated interactive system , with manual review of the flagged cases . The results were compared with anatomic pathology follow-up when available . RESULTS Of the 158 squamous intraepithelial lesions ( SILs ) found by both methods , 78 % were found by AutoCyte Prep , while 59 % were found by conventional smear ( P < .01 ) . Among the discordant cases , thin-layer slides revealed 88 % more LSIL lesions ( P < .05 ) , a comparable number of high grade SIL lesions and a single case of adenocarcinoma that was ambiguous on the conventional slide . The addition of AutoCyte assisted primary screening demonstrated a net benefit , recovering additional cases referenced as atypical gl and ular cells of undetermined significance and as high grade SIL . CONCLUSION The AutoCyte Prep system affords excellent cellular presentations and superior sensitivity for SILs when compared to the conventional technique . The use of AutoCyte Screen , for primary screening demonstrated performance equivalent to manual screening , with a significant improvement in sensitivity when measured against biopsy results OBJECTIVE To evaluate and compare histologic diagnosis of squamous intraepithelial neoplasia and cancer of the cervix with cytologic diagnosis using the conventional Pap smear versus the AutoCyte PREP liquid-based , thin-layer preparation . STUDY DESIGN Two r and omly selected , large patient groups from the same population were studied using two different cervical cytology preparation techniques . Cytologic results were compared to histologic diagnosis to estimate the relative sensitivities and specificities of the preparations . RESULTS AutoCyte 's liquid-based , thin-layer preparation method demonstrated improved agreement with histologic diagnosis as compared to the conventional Pap smear . This result supported the previously reported finding that use of this thin-layer method reduced atypical squamous cells of undetermined significance cases and substantially increased the detection of squamous intraepithelial lesions ( SILs ) . CONCLUSION Our cytohistologic correlation for conventional Pap smears and the AutoCyte PREP liquid-based preparations demonstrate that the increased rate of both low and high grade SILs on AutoCyte PREP reflects real detection as opposed to overdiagnosis |
10,390 | 24,960,023 | Depot medroxyprogesterone acetate ( DMPA ) was associated with decreased bone mineral density ( BMD ) .
The placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo supplement .
COCs did not appear to negatively affect BMD , and some formulations had more positive effects than others .
Where studies showed differences between groups in bone turnover markers , the results were generally consistent with those for BMD .
For implants , the single-rod etonogestrel group showed a greater BMD decrease versus the two-rod levonorgestrel group but results were not consistent across all implant comparisons .
For example , injectable contraceptives and implants provide effective , long-term birth control yet do not involve a daily regimen . | BACKGROUND Steroidal contraceptive use has been associated with changes in bone mineral density in women .
Whether such changes increase the risk of fractures later in life is not clear .
Osteoporosis is a major public health concern .
Age-related decline in bone mass increases the risk of fracture , especially of the spine , hip , and wrist .
Concern about bone health influences the recommendation and use of these effective contraceptives globally .
OBJECTIVES Our aim was to evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women . | BACKGROUND The aim of the study was to compare bone mineral density ( BMD ) before insertion and at 18 months of use of etonorgestrel- and levonorgestrel-releasing contraceptive implants . METHODS One hundred and eleven women , 19 - 43 years of age , were r and omly allocated to two groups : 56 to etonorgestrel and 55 to levonorgestrel . BMD was evaluated at the midshaft of the ulna and at the distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry before insertion and at 18 months of use . RESULTS There was no difference in baseline demographic or anthropometric characteristics , or in BMD of users of either model of implant . BMD was significantly lower at 18 months of use at the midshaft of the ulna in both groups of users . However , no difference was found at the distal radius . Multiple linear regression analysis showed that the variables associated with BMD at 18 months of use in both implant groups were baseline BMD , body mass index ( BMI ) and difference in BMI ( 0 versus 18 months of use ) . CONCLUSIONS Women of 19 - 43 years of age using either one of the implants showed lower BMD at 18 months of use at the midshaft of the ulna , however , without a difference at the distal radius BACKGROUND This Phase 3 , r and omized , open-label , multicenter study conducted at 44 sites in Europe evaluated the safety and efficacy of a continuous , daily regimen of levonorgestrel ( LNG ) 90 mcg/ethinyl estradiol ( EE ) 20 mcg compared with a 21-day , cyclic LNG 100 mcg/EE 20 mcg regimen . STUDY DESIGN Three hundred twenty-three healthy women were r and omized to continuous LNG 90 mcg/EE 20 mcg and 318 subjects to cyclic LNG 100 mcg/EE 20 mcg for 1 year ( 13 pill packs ) . Pearl index , adverse event ( AE ) incidence and bleeding profiles were assessed . RESULTS No pregnancies occurred with the continuous oral contraceptive ( OC ) ( Pearl index=0.00 ) . As the study progressed , the percentage of women who achieved amenorrhea during each 28-day pill pack increased : 40 % at pill pack 7 , 53 % at pill pack 13 . The percentage of women with no bleeding [ with or without spotting ( defined as not requiring sanitary protection ) ] was 50 % , 69 % and 79 % at pill packs 3 , 7 and 13 , respectively . The incidence of AEs was similar to that of the cyclic OC ( except for metrorrhagia and vaginal bleeding in the first 6 months ) . CONCLUSIONS Continuous LNG 90 mcg/EE 20 mcg was shown to be a safe and effective OC in this direct comparison to a cyclic OC . Suppression of menses and the potential for no bleeding requiring sanitary protection may be provided by this continuous , low-dose OC Background The aim of this study was to evaluate bone mineral density ( BMD ) at baseline and at 18 and 36 months of use of etonogestrel (ENG)- and levonorgestrel (LNG)-releasing contraceptive implants . This is a continuation of a previous study in which BMD was evaluated at baseline and at 18 months of use . Methods A total of 111 women , 19–43 years of age , werer and omly allocated to use one of the two implants . At 36 months of follow-up , only 36 and 39 women were still using the ENG- and LNG-releasing implants , respectively . BMD was evaluated at the distal and at the ultra-distal radius of the non-dominant forearm using dual-energy X-ray absorptiometry . Results There was no difference in the BMD of users of either implant at 18 and at 36 months . BMD was significantly lower at 18 and at 36 months at the distal radius in both groups of users compared to pre-insertion values ; however , no difference was found at the ultra-distal radius . Conclusion Women 19–43 years of age using either one of these two contraceptive implants for 36 months had lower BMD values at the distal radius compared to pre-insertion values ; however , no difference was found at the ultra-distal radius OBJECTIVE The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception . STUDY DESIGN One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned r and omly to receive monthly injections of estradiol cypionate or placebo . The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 ( n = 69 ) to 24 ( n = 36 ) months . Participants , technicians , and physicians were blinded to estrogen treatment . RESULTS Over the 24-month period , the percentage of change from baseline bone mineral density at the lumbar spine was 2.8 % in the estradiol cypionate group versus -1.8 % in the placebo group ( P < .001 ) . At the femoral neck , the percentage of change from baseline bone mineral density was 4.7 % in the estradiol cypionate group versus -5.1 % in the placebo group ( P < .001 ) . CONCLUSION Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections AIM This 12-month study was conducted to evaluate the skeletal effects of two monophasic oral contraceptives containing 20 mug of ethinylestradiol and 100 mug of levonorgestrel ( LEVO ) or 150 mug of desogestrel ( DESO ) . METHODS Fifty-two women ( 18 - 24 years ) were r and omized into the DESO group or the LEVO group ; 36 women served as controls . The areal bone mineral density ( aBMD ) of the femoral neck and the lumbar spine was evaluated by DXA , and parameters of bone geometry and volumetric bone mineral density ( vBMD ) were assessed by peripheral quantitative computed tomography at the distal radius and the tibia . RESULTS The LEVO group did not lose vertebral aBMD , whereas women in the DESO group lost 1.5 % . At the distal radius and the tibia ( shank level , 14 % ) , LEVO induced an increase in total cross-sectional area , indicating increased periosteal bone formation . Radial trabecular vBMD declined by 1.4+/-1.8 % in the DESO group , while it remained unchanged in the LEVO group . CONCLUSION Our study suggests that the skeletal effects of OC preparations may be influenced by progestogenic components in young women BACKGROUND A formulation of depot medroxyprogesterone acetate ( DMPA ) has been developed that allows subcutaneous injection ( 104 mg/0.65 mL ; DMPA-SC ) and achieves highly effective contraception with a similar tolerability profile to intramuscular DMPA ( 150 mg/mL ; DMPA-IM ) . STUDY DESIGN This r and omized , evaluator-blinded study was design ed to compare efficacy , safety , and user satisfaction in women receiving DMPA-SC ( n=266 ) or DMPA-IM ( n=268 ) for 2 years with an option to continue for a third year . The primary objectives were to evaluate bone mineral density ( BMD ) changes and contraceptive efficacy after 2 years . RESULTS A total of 225 women completed the first 2 years of this study ( DMPA-SC , n=116 ; DMPA-IM , n=109 ) . After 2 years of DMPA use , BMD loss was marginally smaller in the DMPA-SC group than in the DMPA-IM group at both the total hip ( -3.3 % and -3.6 % , respectively ) and lumbar spine ( -4.3 % and -5.0 % , respectively ) . In those women who received DMPA during the third year , there were no statistically significant differences in BMD loss between DMPA-SC and DMPA-IM groups at the end of Year 3 . Recovery of BMD was observed in the small sub population of women who had discontinued DMPA-SC or DMPA-IM after the second year . The 2-year treatment-failure cumulative pregnancy rate was 0 % in the DMPA-SC group and 0.8 % ( 95 % confidence interval , 0.00 - 2.37 % ) in the DMPA-IM group ( life-table method ) . Adverse events were similar in the two groups except that injection site reactions were more common in the DMPA-SC group . CONCLUSION DMPA-SC is an effective and well-tolerated contraceptive option , providing comparable efficacy and BMD safety to DMPA-IM BACKGROUND Several studies , including an earlier analysis from the Royal College of General Practitioners ( RCGP ) Oral Contraception Study , have suggested that ever users of oral contraceptives have an increased risk of fracture when compared with never users . In this paper , we examined a subset of women in the RCGP study living in Scotl and to determine whether this risk has persisted . STUDY DESIGN A nested case-control study was carried out using data collected prospect ively for the RCGP Oral Contraception Study . Cases were women with a first ever diagnosis of fracture ( n=651 ) , age-matched to two controls ( n=1302 ) . Adjustments were made for smoking , social class and parity . RESULTS There was not a significant association between ever use of oral contraception and fracture ( adjusted odds ratio 1.05 , 95 % confidence interval 0.86 - 1.29 ) , compared with never users . Neither were significant associations found between fracture and smoking , social class and parity . The findings did not vary material ly with age or type of fracture . CONCLUSION Ever use of oral contraception was not associated with fracture in this study 2 preparations of a sequential oral contraceptive containing 11 tablets of .1 mg mestranol and 10 tablets of .1 mg mestranol and 2 mg chlormadinone were compared : 127 women took the pills with 7 placebos ( Eunomin ) for 848 cycles and 47 women took them without placebos ( GC 527 ) for 267 cycles . 1 pregnancy occurred due to patient error . No differences were recorded in weight changes , bone symptoms , breakthrough bleeding , breast symptoms , or increased libido . Mucorrhea and constipation were more common with the placebos . The side effects of nausea , nervousness , headache , fatigue , and decreased libido were frequent with placebos . 19.8 % discontinued Eunomin , while 23.4 % stopped taking CG 527 . 76.9 % of the women on Eunomin and 65.2 % of those on CG 527 did not have the side effects that they had experienced with previou s pills The question of differential effects on bone density by two different types of progestogen-only methods for contraception in premenopausal women was addressed . Data from a prospect i ve r and omized clinical trial among 22 premenopausal women , age 32.6 ( range 20 - 45 years ) , who were r and omly assigned to either of two treatments with continuous progestogens for contraception were analyzed ; depot-medroxyprogesterone acetate ( DMPA ) or continuous levonorgestrel treatment with subdermal implants ( Norplant ) , respectively . Forearm bone density ( BMDprox ) increased with 2.94 % ( p = 0.006 ) in women who were prescribed levonorgestrel , which was in contrast to stable values in those prescribed depot-medroxy-progesterone acetate ; group difference at 6 months for BMDprox 3.4 % ( 95 % CI 1.3 , 5.5 ; p = 0.025 ) and BMDdist 4.1 % ( 95 % CI - 1.3 , 9.6 ; p = 0.077 ) . The changes in bone density were consistent with the changes in biochemical indices for bone metabolism ; DMPA users showed signs of increased bone turnover and users of levonorgestrel showed increased bone formation with increased levels of both alkaline phosphatase ( p = 0.004 ) and osteocalcin ( p = 0.007 ) . The findings suggest an increase in bone density during treatment with levonorgestrel and stable values during short-term administration of DMPA , in st and ard clinical doses for contraception INTRODUCTION Prior studies have suggested that oral contraceptives ( OCs ) may be associated with an increased fracture risk . However , the previous studies have only performed a limited adjustment for other potential risk factors . SUBJECTS AND METHODS All women with a fracture ( n=64,548 ) in the year 2000 in Denmark served as cases . For each case , three age-matched controls were r and omly drawn from the general population ( n=193,641 ) . Exposure was use of OCs between January 1 , 1996 , and December 31 , 2000 . Adjustments were made for use of other drugs , pregnancy , prior fracture , other diseases and social variables . RESULTS In the unadjusted analysis , use of OCs in low dose was associated with a small increase in overall fracture risk . However , upon adjustment , no increase in fracture risk could be demonstrated in any age or dose group . CONCLUSION Oral contraceptives are not associated with an increase or a decrease in fracture risk . Any change in fracture risk may be due to confounders The aim of the study was to evaluate if a pill containing the same dose of the same type of progestin compound ( gestodene , GES , 75 microg ) but different doses of ethinylestradiol ( EE2 ) ( 20 or 30 microg ) differently influences specific markers of bone resorption ( urinary levels of pyridinoline ( PYR ) and dexoxypyridinoline ( D-PYR ) ) . During the 12 months of the study a significant decrease of urinary levels of PYR and D-PYR was found in 2 groups of young post-adolescent women taking the pills with 20 and 30 microg of EE2 in comparison with control women ( subjects of the same age group with normal menstrual cycle who did not use contraception ) . In women taking pills with 20 or 30 microg EE2 , the levels of sex hormone-binding globulin ( SHBG ) significantly increased during treatment in comparison with baseline , whereas in the same time period no changes occurred in control women . These findings suggest that similar to the pill containing 30 microg EE2 , the lower dosage of the EE2 pill ( 20 microg ) is also capable of reducing bone resorption . Twenty and 30 microg EE2 pills exert the same biological estrogenic effect . In fact , SHBG levels significantly increased with both pills . However , an additional effect of the progestin compound that could act directly on progestin or estrogen receptors of bone can not be excluded . Since contraception with a pill containing the lowest estrogen dose is associated with the lowest incidence of side effects , these findings further suggest a pill containing 20 microg EE2 for young post-adolescent women would be the best choice In this prospect i ve , controlled , r and omized study , we compared the effect of a low-dose 21-day combined oral contraceptive ( COC ) containing 20 microg ethinyl estradiol ( EE ) and 75 microg gestodene ( GTD ) ( Group A ; n = 19 ) with an ultra-low-dose 24-day COC containing 15 microg EE and 60 microg GTD ( Group B ; n = 18 ) on bone turnover and bone mineral density ( BMD ) in young , fertile women . Nineteen healthy fertile women were used as untreated controls ( Group C ) . At 3 , 6 , 9 and 12 months of the study serum osteocalcin ( BGP ) , urinary pyridinoline ( PYD ) and deoxypyridinoline ( D-PYD ) were measured in all subjects . At baseline and after 12 months BMD was determined at lumbar spine by dual-energy X-ray absorptiometry in all patients . In both Groups A and B , urinary levels of PYD and D-PYD at 6 , 9 and 12 months , were significantly reduced in comparison with basal values and with control subjects ( p < 0.05 ) . No significant differences in urinary PYD and D-PYD levels were observed between Groups A and B during the entire period of treatment . At 12 months , no statistically significant difference in spinal BMD values was detected between the three groups and in comparison with basal values . The present study suggests that the two COCs could exert a similar positive effect on bone turnover in young postadolescent women , without any significant and appreciable modification of BMD In this first prospect i ve , double-blind , r and omized , parallel-group study we evaluated the influence of two combined oral contraceptives on bone mineral density ( BMD ) and metabolic bone parameters . One dose-reduced preparation contained 20 microg ethinylestradiol ( EE ) in combination with 100 microg levonorgestrel ( LNG ) ( 20/100 ) was compared with the reference preparation which contained 30 microg EE in combination with 150 microg LNG ( 30/150 ) . Data from 48 volunteers aged 20 - 35 years were obtained over an observation period of 36 treatment cycles . The direction of the change ( increase or decrease ) in all investigated bone-related variables was similar in both treatment groups . As compared to baseline , bone mineral density decreased by 0.4 % in the 20/100 group and by 0.8 % in the 30/150 group after 36 treatment cycles . These changes were not significantly different between the two treatment groups ( p = 0.902 ) . For bone-specific alkaline phosphatase , we measured a mean increase of 55.4 % ( 20/100 group ) and of 113.2 % ( 30/150 group ) after 36 treatment cycles . The two treatments did not differ statistically significantly ( p = 0.522 ) . With respect to cross-linked N-telopeptides ( NTx ) , we detected a decrease of the mean NTx urine concentrations of 21.1 % ( 20/100 ) and of 13.4 % ( 30/150 ) . These changes also did not significantly differ between the two treatments ( p = 0.613 ) . Both study treatments were safe and well-tolerated by all volunteers participating in the study . In conclusion , BMD did not change during the 3-year observation period . Thus , both trial preparations containing either 20 or 30 microg EE in combination with LNG were capable of maintaining BMD in young fertile women . There is no reason to assume that the EE dose reduction had any negative impact on BMD . Because there were no differences in BMD between the treatment groups , it can be assumed that even lower dosages than 20 microg EE might be sufficient for bone protection . Biochemical markers provided evidence for a reduced bone resorption Long-term use of the injectable contraceptive depot medroxyprogesterone acetate ( DMPA , Depo-Provera ) is associated with a reduction in bone mineral density ( BMD ) , particularly in the lumbar spine . The cause of DMPA-associated bone loss is not known , but the relative estrogen deficiency induced by DMPA use could be responsible . We have undertaken a r and omized , double-blind controlled trial of oral estrogen replacement therapy in 38 premenopausal women ( mean age 37 ) with a minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD ( T score < or = 0 ) . Nineteen women were allocated to receive conjugated estrogens ( 0.625 mg/d orally ) and 19 to receive a matching placebo . All continued with regular DMPA injections throughout the study . Areal bone density was measured by dual energy x-ray absorptiometry at the lumbar spine , femoral neck , and total body sites every 6 months for 2 yr ; the main outcome measure being the change in areal BMD at the lumbar spine . At baseline , the two groups were well matched for demographic , anthropometric , and biochemical variables , and for BMD . Twenty-seven subjects completed at least 18 months in the study , and 26 the full 2 yr , with similar numbers dropping out from each group ( mainly for personal reasons ) . In the estrogen-treated group , mean lumbar spine BMD increased 1 % , whereas in the placebo group it fell 2.6 % , over 2 yr . The between group differences were 2.0 % at 12 months ( P = 0.058 ) , 3.2 % at 18 months ( P < 0.01 ) , and 3.5 % at 24 months ( P < 0.002 ) . Differences of lesser statistical magnitude were seen at the femoral neck ( between group differences at 2 yr : 2.7 % , P = 0.24 ) , Ward 's triangle ( 5.0 % , P = 0.055 ) , greater trochanter ( 3.6 % , P = 0.056 ) , total body ( 1.3 % , P = 0.046 ) , legs ( 1.3 % , P = 0.065 ) , and trunk ( 2.0 % , P = 0.029 ) . There were no major adverse events . These data support the view that the likely cause of DMPA-associated bone loss is estrogen deficiency and demonstrate that it can be arrested by estrogen replacement therapy Objective . To compare the effects of a monophasic combined oral contraceptive containing nomegestrol acetate/17β‐estradiol ( NOMAC/E2 ) on bone mineral density with a combined oral contraceptive containing levonorgestrel/ethinylestradiol ( LNG/EE ) . Design . Prospect i ve , r and omized , open‐label , comparative clinical study . Setting . Gynecology center in Norway . Population . One hundred and ten women ( 20–35 years old ) actively seeking contraception . Methods . For 26 consecutive 28‐day cycles , women received one of the following two treatments : NOMAC/E2 ( 2.5 mg/1.5 mg ) in a 24/4‐day regimen ( n= 56 ) ; or LNG/EE ( 150 μg/30 μg ) in a 21/7‐day regimen ( n= 54 ) . Main outcome measures . Bone mineral density of the lumbar spine , femoral neck , hip and trochanter ( measured by dual energy X‐ray absorptiometry ) ; associated z‐scores of the lumbar spine and femoral neck . Results . In NOMAC/E2 users , mean ( ±SD ) z‐score change from baseline for lumbar spine and femoral neck were 0.019 ± 0.242 and −0.007 ± 0.228 , respectively , vs. 0.121 ± 0.269 and 0.044 ± 0.253 in LNG/EE users , respectively . Differences between treatment groups were not significant ( p= 0.19 and p= 0.57 , respectively ) . There were no significant differences between changes in hip and trochanter z‐scores between NOMAC/E2 and LNG/EE treatments . Conclusions . After two years , NOMAC/E2 had no clinical ly relevant effect on bone mineral density . No significant difference in the effect on bone mineral density between NOMAC/E2 and LNG/EE was observed CONTEXT It is estimated that 80 % of all women have used oral contraceptives ( OCP ) , but OCP use may prevent attainment of maximal peak bone mass in young women and thus increase the risk of osteoporosis later in life . OBJECTIVE This study examined whether increased calcium intake could reduce the detrimental effects of OCP use on bone mass in young women . DESIGN The study design was a 1-yr intervention . SETTING The study was performed in a general community setting . SUBJECTS One hundred fifty-four young ( 18 - 30 yr old ) healthy women with a dietary calcium intake of less than 800 mg/d began the study , and 135 completed the trial . INTERVENTION Subjects were r and omly assigned to one of three diet intervention groups : 1 ) control , continuous established ( < 800 mg/d ) dietary calcium intake ; 2 ) medium dairy , increase calcium intake to approximately 1000 - 1100 mg/d ; and 3 ) high dairy , increase calcium intake to approximately 1200 - 1300 mg/d . R and omization was stratified by OCP use . MAIN OUTCOME MEASURES The main outcome measures were total body bone mineral density ( BMD ) and content ( BMC ) ; total hip BMD , BMC , and bone area ; and spine BMD , BMC , and bone area . RESULTS Dairy product intervention positively impacted the percentage change in total hip BMD and BMC . In addition , dairy product intake prevented a negative percentage change in total hip and spine BMD in OCP users . CONCLUSION Dairy product intake , at levels necessary to achieve the recommended intakes of calcium , protected the total hip BMD and spine BMD from loss observed in young healthy women with low calcium intakes who were using OCP OBJECTIVE : To compare the effects of a new 21-day combined oral contraceptive containing 30 μg ethinyl/estradiol plus 3 mg drospirenone with a 21-day preparation containing 30 μg ethinyl/estradiol plus 75 μg gestodene on bone turnover and bone mineral density in young fertile women . METHODS : A r and omized , controlled trial was conducted with healthy fertile women treated with 30 μg ethinyl/estradiol plus 3 mg drospirenone ( group A ; n = 24 ) , 30 μg ethinyl/estradiol plus 75 μg gestodene ( group B ; n = 24 ) and healthy controls ( group C , n = 23 ) . At 3 , 6 , 9 , and 12 months of the study , serum and urinary calcium , osteocalcin , urinary pyridinoline , and deoxypyridinoline were measured . At baseline and after 12 months , lumbar bone mineral density was determined by dual-energy X-ray absorptiometry . RESULTS : In groups A and B , urinary pyridinoline and deoxypyridinoline at 6 , 9 , and 12 months were significantly reduced in comparison with basal values and group C ( P < .05 ) . Pyridinoline and deoxypyridinoline levels were lower in group A than in group B throughout the study , but not significantly . In group A serum calcium levels were significantly increased after 6 months . At 12 months , no significant difference was detected in lumbar bone mineral density values among the 3 groups and in comparison with basal values . CONCLUSION : Both combined oral contraceptives exert a similar positive influence on bone turnover and bone-sparing effect in young postadolescent women . LEVEL OF EVIDENCE : OBJECTIVE To test for the possible association of past oral contraceptive ( OC ) use and incident fracture after menopause . DESIGN A prospect i ve cohort of 93,725 postmenopausal women . SETTING Forty Women 's Health Initiative ( WHI ) clinical centers across the United States . PATIENT(S ) Ethnically diverse 93,725 volunteer postmenopausal women , 50 to 79 years old . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) The main outcome was self-reported incident first fracture assessed prospect ively by annual question naire . RESULT ( S ) The adjusted relative hazard ( HR ) for fracture among past OC users was 1.07 ( 95 % CI , 1.01 - 1.15 ) . Among women without any postmenopausal hormone treatment , past OC use for < or = 5 years led to an HR of 1.15 ( 95 % CI , 1.04 - 1.27 ) and for past OC use > 5 years led to an HR of 1.09 ( 95 % CI , 0.97 - 1.23 ) compared with never users . CONCLUSION ( S ) This study does not support the idea that past OC use protects against later fracture This 2-year study compared Mesigyna(R ) administered to 49 pre-menopausal women between 38 and 50 years , to 99 women fitted with an IUD ( Nova-T ) . A complete lipoprotein assessment was carried out before treatment and at 6 , 12 , and 24 months of treatment . A bone densitometry was performed on half of the women , and an endometrial biopsy was taken from half of the Meisgyna group before and at the end of the first and second year . No pregnancy occurred with Mesigyna use while three pregnancies were observed with the IUD . The incidence of bleeding anomalies was higher in the Mesigyna group , with a discontinuation rate for these reasons of 20 % versus 4 % for IUD ( p < 0.05 ) . The duration of bleeding days as well as dysmenorrhea were less with Mesigyna . No differences were seen in the pattern of intermenstrual bleeding and spinal bone density between both groups . No patient developed endometrial hyperplasia after treatment , thus endometrial risk seemed not to be increased . Total and LDL cholesterol , and apolipoproteins did not show modifications . A slight decrease in total triglycerides , HDL and HDL(2 ) cholesterol , and IDL lipoproteins was observed with Mesigyna . The present study appears to be the first using a monthly injectable hormonal contraceptive and monitoring its influence on lipid patterns in premenopausal women . Mesigyna proved to be a highly effective and low risk agent for premenopausal users OBJECTIVE To compare the effect of depot medroxypro‐gesterone acetate ( DMPA ) and two types of oral contraceptives ( OC ) on bone mineral density ( BMD ) among women 18–33 years of age with those not using hormonal contraception . METHODS Data from 155 women were analyzed . Depot medroxyprogesterone acetate was administered to 33 women ; 63 women who chose oral contraception were r and omly assigned to receive either a norethindrone‐containing pill ( n = 28 ) or a desogestrel‐containing pill ( n = 35 ) . Fifty‐nine women who did not use hormonal contraception served as controls . Lumbar spine BMD was determined using dual‐energy x‐ray absorptiometry at baseline and after 12 months of contraceptive use . We analyzed method ‐related percent change in BMD while controlling for body mass index , calcium intake , exercise , and smoking . We had approximately 90 % power to detect a 2.5 % difference between any two groups . RESULTS Users of DMPA experienced a mean BMD loss of 2.74 % over 12 months compared with controls who sustained a 0.37 % loss ( P = .01 ) . Users of OCs generally demonstrated a gain ( 2.33 % for norethindrone‐containing pills , 0.33 % for desogestrel‐containing pills ) , which was different from controls among users of norethindrone‐containing pills ( P = .01 ) , but not among users of desogestrel‐containing pills ( P = .99 ) . Observed changes in BMD among DMPA users differed from women who used either type of pill ( P < .002 ) . CONCLUSION Depot medroxyprogesterone acetate has an adverse effect on BMD , in comparison with OCs or non‐hormonal methods , when used for 12 months . Results must be interpreted cautiously until it is determined whether these effects endure or are reversible OBJECTIVE : To measure the effect of 24 months of depot medroxyprogesterone acetate use on bone mineral density compared with oral contraception ( pills ) and nonhormonal contraception . METHODS : Women aged 18–33 years self-selected oral contraception , depot medroxyprogesterone acetate , or nonhormonal contraception ( controls ) . Those selecting pills were r and omized to formulations containing either 35 & mgr;g ethinyl estradiol and norethindrone or 30 & mgr;g ethinyl estradiol and desogestrel . Controls were frequency matched on age and race/ethnicity to hormonal contraception users . Dual-energy X-ray absorptiometry of the lumbar spine ( L1–L4 ) was performed at baseline , 12 months , and 24 months . Percent change in bone mineral density was analyzed by using analysis of covariance , adjusting for age , race/ethnicity , weight-bearing exercise , calcium intake , smoking status , and body mass index . RESULTS : Of the 191 women making up the final sample , 86 used pills , 47 used depot medroxyprogesterone acetate , and 58 used nonhormonal contraception . Women using depot medroxyprogesterone acetate for 24 months experienced , on average , a 5.7 % loss in bone mineral density , with a 3.2 % loss occurring between months 12 and 24 . On average , users of desogestrel pills experienced a 2.6 % loss in bone mineral density after 24 months . Bonferroni-adjusted pairwise comparisons demonstrated that bone mineral density changes from baseline to 24 months among depot medroxyprogesterone acetate users differed significantly from changes experienced by either of the pill groups or the control group . Changes in bone mineral density among users of either pill did not significantly differ from each other or from controls . CONCLUSION : Loss of bone mineral density associated with depot medroxyprogesterone acetate use appears to be linear during the first 2 years of use . Shifts in bone mineral density among pill users were not significant when compared with controls . LEVEL OF EVIDENCE : OBJECTIVES To evaluate the pattern of mineral density in eumenorrhoic and oligomenorrhoic perimenopausal women , and assess the effects of different low dose oral contraceptives ( OC ) on bone metabolism and spine bone density . METHODS Spine bone density was evaluated in a longitudinal 2-year follow-up , r and omized , unblinded , uncontrolled clinical trial conducted in healthy , normally menstruating perimenopausal women , perimenopausal oligomenorrhoic women and in perimenopausal oligomenorrhoic women treated with an oral contraceptive containing 20 microg ethinyl estradiol plus 0.15 mg desogestrel , 0.100 mg levonorgestrel , 0.75 mg of gestodene ( n=15 in each group ) . The results were analyzed by factorial or repeated measures analysis of variance , as appropriate . RESULTS During the observation period , in normal menstruating women there were no changes in menstrual cycle , plasma FSH and estradiol levels , and spine bone density . In oligomenorrhoic untreated women an increase in cycle length , with a concomitant decrease in plasma estradiol and an increase in plasma FSH levels were evidence d ( p<0.05 ) . In this group a significant decrease in bone density ( p<0.05 ) occurred . In OC-treated women , a significant ( p<0.05 ) increase in bone density was observed , with no differences among different groups . CONCLUSION Different progestins used in OC preparations do not modify the bone sparing effect of perimenopausal OC administration avoiding the decrease in bone density BACKGROUND The aim was to evaluate changes of bone mineral density ( BMD ) and markers of bone turnover in healthy adolescents , and in adolescent users of combined oral contraceptives ( COCs ) with different ethinylestradiol ( EE ) contents . METHODS In this prospect i ve crossover study , 56 healthy females ( 15 - 19.5 years ) with desire to use hormonal contraception were r and omized to COC with either 30 or 15 μg of EE in crossover design of 9-month intervention each in reverse order . Nonusers of the same age ( n=28 ) served as controls . BMD at lumbar spine ( LS ) , total femur , femoral neck , distal radius , and total body , and serum markers ( N-propeptide of type I procollagen , and type I collagen C-telopeptide ) were measured at baseline and after 9 and 18 months . RESULTS In COC nonusers , BMD significantly increased at LS and radius , while markers decreased . In COC users , BMD did not increase , with the exception of LS BMD in the 30 μg COC group ( P<0.05 ) . In the crossover design , a difference between the low- and very low-dose COC users was found in LS BMD changes ( P<0.05 ) , where increase in BMD was more impaired in the 15 μg COC users . The skeletal effects of COC remained significant after adjustments for age and smoking status . Markers declined faster in COC users during the first period , while they remained stable or even increased during the second 9 months . CONCLUSION Physiological acquisition of LS BMD during adolescent age may be prevented by use of COC , especially those containing very low dose of EE BACKGROUND The effects of a 21-day combined oral contraceptive containing 30 mcg ethinyl estradiol plus 3 mg drospirenone with a 21-day preparation containing 20 mcg ethinyl estradiol plus 3 mg drospirenone on bone turnover and bone mineral density ( BMD ) in young fertile women were compared . METHODS A r and omized , controlled trial was conducted on healthy fertile women treated with 30 mcg ethinyl estradiol plus 3 mg drospirenone ( Group A ; n=21 ) , 20 mcg ethinyl estradiol plus 3 mg drospirenone ( Group B ; n=23 ) and healthy controls ( Group C ; n=21 ) . At 3 , 6 , 9 and 12 months , serum and urinary calcium , osteocalcin ( BGP ) , urinary pyridinoline and deoxypyridinoline were measured . At baseline and after 12 months , lumbar bone mineral density was determined by dual-energy X-ray absorptiometry . RESULTS In Groups A and B , urinary pyridinoline and deoxypyridinoline at 6 , 9 and 12 months were significantly reduced in comparison with basal values and Group C ( p<.05 ) . In Groups A and B , serum calcium levels were significantly increased after 6 months . No significant difference was detected between Groups A and B in urinary levels of pyridinoline and deoxypyridinoline , in calcium levels and in BGP levels . At 12 months , no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values . CONCLUSION Both combined oral contraceptives exert a similar positive influence on bone turnover in young postadolescent women |
10,391 | 30,037,340 | However , positive MRD prior to transplantation was not associated with a higher rate of nonrelapse mortality . | Background This meta- analysis was performed to explore the impact of minimal residual disease ( MRD ) prior to transplantation on the prognosis for patients with acute lymphoblastic leukemia ( ALL ) . | BACKGROUND The level of minimal residual disease during remission induction is the most important prognostic indicator in patients with acute lymphoblastic leukaemia ( ALL ) . We aim ed to establish the clinical significance of minimal residual disease in a prospect i ve trial that used sequential minimal residual disease measurements to guide treatment decisions . METHODS Between June 7 , 2000 , and Oct 24 , 2007 , 498 assessable patients with newly diagnosed ALL were enrolled in a clinical trial at St Jude Children 's Research Hospital . We provisionally classified the risk of relapse as low , st and ard , or high according to patients ' baseline clinical and laboratory features . Final risk assignment to establish treatment intensity was based mainly on minimal residual disease levels measured on days 19 and 46 of remission induction , and on week 7 of maintenance treatment . Additional measurements of minimal residual disease were made on weeks 17 , 48 , and 120 ( end of treatment ) . The primary aim was to establish the association between event-free survival and patients ' minimal residual disease levels during remission induction and sequentially post-remission . This trial was registered at Clinical Trials.gov , number NCT00137111 . FINDINGS Irrespective of the provisional risk classification , 10-year event-free survival was significantly worse for patients with 1 % or greater minimal residual disease levels on day 19 compared with patients with lower minimal residual disease levels ( 69·2 % , 95 % CI 49·6 - 82·4 , n=36 vs 95·5 % , 91·7 - 97·5 , n=244 ; p<0·001 for the provisional low-risk group and 65·1 % , 50·7 - 76·2 , n=56 vs 82·9 % , 75·6 - 88·2 , n=142 ; p=0·01 for the provisional st and ard-risk group ) . 12 patients with provisional low-risk ALL and 1 % or higher minimal residual disease levels on day 19 but negative minimal residual disease ( < 0·01 % ) on day 46 were treated for st and ard-risk ALL and had a 10-year event-free survival of 88·9 % ( 43·3 - 98·4 ) . For the 280 provisional low-risk patients , a minimal residual disease level of less than 1 % on day 19 predicted a better outcome , irrespective of the minimal residual disease level on day 46 . Of provisional st and ard-risk patients with minimal residual disease of less than 1 % on day 19 , the 15 with persistent minimal residual disease on day 46 seemed to have an inferior 10-year event-free survival compared with the 126 with negative minimal residual disease ( 72·7 % , 42·5 - 88·8 vs 84·0 % , 76·3 - 89·4 ; p=0·06 ) after receiving the same post-remission treatment for st and ard-risk ALL . Of patients attaining negative minimal residual disease status after remission induction , minimal residual disease re-emerged in four of 382 studied on week 7 , one of 448 at week 17 , and one of 437 at week 48 ; all but one of these six patients died despite additional treatment . By contrast , relapse occurred in only two of the 11 patients who had decreasing minimal residual disease levels between the end of induction and week 7 of maintenance therapy and were treated with chemotherapy alone . INTERPRETATION Minimal residual disease levels during remission induction treatment have important prognostic and therapeutic implication s even in the context of minimal residual disease-guided treatment . Sequential minimal residual disease monitoring after remission induction is warranted for patients with detectable minimal residual disease . FUNDING National Institutes of Health and American Lebanese Syrian Associated Charities The efficacy of allografting in acute lymphoblastic leukemia ( ALL ) is heavily influenced by remission status at the time of transplant . Using polymerase chain reaction (PCR)-based minimal residual disease ( MRD ) analysis , we have investigated retrospectively the impact of su bmi croscopic leukemia on outcome in 64 patients receiving allogeneic bone marrow transplantation ( BMT ) for childhood ALL . Remission BM specimens were taken 6 to 81 days ( median , 23 ) before transplant . All patients received similar conditioning therapy ; 50 received grafts from unrelated donors and 14 from related donors . Nineteen patients were transplanted in first complete remission ( CR1 ) and 45 in second or subsequent CR . MRD was analyzed by PCR of Ig or T-cell receptor delta or gamma rearrangements , electrophoresis , and allele-specific oligoprobing . Sample s were rated high-level positive ( clonal b and evident after electrophoresis ; sensitivity 10(-2 ) to 10(-3 ) ) , low-level positive ( MRD detected only after oligoprobing ; sensitivity 10(-3 ) to 10(-5 ) ) , or negative . Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse ( all MRD- ) , MRD was detected at high level in 12 patients , low level in 11 , and was undetectable in 33 . Two-year event-free survival for these groups was 0 % , 36 % , and 73 % , respectively ( P < .001 ) . Follow-up in patients remaining in continuing remission is 20 to 96 months ( median , 35 ) . These results suggest that MRD analysis could be used routinely in this setting . This would allow identification of patients with resistant leukemia ( who may benefit from innovative BMT protocol s ) and of those with more responsive disease ( who may be c and i date s for r and omized trials of BMT versus modern intensive relapse chemotherapy ) Minimal residual disease ( MRD ) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia ( ALL ) . Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse . Between 2005 and 2008 , we conducted a prospect i ve study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non‐ex vivo T depleted myeloablative transplantation . Immunoglobulin (Ig)H/T‐cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high‐risk paediatric ALL enrolled . There were no significant demographic differences except remission status ( first or second complete remission ) between the 95 children with MRD < 10−3 and the 27 with MRD ≥10−3 . Multivariate analysis identified sex match and MRD as being significantly associated with 5‐year survival . MRD ≥10−3 compromised the 5‐year cumulative incidence of relapse ( 43·6 vs. 16·7 % ) . Complete remission status and stem cell source did not modify the relationship between MRD and prognosis . Thus , pre‐transplant MRD is still a major predictor of outcome for ALL . The MRD‐guided strategy result ed in survival for 72·3 % of patients with MRD<10−3 and 40·4 % of those with MRD ≥10−3 Relapse of pediatric acute lymphoblastic leukemia ( ALL ) remains the main cause of treatment failure after allogeneic stem cell transplantation ( alloSCT ) . A high level of minimal residual disease ( MRD ) before alloSCT has been shown to predict these relapses . Patients at risk might benefit from a preemptive alloimmune intervention . In this first prospect i ve , MRD-guided intervention study , 48 patients were stratified according to pre-SCT MRD level . Eighteen children with MRD level ⩾1 × 10−4 were eligible for intervention , consisting of early cyclosporine A tapering followed by consecutive , incremental donor lymphocyte infusions ( n=1–4 ) . The intervention was associated with graft versus host disease ⩾ grade II in only 23 % of patients . Event-free survival in the intervention group was 19 % . However , in contrast with the usual early recurrence of leukemia , relapses were delayed up to 3 years after SCT . In addition , several relapses presented at unusual extramedullary sites suggesting that the immune intervention may have altered the pattern of leukemia recurrence . In 8 out of 11 evaluable patients , relapse was preceded by MRD recurrence ( median 9 weeks , range 0–30 ) . We conclude that in children with high-risk ALL , immunotherapy-based regimens after SCT are feasible and may need to be further intensified to achieve total eradication of residual leukemic cells PURPOSE Minimal residual disease ( MRD ) before allogeneic stem-cell transplantation was shown to predict outcome in children with relapsed acute lymphoblastic leukemia ( ALL ) in retrospective analysis . To verify this , the Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster ( ALL-REZ BFM ) Study Group conducted a prospect i ve trial . PATIENTS AND METHODS Between March 1999 and July 2005 , 91 children with relapsed ALL treated according to the ALL-REZ BFM 96 or 2002 protocol s and receiving stem-cell transplantation in > or= second remission were enrolled . MRD quantification was performed by real-time polymerase chain reaction using T-cell receptor and immunoglobulin gene rearrangements . RESULTS Probability of event-free survival ( pEFS ) and cumulative incidence of relapse ( CIR ) in 45 patients with MRD > or= 10(-4 ) leukemic cells was 0.27 and 0.57 compared with 0.60 and 0.13 in 46 patients with MRD less than 10(-4 ) leukemic cells ( EFS , P = .004 ; CIR , P < .001 ) . Intermediate-risk patients ( strategic group S1 ) with MRD > or= 10(-4 ) leukemic cells ( n = 14 ) had a pEFS of 0.20 and CIR of 0.73 , whereas patients with MRD less than 10(-4 ) leukemic cells ( n = 21 ) had a pEFS of 0.68 and CIR of 0.09 ( EFS , P = .020 ; CIR , P < .001 ) . High-risk patients ( S3/4 , third complete remission ) who received transplantation with an MRD load of less than 10(-4 ) leukemic cells ( n = 25 ) showed a pEFS and CRI of 0.53 and 0.18 , respectively . In contrast , pEFS and CRI were 0.30 and 0.50 in patients who received transplantation with an MRD load of > or= 10(-4 ) leukemic cells . Multivariate Cox regression analysis revealed MRD as the only independent parameter predictive for EFS ( P = .006 ) . CONCLUSION MRD is an important predictor for post-transplantation outcome . As a result , new strategies with modified stem-cell transplantation procedures will be evaluated in ALL-BFM trials Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia . Despite improvements in the up-front therapy , survival after relapse is still relatively poor , especially for high-risk relapses . The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment ; to vali date currently used risk stratifications , and identify additional prognostic factors for overall survival . Altogether , 516 of 2735 patients ( 18.9 % ) relapsed between 1992 and 2011 and were included in the study . There were no statistically significant differences in outcome between the up-front protocol s or between the relapse protocol s used , but an improvement over time was observed . The 5-year overall survival for patients relapsing in the period 2002–2011 was 57.5±3.4 % , but 44.7±3.2 % ( P<0.001 ) if relapse occurred in the period 1992–2001 . Factors independently predicting mortality after relapse included short duration of first remission , bone marrow involvement , age ten years or over , unfavorable cytogenetics , and Down syndrome . T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis . The outcome for early combined pre-B relapses was unexpectedly poor ( 5-year overall survival 38.0±10.6 % ) , which supports the notion that these patients need further risk adjustment . Although survival outcomes have improved over time , the development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia BACKGROUND We sought to improve outcome in patients with childhood acute myeloid leukaemia ( AML ) by applying risk-directed therapy that was based on genetic abnormalities of the leukaemic cells and measurements of minimal residual disease ( MRD ) done by flow cytometry during treatment . METHODS From Oct 13 , 2002 , to June 19 , 2008 , 232 patients with de-novo AML ( n=206 ) , therapy-related or myelodysplasia-related AML ( n=12 ) , or mixed-lineage leukaemia ( n=14 ) were enrolled at eight centres . 230 patients were assigned by block , non-blinded r and omisation , stratified by cytogenetic or morphological subtype , to high-dose ( 18 g/m(2 ) , n=113 ) or low-dose ( 2 g/m(2 ) , n=117 ) cytarabine given with daunorubicin and etoposide ( ADE ; induction 1 ) . The primary aim of the study was to compare the incidence of MRD positivity of the high-dose group and the low-dose group at day 22 of induction 1 . Induction 2 consisted of ADE with or without gemtuzumab ozogamicin ( GO anti-CD33 monoclonal antibody ) ; consolidation therapy included three additional courses of chemotherapy or haematopoietic stem-cell transplantation ( HSCT ) . Levels of MRD were used to allocate GO and to determine the timing of induction 2 . Both MRD and genetic abnormalities at diagnosis were used to determine the final risk classification . Low-risk patients ( n=68 ) received five courses of chemotherapy , whereas high-risk patients ( n=79 ) , and st and ard-risk patients ( n=69 ) with matched sibling donors , were eligible for HSCT ( done for 48 high-risk and eight st and ard-risk patients ) . All 230 r and omised patients were analysed for the primary endpoint . Other analyses were limited to the 216 patients with AML , excluding those with mixed-lineage leukaemia . This trial is closed to accrual and is registered with Clinical Trials.gov , number NCT00136084 . FINDINGS Complete remission was achieved in 80 % ( 173 of 216 patients ) after induction 1 and 94 % ( 203 of 216 ) after induction 2 . Induction failures included two deaths from toxic effects and ten cases of resistant leukaemia . The introduction of high-dose versus low-dose cytarabine did not significantly lower the rate of MRD-positivity after induction 1 ( 34%vs 42 % , p=0.17 ) . The 6-month cumulative incidence of grade 3 or higher infection was 79.3 % ( SE 4.0 ) for patients in the high-dose group and 75.5 % ( 4.2 ) for the low-dose group . 3-year event-free survival and overall survival were 63.0 % ( SE 4.1 ) and 71.1 % ( 3.8 ) , respectively . 80 % ( 155 of 193 ) of patients achieved MRD of less than 0.1 % after induction 2 , and the cumulative incidence of relapse for this group was 17 % ( SE 3 ) . MRD of 1 % or higher after induction 1 was the only significant independent adverse prognostic factor for both event-free ( hazard ratio 2.41 , 95 % CI 1.36 - 4.26 ; p=0.003 ) and overall survival ( 2.11 , 1.09 - 4.11 ; p=0.028 ) . INTERPRETATION Our findings suggest that the use of targeted chemotherapy and HSCT , in the context of a comprehensive risk-stratification strategy based on genetic features and MRD findings , can improve outcome in patients with childhood AML . FUNDING National Institutes of Health and American Lebanese Syrian Associated Charities ( ALSAC ) Data on pretransplantation minimal residual disease ( MRD ) and outcomes of umbilical cord blood transplantation ( UCBT ) are limited . Out of the 143 patients with acute lymphoblastic leukemia ( ALL ) who underwent UCBT at the University of Minnesota between 2004 and 2010 , we evaluated 86 patients with available MRD assessment data by 4- and 8-color flow cytometry analysis immediately before transplantation . Ten patients ( 11.6 % ) were MRD-positive , and 76 were MRD-negative ( 88.4 % ) . Most of the patients ( 82 % ) received myeloablative conditioning . GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil . In multivariate analysis , age , disease status ( complete remission [ CR ] 1 versus CR2/CR3 ) , disease group ( precursor B cell ALL versus Philadelphia chromosome-positive ALL versus T cell ALL ) , and time to transplantation had no impact on relapse . Patients with MRD before UCBT had a greater incidence of relapse at 2 years ( relapse rate , 30 % ; 95 % confidence interval [ CI ] , 4%-56 % ) and lower 3-year disease-free survival ( 30 % ; 95 % CI , 7%-58 % ) compared with those without MRD ( relapse rate , 16 % ; 95 % CI , 8%-25 % ; P = .05 ; disease-free survival , 55 % ; 95 % CI , 43%-66 % ; P = .02 ) . Our data suggest that in patients with ALL , achieving an MRD-negative state before UCBT improves outcomes BACKGROUND Minimal residual disease ( MRD ) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia ( ALL ) during remission . We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification . METHODS Between Oct 1 , 2003 and June 30 , 2011 , consecutive children and young adults ( aged 1 - 25 years ) with ALL from the UK and Irel and were recruited . Eligible patients were categorised into clinical st and ard , intermediate , and high risk groups on the basis of a combination of National Cancer Institute ( NCI ) criteria , cytogenetics , and early response to induction therapy , which was assessed by bone marrow blast counts taken at days 8 ( NCI high-risk patients ) and 15 ( NCI st and ard-risk patients ) after induction began . Clinical st and ard-risk and intermediate-risk patients were assessed for MRD . Those classified as MRD low risk ( undetectable MRD at the end of induction [ day 29 ] or detectable MRD at day 29 that became undetectable by week 11 ) were r and omly assigned to receive one or two delayed intensification courses . Patients had received induction , consolidation , and interim maintenance therapy before they began delayed intensification . Delayed intensification consisted of pegylated asparaginase on day 4 ; vincristine , dexamethasone ( alternate weeks ) , and doxorubicin for 3 weeks ; and 4 weeks of cyclophosphamide and cytarabine . Computer r and omisation was done with stratification by MRD result and balancing for sex , age , and white blood cell count at diagnosis by method of minimisation . Patients , clinicians , and data analysts were not masked to treatment allocation . The primary outcome was event-free survival ( EFS ) , which was defined as time to relapse , secondary tumour , or death . Our aim was to rule out a 7 % reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses . Analyses were by intention to treat . This trial is registered , number IS RCT N07355119 . FINDINGS Of 3207 patients registered in the trial overall , 521 MRD low-risk patients were r and omly assigned to receive one ( n=260 ) or two ( n=261 ) delayed intensification courses . Median follow-up of these patients was 57 months ( IQR 42 - 72 ) . We recorded no significant difference in EFS between the group given one delayed intensification ( 94·4 % at 5 years , 95 % CI 91·1 - 97·7 ) and that given two delayed intensifications ( 95·5 % , 92·8 - 98·2 ; unadjusted odds ratio 1·00 , 95 % CI 0·43 - 2·31 ; two-sided p=0·99 ) . The difference in 5-year EFS between the two groups was 1·1 % ( 95 % CI -5·6 to 2·5 ) . 11 patients ( actuarial relapse at 5 years 5·6 % , 95 % CI 2·3 - 8·9 ) given one delayed intensification and six ( 2·4 % , 0·2 - 4·6 ) given two delayed intensifications relapsed ( p=0·23 ) . Three patients ( 1·2 % , 0 - 2·6 ) given two delayed intensifications died of treatment-related causes compared with none in the group given one delayed intensification ( p=0·08 ) . We recorded no significant difference between groups for serious adverse events and grade 3 or 4 toxic effects ; however , the second delayed intensification course was associated with one ( < 1 % ) treatment-related death , and 74 episodes of grade 3 or 4 toxic effects in 45 patients ( 17 % ) . INTERPRETATION Treatment reduction is feasible for children and young adults with ALL who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD by the end of induction therapy . FUNDING Medical Research Council and Leukaemia and Lymphoma Research An international collaboration was set up to prospect ively evaluate the role of allogeneic transplantation for adults with acute lymphoblastic leukemia ( ALL ) and compare autologous transplantation with st and ard chemotherapy . Patients received 2 phases of induction and , if in remission , were assigned to allogeneic transplantation if they had a compatible sibling donor . Other patients were r and omized to chemotherapy for 2.5 years versus an autologous transplantation . A donor versus no-donor analysis showed that Philadelphia chromosome-negative patients with a donor had a 5-year improved overall survival ( OS ) , 53 % versus 45 % ( P = .01 ) , and the relapse rate was significantly lower ( P < or = .001 ) . The survival difference was significant in st and ard-risk patients , but not in high-risk patients with a high nonrelapse mortality rate in the high-risk donor group . Patients r and omized to chemotherapy had a higher 5-year OS ( 46 % ) than those r and omized to autologous transplantation ( 37 % ; P = .03 ) . Matched related allogeneic transplantations for ALL in first complete remission provide the most potent antileukemic therapy and considerable survival benefit for st and ard-risk patients . However , the transplantation-related mortality for high-risk older patients was unacceptably high and abrogated the reduction in relapse risk . There is no evidence that a single autologous transplantation can replace consolidation/maintenance in any risk group . This study is registered at http:// clinical trials.gov as NCT00002514 Summary Background Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades , the outcome of those who relapse has remained static . We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens . Methods This open-label r and omised trial was undertaken in 22 centres in the UK and Irel and and nine in Australia and New Zeal and . Patients aged 1–18 years with first relapse of acute lymphoblastic leukaemia were stratified into high-risk , intermediate-risk , and st and ard-risk groups on the basis of duration of first complete remission , site of relapse , and immunophenotype . All patients were allocated to receive either idarubicin or mitoxantrone in induction by stratified concealed r and omisation . Neither patients nor those giving interventions were masked . After three blocks of therapy , all high-risk group patients and those from the intermediate group with postinduction high minimal residual disease ( ≥10−4 cells ) received an allogenic stem-cell transplant . St and ard-risk and intermediate-risk patients with postinduction low minimal residual disease ( < 10−4 cells ) continued chemotherapy . The primary outcome was progression-free survival and the method of analysis was intention-to-treat . R and omisation was stopped in December , 2007 because of differences in progression-free and overall survival between the two groups . This trial is registered , reference number ISCRTN45724312 . Findings Of 239 registered patients , 216 were r and omly assigned to either idarubicin ( 109 analysed ) or mitoxantrone ( 103 analysed ) . Estimated 3-year progression-free survival was 35·9 % ( 95 % CI 25·9–45·9 ) in the idarubicin group versus 64·6 % ( 54·2–73·2 ) in the mitoxantrone group ( p=0·0004 ) , and 3-year overall survival was 45·2 % ( 34·5–55·3 ) versus 69·0 % ( 58·5–77·3 ; p=0·004 ) . Differences in progression-free survival between groups were mainly related to a decrease in disease events ( progression , second relapse , disease-related deaths ; HR 0·56 , 0·34–0·92 , p=0·007 ) rather than an increase in adverse treatment effects ( treatment death , second malignancy ; HR 0·52 , 0·24–1·11 , p=0·11 ) . Interpretation As compared with idarubicin , mitoxantrone conferred a significant benefit in progression-free and overall survival in children with relapsed acute lymphobastic leukaemia , a potentially useful clinical finding that warrants further investigation . Funding Cancer Research UK , Leukaemia and Lymphoma Research , Cancer Council NSW , and Sporting Chance Cancer Foundation We investigated prognostic factors for the clinical outcome of allogeneic hematopoietic stem cell transplantation ( allo-HSCT ) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia ( Ph+ALL ) following imatinib-based therapy . Among 100 adult patients who were prospect ively enrolled in the JALSG Ph+ALL202 study , 97 patients obtained complete remission ( CR ) by imatinib-combined chemotherapy , among whom 60 underwent allo-HSCT in their first CR . The probabilities of overall survival ( OS ) and disease-free survival ( DFS ) at 3 years after HSCT were 64 % ( 95 % CI , 49–76 ) and 58 % ( 95 % CI , 43–70 ) , respectively . Prognostic factor analysis revealed that the major BCR – ABL transcript was the only unfavorable predictor for OS and DFS after HSCT by both univariate ( HR , 3.67 ( 95 % CI 1.49–9.08 ) ; P=0.005 and HR , 6.25 ( 95 % CI , 1.88–20.8 ) ; P=0.003 , respectively ) and multivariate analyses ( HR , 3.20 ( 95 % CI , 1.21–8.50 ) ; P=0.019 and HR , 6.92 ( 95 % CI , 2.09–22.9 ) ; P=0.002 , respectively ) . Minimal residual disease status at the time of HSCT had a significant influence on relapse rate ( P=0.015 ) . Further study of the BCR – ABL subtype for the clinical impact on outcome of allo-HSCT in Ph+ALL is warranted BACKGROUND The level of minimal residual disease ( MRD ) prior to allogeneic hematopoietic stem cell transplantation ( HSCT ) has been shown to be an independent prognostic factor for outcome of pediatric patients with high-risk acute lymphoblastic leukemia ( ALL ) . Retrospective studies which used ( semi- ) quantitation of clone-specific immunoglobulin/T-cell receptor ( Ig/TCR ) rearrangements have documented the feasibility and practicality of this technique . This approach has also been disputed due to the occurrence of clonal evolution and generally high MRD levels prior to HSCT . PROCEDURE In our prospect i ve study , MRD before and after HSCT was monitored using quantitative real-time PCR in a cohort of 36 children with ALL consecutively transplanted in our center between VIII/2000 and VII/2004 . RESULTS In 25 of 36 patients , MRD level prior HSCT was assessed . Seventeen patients were classified as MRD-negative and eight were MRD-positive up to 9 x 10(-2 ) . In MRD-positive subgroup , seven events ( six relapses ) occurred post-transplant in striking contrast to only one relapse in MRD-negative subgroup ( event-free survival ( EFS ) log-rank P < 0.0001 ) . MRD proved to be the only significant prognostic factor in a multivariate analysis ( P < 0.0001 ) . Adoptive immunotherapy including donor lymphocyte infusions in patients with adverse dynamics of MRD after HSCT had only limited and /or temporary effect . Clonal evolution did not present a problem precluding MRD monitoring in any of patients suffering a post-transplant relapse . CONCLUSIONS We show that MRD quantitation using clonal Ig/TCR rearrangements successfully assesses the risk in pediatric ALL patients undergoing allogeneic HSCT . As our ability to treat detectable MRD levels after HSCT is very limited , alternative strategies for MRD-positive patients prior HSCT are necessary Minimal residual disease ( MRD ) during early chemotherapy is a powerful predictor of relapse in acute lymphoblastic leukaemia ( ALL ) and is used in children to determine eligibility for allogeneic haematopoietic stem cell transplantation ( HSCT ) in first ( CR1 ) or later complete remission ( CR2/CR3 ) . Variables affecting HSCT outcome were analysed in 81 children from the ANZCHOG ALL8 trial . The major cause of treatment failure was relapse , with a cumulative incidence of relapse at 5 years ( CIR ) of 32 % and treatment‐related mortality of 8 % . Leukaemia‐free survival ( LFS ) and overall survival ( OS ) were similar for HSCT in CR1 ( LFS 62 % , OS 83 % , n = 41 ) or CR2/CR3 ( LFS 60 % , OS 72 % , n = 40 ) . Patients achieving bone marrow MRD negativity pre‐HSCT had better outcomes ( LFS 83 % , OS 92 % ) than those with persistent MRD pre‐HSCT ( LFS 41 % , OS 64 % , P < 0·0001 ) or post‐HSCT ( LFS 35 % , OS 55 % , P < 0·0001 ) . Patients with B‐other ALL had more relapses ( CIR 50 % , LFS 41 % ) than T‐ALL and the main precursor‐B subtypes including BCR‐ABL1 , KMT2A ( MLL ) , ETV6‐RUNX1 ( TEL‐AML1 ) and hyperdiploidy > 50 . A Cox multivariate regression model for LFS retained both B‐other ALL subtype ( hazard ratio 4·1 , P = 0·0062 ) and MRD persistence post‐HSCT ( hazard ratio 3·9 , P = 0·0070 ) as independent adverse prognostic variables . Persistent MRD could be used to direct post‐HSCT therapy PURPOSE To eluci date the impact of minimal residual disease ( MRD ) after allogeneic transplantation , the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster Stem Cell Transplantation Group ( ALL-BFM-SCT ) conducted a prospect i ve clinical trial . PATIENTS AND METHODS In the ALL-BFM-SCT 2003 trial , MRD was assessed in the bone marrow at days + 30 , + 60 , + 90 , + 180 , and + 365 after transplantation in 113 patients with relapsed disease . St and ardized quantification of MRD was performed according to the guidelines of the Euro-MRD Group . RESULTS All patients showed a 3-year probability of event-free survival ( pEFS ) of 55 % . The cumulative incidence rates of relapse and treatment-related mortality were 32 % and 12 % , respectively . The pEFS was 60 % for patients who received their transplantations in second complete remission , 50 % for patients in ≥ third complete remission , and 0 % for patients not in remission ( P = .015 ) . At all time points , the level of MRD was inversely correlated with event-free survival ( EFS ; P < .004 ) and positively correlated with the cumulative incidence of relapse ( P < .01 ) . A multivariable Cox model was fitted for each time point , which showed that MRD ≥ 10(-4 ) leukemic cells was consistently correlated with inferior EFS ( P < .003 ) . The accuracy of MRD measurements in predicting relapse was investigated with time-dependent receiver operating curves at days + 30 , + 60 , + 90 , and + 180 . From day + 60 onward , the discriminatory power of MRD detection to predict the probability of relapse after 1 , 3 , 6 , and 9 months was more than 96 % , more than 87 % , more than 71 % , and more than 61 % , respectively . CONCLUSION MRD after transplantation was a reliable marker for predicting impending relapses and could thus serve as the basis for pre-emptive therapy PURPOSE We recently reported that children with acute leukemias who show increasing mixed chimerism ( MC ) after allogeneic stem-cell transplantation have a significantly enhanced risk of relapse . Here we present the results of a prospect i ve multicenter study to investigate ( 1 ) whether relapse of acute lymphoblastic leukemia ( ALL ) can be determined in advance by serial analysis of chimerism , and ( 2 ) if outcome can be influenced by withdrawal of immunosuppression and /or by low-dose donor lymphocyte infusion when increasing MC is detected . PATIENTS AND METHODS Serial and quantitative analysis of chimerism was performed using a fluorescent-based short-t and em-repeat-polymerase chain reaction in 163 children with ALL . RESULTS One hundred one patients revealed complete chimerism ( CC ) or low-level MC ( CC/low-level MC ) ; increasing MC was found in 46 patients ; and decreasing MC , in 16 patients . Relapse was significantly more frequent in patients with increasing MC ( 26 of 46 ) than in patients with CC/low-level MC ( eight of 101 ) or in patients with decreasing MC ( 0 of 16 ; P < .0001 ) . The probability of 3-year event-free survival ( EFS ) was 54 % for all patients , 66 % for patients with CC/low-level MC ( n = 101 ) , 66 % for patients with decreasing MC ( n = 16 ) , and 23 % for patients with increasing MC ( n = 46 ; P < .0001 ) . Of the 46 patients with increasing MC , 31 received immunotherapy . This group had a significantly higher 3-year EFS estimate ( 37 % ) than the 15 patients who did not receive immunotherapy ( 0 % ; P < .001 ) . CONCLUSION Serial analysis of chimerism reliably identifies patients at highest risk to relapse . The 3-year EFS of patients with increasing MC without immunotherapy was 0 % , by which overt relapse could be prevented in a considerable group of patients |
10,392 | 30,180,202 | Changes were higher after controlling for the risk of bias in upper and lower body strength and for supervised exercise in lower body strength .
Both resistance training alone and combined with aerobic exercise showed a positive change when studies with low risk of bias and professional supervision were analyzed , improving upper and , more critically , lower body muscle strength .
Also , this study found that exercise had a lowering effect on IL-6 levels in PLWH | BACKGROUND Infection with human immunodeficiency virus ( HIV ) affects muscle mass , altering independent activities of people living with HIV ( PLWH ) .
Resistance training alone ( RT ) or combined with aerobic exercise ( AE ) is linked to improved muscle mass and strength maintenance in PLWH .
These exercise benefits have been the focus of different meta-analyses , although only a limited number of studies have been identified up to the year 2013/4 .
An up-to- date systematic review and meta- analysis concerning the effect of RT alone or combined with AE on strength parameters and hormones is of high value , since more and recent studies dealing with these types of exercise in PLWH have been published . | Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials Background : Pulmonary complications , respiratory symptoms and depression are common occurrences which contribute to the morbidity and mortality seen in individuals living with HIV/AIDS . This study investigated the effect of aerobic exercise on the pulmonary functions , respiratory symptoms and psychological status of people living with HIV . Methods : This study was conducted in Lagos , Nigeria from October 2014 to May 2015 . Forty eligible individuals with HIV aged 18 yr and above participated , of which 33 cooperated to the end . They were recruited from the HIV/AIDS Prevention and Intervention Initiative ( APIN ) Clinic , Lagos University Teaching Hospital , Nigeria and were r and omly assigned to either the study or the control group . The study group received aerobic exercise training three times a week for six weeks and counselling while the control group received only counselling . Pulmonary functions , respiratory symptoms and psychological status were evaluated at baseline and at six weeks . Inferential statistics of paired and independent t-test were used to analyze the data . Results : Comparison of mean changes in the pulmonary variables of the study group with those of the control group showed significant differences in all but in the respiratory rate ( RR ) - [ Forced Expiratory Volume in one second : , P=0.001 , Forced Vital Capacity : P=0.001 , Peak Expiratory Flow : P=0.001 ] . There were also significant differences between the mean changes in respiratory symptoms ( P=0.001 ) and depressive symptoms ( P=0.001 ) of study group and those of the control group . Conclusions : Aerobic exercise training significantly improved pulmonary functions as well as significantly reduced respiratory and depressive symptoms in people living with HIV Exercise has the potential to impact disease by altering circulating anabolic and catabolic factors . It was the goal of this study to determine how different regimens of low-intensity and moderate-intensity exercise affected circulating levels of these anabolic and catabolic factors in HIV-infected men . Exercise-naive , HIV-infected men , medically cleared for study participation , were r and omized into one of the following groups : a moderate-intensity group ( MOD , who completed 30 min of moderate-intensity aerobic training followed by 30 min of moderate-intensity resistance training ; a low-intensity group ( LOW ) , who completed 60 min of treadmill walking ; or a control group ( CON ) , who attended the clinic but participated in no activity . Blood and saliva sample s were collected at selected time points before , during , and after each of the 3 required sessions . Compared with baseline , the MOD group ( n=14 ) had a 135 % increase in growth hormone ( GH ) ( p<0.05 ) and a 34 % decrease in cortisol ( CORT ) ( p<0.05 ) at the post time point , a 31 % increase in interleukin-6 ( IL-6 ) ( p<0.05 ) at 30-min post exercise , and a 23 % increase in IL-6 ( p<0.05 ) and a 13 % decrease in soluble tumor necrosis factor receptor 2 ( sTNFrII ) ( p<0.05 ) at 60-min post exercise . The LOW ( n=11 ) group had a 3.5 % decrease in sTNFrII ( < 0.05 ) at 30-min post exercise compared with baseline and a 49 % decrease ( p<0.05 ) in GH at 60-min post exercise . The CON group ( n=13 ) had a decrease in GH at 30-min ( 62 % , p<0.05 ) and 60-min ( 61 % , p<0.05 ) post exercise compared with baseline . The increase in GH from baseline to post was greater in the MOD group ( p<0.05 ) and the decrease in CORT from pre to post was greater in the MOD group ( p<0.05 ) than in the other groups . These data suggest that individual sessions of both low-intensity and moderate-intensity exercise can alter circulating anabolic and catabolic factors in HIV-infected men . The changes in the MOD group present potential mechanisms for the increases in lean tissue mass seen with resistance exercise training OBJECTIVE HIV-infected older adults ( HOA ) are at risk of functional decline . Interventions promoting physical activity that can attenuate functional decline and are easily translated into the HOA community are of high priority . We conducted a r and omized , controlled clinical trial to evaluate whether a physical activity counseling intervention based on self-determination theory ( SDT ) improves physical function , autonomous motivation , depression and the quality of life ( QOL ) in HOA . METHOD In total , 67 community-dwelling HOA with mild-to-moderate functional limitations were r and omized to 1 of 2 groups : a physical activity counseling group or the usual care control group . We used SDT to guide the development of the experimental intervention . Outcome measures that were collected at baseline and final study visits included a battery of physical function tests , levels of physical activity , autonomous motivation , depression , and QOL . RESULTS The study participants were similar in their demographic and clinical characteristics in both the treatment and control groups . Overall physical performance , gait speed , measures of endurance and strength , and levels of physical activity improved in the treatment group compared to the control group ( p < .05 ) . Measures of autonomous regulation such as identified regulation , and measures of depression and QOL improved significantly in the treatment group compared with the control group ( p < .05 ) . Across the groups , improvement in intrinsic regulation and QOL correlated with an improvement in physical function ( p < .05 ) . CONCLUSION Our findings suggest that a physical activity counseling program grounded in SDT can improve physical function , autonomous motivation , depression , and QOL in HOA with functional limitations . ( PsycINFO Data base Purpose : Highly active antiretroviral therapy has significantly extended survival of human immunodeficiency virus ( HIV ) infected patients . These drugs suppress replication of HIV but at the same time , have many physical and mental side effects which may affect daily activities of the patients . The present study assessed if moderate intensity exercise program helped in enhancing the physical fitness and quality of life ( QoL ) in HIV positive females which may reduce the comorbidities associated with the disease and medications . Aim and Objectives : The aim of this study is to study the effects of moderate intensity physical training on physical fitness parameters and QoL in HIV positive females . Methodology : Post IEC approval , a r and omized control , single-blinded , parallel group trial was conducted on 55 females ( 20 experimental HIV , 20 control HIV , 15 control normal ) matching the selection criteria . Post informed consent , their muscular endurance , flexibility , aerobic capacity , and QoL was assessed . Moderate intensity physical exercises were given to experimental HIV and control normal 5 days/week for 8 weeks and subjects were reassessed for above parameters . Intragroup analysis was performed using paired t-test while inter-group was by one-way ANOVA with alpha set at ≤0.05 . Results : Moderate-intensity exercises improved muscular endurance ( P < 0.05 ) , flexibility ( P < 0.05 ) , and aerobic capacity ( P < 0.05)in experimental HIV and control normal group as compared to control HIV group . QoL in experimental HIV showed improvement in all the domains . Conclusion : Moderate-intensity exercises help improve the physical fitness as well as enhance the QoL in HIV positive females The primary purpose of this investigation was to determine the impact of altering the set structure during an 8-week resistance training program on anthropometric , hormonal , and strength power characteristics . Thirty female volleyball players were recruited for participation and then r and omly assigned to 1 of 3 resistance training groups : ( i ) cluster sets ( CRT ; n = 10 ) , ( ii ) traditional sets ( TRT ; n = 10 ) , or ( iii ) control ( CON ; n = 10 ) . All athletes were evaluated for thigh and arm circumference , vertical jump , 20-m sprint , 4 × 9-m shuttle-run , 1-repetition maximum ( 1RM ) back squat , bench press , military press , and deadlift prior to and after an 8-week periodized training intervention . Blood sample s were taken before and after the 8-week training period to evaluate resting testosterone , cortisol , and insulin-like growth factor 1 responses to the training period . After 8 weeks of training the CRT group displayed a small but significant improvement in vertical jump ( CRT : effect size ( ES ) = 038 , 7.1 % ) performance when compared with the TRT group ( ES = 0.34 , 5.6 % ) . Both the CRT and TRT training interventions result ed in very large increases in the 1RM squat ( CRT : 8.4 % ± 1.2 % ; TRT : 7.3 % ± 0.6 % ) , bench press ( CRT : 8.3 % ± 2.0 % ; TRT : 8.7 % ± 1.9 % ) , military press ( CRT : 5.7 % ± 1.2 % ; TRT : 5.5 % ± 1.6 % ) , and deadlift ( CRT : 8.2 % ± 1.6 % ; TRT : 8.3 % ± 2.2 % ) . There were no significant differences in 20-m sprint or 4 × 9-m shuttle run times between the CRT , TRT , and CON groups . These results suggest that cluster sets allow for greater improvements in vertical jump performance and equal improvements in strength gains to those seen with traditional sets HIV/AIDS and its treatment often alter body composition and result in poorer physical functioning . The aim of this study was to determine the effects of a moderate-intensity exercise program on body composition and the hormones and cytokines associated with adverse health outcomes . HIV-infected males ( N = 111 ) were r and omized to an exercise group ( EX ) who completed 6 weeks of moderate-intensity exercise training , or to a nonintervention control group ( CON ) . In pre- and postintervention , body composition was estimated via DXA , peak strength was assessed , and resting blood sample s were obtained . There was a decrease in salivary cortisol at wake ( P = 0.025 ) in the EX and a trend ( P = 0.07 ) for a decrease 1 hour after waking . The EX had a significant increase in lean tissue mass ( LTM ) ( P < 0.001 ) following the intervention . Those in the EX below median body fat ( 20 % ) increased LTM ( P = 0.014 ) only , while those above 20 % decreased fat mass ( P = 0.02 ) , total fat ( N = 0.009 ) , and trunk fat ( P = 0.001 ) , while also increasing LTM ( P = 0.027 ) . Peak strength increased between 14 % and 28 % on all exercises in the EX group . These data indicate that 6 weeks of moderate-intensity exercise training can decrease salivary cortisol levels , improve physical performance , and improve body composition in HIV-infected men OBJECTIVES : Human Immunodeficiency Virus ( HIV ) infection worsens the frailty of elderly people , compromising their quality of life . In this study we prospect ively evaluated eleven patients living with HIV and 21 controls older than 60 years and without prior regular physical activity , who engaged in a one-year progressive resistance exercise program to compare its effects on muscular strength , physical fitness and body composition . METHODS : Exercises for major muscular groups were performed 2 times/week , under professional supervision . Strength increase was evaluated bimonthly , while body composition , lipid and glycaemic profiles ( only of those living with HIV ) and physical fitness were evaluated before and after the one-year training . RESULTS : The participants living with HIV were lighter , had smaller Body Mass Index and were initially much weaker than controls . However , their strength increased more ( 1.52 - 2.33 times the baseline values for those living with HIV x 1.21 - 1.48 times for controls , p<0.01 ) , nullifying the differences initially seen . These effects were seen independently of gender , age or baseline physical activity . In addition , those living with HIV improved their fasting glucose levels and showed a tendency to improve their lipids after the one year training program . These effects were slightly more pronounced among those not using protease inhibitors , although not significantly . CONCLUSIONS : Resistance exercise safely increased the strength of older patients living with HIV adults , allowing them to achieve performance levels observed among otherwise healthy controls . These findings favor the recommendation of resistance exercise for elderly adults living with HIV adults Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome ( AIDS ) wasting syndrome ( AWS ) . Testosterone and exercise increase muscle mass in men with AWS , with unclear effects on muscle composition . We examined muscle composition in 54 eugonadal men with AWS who were r and omized to 1 ) testosterone ( 200 mg i m weekly ) or placebo and simultaneously to 2 ) resistance training or no training in a 2 x 2 factorial design . At baseline and after 12 wk , we performed assessment s of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition . Leaner muscle has greater attenuation . Baseline muscle attenuation correlated inversely with whole body fat mass ( r = -0.52 , P = 0.0001 ) . This relationship persisted in a model including age , body mass index , testosterone level , viral load , lean body mass , and thigh muscle cross-sectional area ( P = 0.02 ) . Testosterone ( P = 0.03 ) and training ( P = 0.03 ) increased muscle attenuation . These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training . Anabolic therapy in these patients increases muscle leanness BACKGROUND Women infected with human immunodeficiency virus ( HIV ) increasingly demonstrate abnormalities in fat distribution and metabolism ; however , the effects of a home-based exercise regimen in this group have not been investigated . METHODS We conducted a 16-week r and omized intervention study of a supervised home-based progressive resistance training and aerobic exercise program in 40 HIV-infected women with increased waist-hip ratio and self-reported fat redistribution . Cross-sectional muscle area and muscle attenuation were measured by computed tomography . Cardiorespiratory fitness was determined by calculated maximum oxygen consumption ( VO2max ) and strength by 1-repetition maximum . RESULTS Cardiorespiratory fitness ( VO2max ) was markedly lower at baseline ( median [ 95 % confidence interval ] , 15.4 [ 8.3 - 25.2 ] mL x kg(-1 ) x min(-1 ) ) than reported values for healthy female subjects ( 26 - 35 mL x kg(-1 ) x min(-1 ) ) . Subjects r and omized to exercise had significant improvement in mean + /- SEM VO2max ( 1.5 + /- 0.8 vs -2.5 + /- 1.6 mL x kg(-1 ) x min(-1 ) ; P<.001 ) and endurance ( 1.0 + /- 0.3 vs -0.6 + /- 0.3 minute ; P<.001 ) . Strength increased at the knee extensors , pectoralis , knee flexors , shoulder abductors , ankle plantar flexors , and elbow flexors ( all P<.001 ) . Total muscle area ( 6 + /- 1 vs 2 + /- 1 cm2 ; P = .02 ) and attenuation ( 2 + /- 1 vs -1 + /- 1 Hounsfield unit ; P = .03 ) increased in the exercise group . No significant difference was seen in lipid levels , blood pressure , or abdominal visceral fat between the groups , but subjects r and omized to exercise reported improved energy and appearance . CONCLUSIONS A 16-week , supervised , home-based exercise regimen improved measures of physical fitness in HIV-infected women . The effects on strength were most significant , but improvements in cardiorespiratory fitness , endurance , and body composition were also seen Although HIV-I infection rates peaked in the 1980s in the United States , advanced stage HIV disease will grow by about 40 % in the next 40 years . This fact has signaled the need for intervention strategies that go beyond primary prevention and into treatment of the complications associated with this chronic disease . Recently , the role of exercise in reversing the wasting process experienced by individuals with HIV-1 has received much needed attention . The purpose of this study was to examine the independent contributions of a 12-week aerobic or resistance weight training exercise regimen in improving body composition , muscle strength , and cardiovascular fitness in an HT V-l population . Participants for this study ( N = 33 ) were r and omly assigned to an aerobic exercise training group , a resistance weight training group , or a stretching/flexibility control group . Measures of body composition , muscular strength , and cardiovascular fitness were assessed both prior to and following completion of the intervention . In general , the results revealed significant improvements in the amount of lean muscle tissue , upper and lower body muscular strength , and predicted V02max for exercise participants , whereas control participants experienced declines in all physiological measures . Based on these findings , it is suggested that exercise may be one complimentary therapeutic modality capable of combating the wasting process associated with advanced HIV-1 infection OBJECTIVE To assess the impact of a multidisciplinary lifestyle intervention on cardiovascular risk and carotid intima-media thickness ( c-IMT ) in HIV-infected patients with Framingham scores ( FS ) > 10 % . DESIGN R and omized pilot study ; follow-up 36 months . METHODS Virologically suppressed adult HIV-1-infected patients with FS > 10 % were r and omized 1:1 to the intervention group ( multidisciplinary lifestyle intervention ) or control group ( routine care ) . At baseline and months 12 , 24 and 36 , lipid parameters were analyzed and carotid ultrasound was performed to determine c-IMT and presence of plaques . Biomarkers were measured at baseline and month 36 . The primary endpoints were lipid and FS changes at 36 months . RESULTS Fifty-four patients were included , 27 in each arm . Median age was 50.5 years , all patients but one were men , and FS was 16.5 % . Relative to controls , total and LDL cholesterol had significantly decreased in the intervention group at 24 months ( p = 0.039 , p = 0.011 , respectively ) . However , no differences between groups were found at month 36 in lipid variables , neither in FS . Tobacco use decreased in the intervention group ( p = 0.031 ) . At baseline , 74.5 % of patients had sub clinical atherosclerosis , and at month 36 , we observed a progression in c-IMT that was greater in the intervention group ( p = 0.030 ) . D-dimer increased ( p = 0.027 ) and soluble intercellular adhesion molecule-1 decreased ( p = 0.018 ) at 36 months . CONCLUSIONS In this cohort of HIV-infected patients with FS>10 % and a high percentage of sub clinical atherosclerosis , a multidisciplinary lifestyle intervention result ed in a slight improvement in some cardiovascular risk factors and the FS during the first 2 years , but did not prevent c-IMT progression This nonplacebo-controlled , open label , r and omized study was conducted to test the hypotheses that pharmacological doses of n and rolone decanoate would increase lean body tissue , muscle mass , and strength in immunodeficient human immunodeficiency virus-infected men , and that these effects would be enhanced with progressive resistance training ( PRT ) . Thirty human immunodeficiency virus-positive men with fewer than 400 CD4 lymphocytes/mm3 were r and omly assigned to receive weekly injections of n and rolone alone or in combination with supervised PRT at 80 % of the one-repetition maximum three times weekly for 12 weeks . Total body weight increased significantly in both groups ( 3.2 + /- 2.7 and 4.0 + /- 2.0 kg , respectively ; P < 0.001 ) , with increases due primarily to augmentation of lean tissue . Lean body mass determined by dual energy x-ray absorptiometry increased significantly more in the PRT group ( 3.9 + /- 2.3 vs. 5.2 + /- 5.7 kg , respectively ; P = 0.03 ) . Body cell mass by bioelectrical impedance analysis increased significantly ( P < 0.001 ) in both groups ( 2.6 + /- 1.0 vs. 2.9 + /- 0.8 kg ) , but to a similar magnitude ( P = NS ) . Significant increases in cross-sectional area by magnetic resonance imaging of total thigh muscles ( 1538 + /- 767 and 1480 + /- 532 mm2 ) , quadriceps ( 705 + /- 365 and 717 + /- 288 mm2 ) , and hamstrings ( 842 + /- 409 and 771 + /- 295 mm2 ) occurred with both treatment strategies ( P < 0.001 for the three muscle areas ) ; these increases were similar in both groups ( P = NS ) . By the one-repetition method , strength increased in both upper and lower body exercises , with gains ranging from 10.3 - 31 % in the n and rolone group and from 14.4 - 53.0 % in the PRT group ( P < 0.006 with one exception ) . Gains in strength were of significantly greater magnitude in the PRT group ( P < or = 0.005 for all comparisons ) , even after correction for lean body mass . Thus , pharmacological doses of n and rolone decanoate yielded significant gains in total weight , lean body mass , body cell mass , muscle size , and strength . The increases in lean body mass and muscular strength were significantly augmented with PRT 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 . Fregni F , Imamura M , Chien HF , Lew HL , Boggio P , Kaptchuk TJ , Riberto M , Hsing WT , Battistella LR , Furlan A : Challenges and recommendations for placebo controls in r and omized trials in physical and rehabilitation medicine : A report of the International Placebo Symposium Working Group . Compared with other specialties , the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and research ers in the scientific community . One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments . The best way to change this disadvantage is through a well conducted clinical research , such as st and ard placebo- or sham-controlled r and omized clinical trials . Therefore , having placebo groups in clinical trials is essential to improve the level of evidence -based practice in physical and rehabilitation medicine that ultimately translates to better clinical care . To address the challenges for the use of placebo in physical and rehabilitation medicine and r and omized clinical trials and to create useful recommendations , we convened a working group during the inaugural International Symposium in Placebo ( February 2009 , in Sao Paulo , Brazil ) in which the following topics were discussed : ( 1 ) current status of r and omized clinical trials in physical and rehabilitation medicine , ( 2 ) challenges for the use of placebo in physical and rehabilitation medicine , ( 3 ) bioethics , ( 4 ) use of placebo in acupuncture trials and for the treatment of low-back pain , ( 5 ) mechanisms of placebo , and ( 6 ) insights from other specialties . The current article represents the consensus report from the working group Abstract The purpose of this study is to analyse the effect of 12 weeks of non-linear resistance training ( NLRT ) on anthropometry , muscle strength and inflammatory biomarkers in persons infected with human immunodeficiency virus ( PIHIV ) . Thirty previously sedentary PIHIVs were r and omized into the NLRT ( n = 15 ) and control ( CON , n = 15 ) groups . NLRT group were su bmi tted to 12 weeks of training , whereas the CON group maintained their daily habits . At baseline and after 12 weeks , both groups underwent anthropometric evaluations and blood sampling for the analysis of inflammatory biomarkers . Analysis of covariance using preintervention values as covariate was performed to determine the effects of exercise on anthropometry , muscle strength , cytokines levels and T cells . Significance was set at p < 0.05 . After 12 weeks of intervention , there was a decrease in subcutaneous body fat ( p < .0001 ) , neck , abdomen and waist circumferences ( p < .05 ) , waist-to-hip ratio ( p = .009 ) , blood levels of interleukin (IL)-1β ( p = .029 ) , IL-6 ( p = .005 ) , IL-8 ( p = .010 ) , and tumour necrosis factor (TNF)-α ( p = .001 ) and an increase in muscle strength ( p < .0001 ) , IL-10 levels ( p = .030 ) and CD4 + ( p = .004 ) and CD8 + ( p < .0001 ) counts in the NLRT compared to CON group . Twelve weeks of NLRT promoted positive changes in the body fat , body circumferences , muscular strength and inflammatory profile in PIHIV Objective : To compare ox and rolone ( OX ) or strength training with nutrition alone ( NA ) for AIDS wasting . Subjects : Fifty patients with AIDS ; 47 completing the study . Interventions : R and omization to ( 1 ) NA with placebo pills , ( 2 ) nutrition with 10 mg of OX administered orally twice a day , or ( 3 ) nutrition with progressive resistance training ( PRT ) for 12 weeks . Main Outcome Measures : Midthigh cross-sectional muscle area ( CSMA ) , physical functioning ( PF ) , costs , and cost-effectiveness in dollars/ quality -adjusted life-years ( $ /QALYs ) . Results : The OX and PRT subjects had increases in CSMA ( 7.0 % ± 2.5 % , P = 0.01 ; 5.0 % ± 2.0 % , P = 0.04 , respectively ) , although these increases did not differ significantly from the NA arm ( NA : 1.0 % ± 1.0 % ; OX vs. NA : P = 0.09 ; PRT vs. NA : P = 0.26 ) . Only PRT caused significant improvements in PF ( mean ± SE : 10.4 ± 3.8 points on a 100-point scale ) and 7 measures of strength ( P values : 0.04 to < 0.001 ) . There were no overall differences between groups in PF change . Among patients with impaired baseline PF , however , OX was significantly less effective than NA and PRT was significantly better than NA . All treatments led to increases in protein intake and performance ; NA and PRT also increased caloric intake . The institutional costs per subject in this trial were $ 983 for NA , $ 3772 for OX , and $ 3189 for PRT . At a community-based level of intensity , the institutional costs per QALY were $ 45,000 ( range : $ 42,000-$64,000 ) for NA , $ 147,000 ( range : $ 147,000-$163,000 ) for OX , and $ 31,000 ( range : $ 21,000-$44,000 ) for PRT . Conclusions : OX and PRT induce similar improvements in body composition , but PRT improves quality of life more than nutrition or OX , particularly among patients with impaired PF . PRT was the most cost-effective intervention , and OX was the least cost-effective intervention BACKGROUND Substantial loss of muscle mass occurs among men with AIDS wasting . OBJECTIVE To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting . DESIGN R and omized , controlled trial . SETTING University hospital . PATIENTS 54 eugonadal men with AIDS wasting ( weight < 90 % ideal body weight or weight loss > 10 % ) . INTERVENTION In a 2 x 2 factorial design , patients were assigned to receive testosterone enanthate ( 200 mg/wk ) or placebo injections and progressive resistance training ( three times weekly ) or no training for 12 weeks . MEASUREMENTS Cross-sectional muscle area and other indices of muscle mass . RESULTS Cross-sectional muscle area increased in response to training compared with nontraining ( change in arm muscle mass , 499 + /- 349 mm2 vs. 206 + /- 264 mm2 [ P = 0.004 ] ; change in leg muscle mass , 1106 + /- 854 mm2 vs. 523 + /- 872 mm2 [ P = 0.045 ] ) and in response to testosterone therapy compared with placebo ( change in arm muscle mass , 512 + /- 371 mm2 vs. 194 + /- 215 mm2 [ P < 0.001 ] ; change in leg muscle mass , 1,236 + /- 881 mm2 vs. 399 + /- 729 mm2 [ P = 0.002 ] ) . Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo ( -0.03 + /- 0.13 mmol/L vs. 0.05 + /- 0.13 mmol/L [ -1 + /- 5 mg/dL vs. 2 + /- 5 mg/dL ] ; P= 0.011 ) and increased in response to training compared with nontraining ( 0.05 + /- 0.13 mmol/L vs. 0.00 + /- 0.16 mmol/L [ 2 + /- 5 mg/dL vs. 0 + /- 6 mg/dL ] ; P = 0.052 ) . CONCLUSIONS In contrast to anabolic therapies that may have adverse effects on metabolic variables , supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting ABSTRACT Distal symmetrical poly-neuropathy ( DSP ) is a neurological complication associated with HIV/AIDS and stavudine ( d4 T ) containing antiretroviral therapy . People with DSP experience pain , numbness and muscle weakness , which affect their quality of life ( QOL ) . The purpose of this study was to establish the effect of a progressive-resisted exercise ( PRE ) intervention on health-related quality of life ( HR-QOL ) in people living with HIV/AIDS-related DSP . An assessor-blinded r and omised controlled trial was conducted , with participants source d from 10 clinics with HIV services , the family care clinic at Wilkins Hospital and 2 large hospitals in Harare , Zimbabwe . A 12-week PRE intervention was conducted twice weekly for 80 participants , while the control group with 80 participants continued with usual daily activities . The main outcome variable was HR-QOL for which we controlled for demographic and clinical measures in generalised estimating equation population -averaged models . Data were summarised and analysed using an intention to treat analysis approach using the Stata v10 program . Mean age of participants was 42.2 years ( SD = 8.5 ) . While d4 T was used by 59 % ( n = 94 ) , an equal proportion of the participants also had moderate to severe neuropathy . PRE was found to significantly improve HR-QOL in the intervention group based on the mean difference between the intervention group mean change and the mean change in the control group ( F ratio 4.24 ; p = .04 ) . This study established that PREs have positive effects on HR-QOL for people living with HIV/AIDS-related DSP CONTEXT Fat redistribution , insulin resistance , and low- grade inflammation characterize HIV-infected patients with lipodystrophy . Currently , no effective therapies exist for the combined treatment of fat redistribution and insulin resistance . OBJECTIVE Our objective was to evaluate the effects of strength and endurance training on insulin sensitivity and fat distribution in HIV-infected patients with lipodystrophy . SUBJECTS AND METHODS Twenty sedentary HIV-infected men with lipodystrophy were r and omly assigned to supervised strength or endurance training three times a week for 16 wk . The primary endpoints were improved peripheral insulin sensitivity ( euglycemic-hyperinsulinemic clamp combined with isotope-tracer infusion ) and body fat composition ( dual-energy x-ray absorptiometry scan ) . Secondary endpoints included fasting lipids and inflammatory markers . RESULTS Insulin-mediated glucose uptake increased with both endurance training ( 55.7 + /- 11 to 63.0 + /- 11 micromol glucose/kg lean mass.min , P = 0.02 ) and strength training ( 49.0 + /- 12 to 57.8 + /- 18 micromol glucose/kg lean mass.min , P = 0.005 ) , irrespective of training modality ( P = 0.24 ) . Only strength training increased total lean mass 2.1 kg [ 95 % confidence interval ( CI ) , 0.8 - 3.3 ] , decreased total fat 3.3 kg ( 95 % CI , -4.6 to -2.0 ) , trunk fat 2.5 kg ( 95 % CI , -3.5 to -1.5 ) , and limb fat 0.75 kg ( 95 % CI , -1.1 to -0.4 ) . Strength training significantly decreased total and limb fat mass to a larger extent than endurance training ( P < 0.05 ) . Endurance training reduced total cholesterol , low-density lipoprotein cholesterol , free fatty acids , high-sensitivity C-reactive protein , IL-6 , IL-18 , and TNF-alpha and increased high-density lipoprotein cholesterol , whereas strength training decreased triglycerides , free fatty acids , and IL-18 and increased high-density lipoprotein cholesterol ( P < 0.05 for all measurements ) . CONCLUSION This study demonstrates that both strength and endurance training improve peripheral insulin sensitivity , whereas only strength training reduces total body fat in HIV-infected patients with lipodystrophy Objective To determine the effects of whey protein , resistance exercise , and combined protein and exercise treatment on body cell mass ( BCM ) , muscle strength , and quality of life ( QOL ) in HIV-infected women with reduced BCM . Design and setting Prospect i ve , r and omized , controlled trial at a university hospital in New York City . Methods A volunteer sample of 30 HIV-infected women were r and omized to whey protein ( PRO ) , progressive resistance exercise ( PRE ) , or combined treatment ( PRO – PRE ) for 14 weeks after a 6-week control period . The main outcome measures were body weight , BCM , skeletal muscle , fat mass , muscle strength , and QOL . Results There were no significant changes in BCM , strength , or QOL during the control period . PRO patients gained 3.6 kg ( P = 0.001 ) , and 2.5 kg fat ( P = 0.002 ) with no change in BCM ( 0.5 kg;P = 0.07 ) or skeletal muscle ( 0.6 kg;P = 0.12 ) . The PRE group increased BCM ( 0.74 kg;P = 0.03 ) and skeletal muscle ( 1.2 kg;P < 0.001 ) and decreased fat ( 1.7 kg;P = 0.02 ) . PRO – PRE increased BCM ( 0.61 kg;P = 0.01 ) without change in skeletal muscle ( 0.6 kg;P = 0.30 ) . Strength increased for both exercise groups ( range , 40.6–95.3%;P < 0.001 ) . The QOL physical activity score improved for PRE ( P = 0.02 ) and worsened for PRO ( P = 0.01 ) . Conclusions Resistance exercise significantly increased BCM , muscle mass , muscle strength , and QOL in HIV-infected women with reduced BCM . Whey protein had little effect on BCM accrual . Combined protein and exercise did not increase BCM in excess of gains achieved by exercise alone The impact of aerobic exercise training as a buffer of the affective distress and immune decrements which accompany the notification of HIV-1 antibody status in an AIDS risk group was studied . Fifty asymptomatic gay males with a pretraining fitness level of average or below ( determined by predicted VO2 max ) were r and omly assigned to either an aerobic exercise training program or a no-contact control condition . After five weeks of training , at a point 72 hours before serostatus notification , psychometric , fitness and immunologic data were collected on all subjects . Psychometric and immunologic measures were again collected one-week postnotification . Seropositive controls showed significant increases in anxiety and depression , as well as decrements in natural killer cell number following notification whereas , seropositive exercisers showed no similar changes and in fact , resembled both seronegative groups . These findings suggest that concurrent changes in some affective and immunologic measures in response to an acute stressor might be attenuated by an experimentally manipulated aerobic exercise training intervention CONTEXT Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength . The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown . OBJECTIVE To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss . DESIGN AND SETTING Placebo-controlled , double-blind , r and omized clinical trial conducted from September 1995 to July 1998 at a general clinical research center . PARTICIPANTS Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L ( 349 ng/dL ) and weight loss of 5 % or more in the previous 6 months , 49 of whom completed the study . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : placebo , no exercise ( n = 14 ) ; testosterone enanthate ( 100 mg/wk intramuscularly ) , no exercise ( n = 17 ) ; placebo and exercise ( n = 15 ) ; or testosterone and exercise ( n = 15 ) . Treatment duration was 16 weeks . MAIN OUTCOME MEASURES Changes in muscle strength , body weight , thigh muscle volume , and lean body mass compared among the 4 treatment groups . RESULTS Body weight increased significantly by 2.6 kg ( P<.001 ) in men receiving testosterone alone and by 2.2 kg ( P = .02 ) in men who exercised alone but did not change in men receiving placebo alone ( -0.5 kg ; P = .55 ) or testosterone and exercise ( 0.7 kg ; P = .08 ) . Men treated with testosterone alone , exercise alone , or both experienced significant increases in maximum voluntary muscle strength in leg press ( range , 22%-30 % ) , leg curls ( range , 18%-36 % ) , bench press ( range , 19%-33 % ) , and latissimus pulls ( range , 17%-33 % ) . Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group . There was a greater increase in thigh muscle volume in men receiving testosterone alone ( mean change , 40 cm3 ; P<.001 vs zero change ) or exercise alone ( 62 cm3 ; P = .003 ) than in men receiving placebo alone ( 5 cm3 ; P = .70 ) . Average lean body mass increased by 2.3 kg ( P = .004 ) and 2.6 kg ( P<.001 ) , respectively , in men who received testosterone alone or testosterone and exercise but did not change in men receiving placebo alone ( 0.9 kg ; P = .21 ) . Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo . CONCLUSION Our data suggest that testosterone and resistance exercise promote gains in body weight , muscle mass , muscle strength , and lean body mass in HIV-infected men with weight loss and low testosterone levels . Testosterone and exercise together did not produce greater gains than either intervention alone Objective : To determine whether exercise training in combination with metformin improves cardiovascular risk indices and insulin in comparison to metformin alone among HIV-infected patients . Methods and design : We conducted a prospect i ve , r and omized , 3-month study of HIV patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution . Subjects received metformin alone or metformin and exercise training consisting of 1 h of aerobic and resistance training three times a week . Cardiovascular parameters , including blood pressure and endurance during sub-maximal stress testing , body composition , strength , insulin and other biochemical parameters were determined . Results : Thirty-seven patients were r and omized and 25 subjects completed the study . Subjects receiving exercise training and metformin demonstrated significant decreases in median waist-to-hip ratio [ −0.02 ( −0.06 , −0.01 ) ( median ( interquartile range ) versus −0.01 ( 0.03 , 0.02 ) , P = 0.026 ] , resting systolic [ −12 ( −20 , −4 ) versus 0 ( −11 , 11 ) , P = 0.012 ] and diastolic blood pressures [ −10 ( −14 , −8 ) versus 0 ( −7 , 8) , P = 0.001 ] , increased thigh muscle cross-sectional area [ 3 ( −3 , 12 ) versus −7 ( −11 , 0 ) , P = 0.015 ] , and improved exercise time [ 3 ( 0 , 4 ) versus 0 ( −1 , 1 ) , P = 0.045 ] compared with subjects receiving metformin alone . Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group ( P < 0.05 ) . Lipids and resting lactate did not change significantly between treatment groups . Conclusions : These data demonstrate that exercise training in combination with metformin significantly improves cardiovascular and biochemical parameters more than metformin alone in HIV-infected patients with fat redistribution and hyperinsulinemia . Combined treatment was safe , well tolerated and may be a useful strategy to decrease cardiovascular risk in this population Our primary aim was to study the effects of a 4-week preparatory resistance-training ( RT ) period followed by 12 weeks of 2 specific RT protocol s ( either hypertrophic-strength ( HS ) or strength-hypertrophy-power training ) on inflammation markers and the possible relationship of the changes in abdominal fat and lean mass to the changes in inflammation status . A total of 82 healthy men were included in the study . Maximal concentric leg press strength ( 1-repetition maximum ) , total body lean mass , total body and abdominal fat mass , circulating high-sensitivity C-reactive protein , interleukin-6 , interleukin-1 receptor antagonist ( IL-1ra ) , monocyte chemoattractant protein 1 ( MCP-1 ) , and selected adipocytokines ( resistin , adiponectin , and leptin ) concentrations were measured before and after 4 ( wk4 ) and 16 weeks ( wk16 ) of RT . After the initial phase of RT , on wk4 , abdominal and total fat mass as well as plasma leptin concentrations were significantly reduced ( p < 0.05 ) , whereas muscle mass , IL-1ra , resistin , and MCP-1 concentrations were significantly increased ( p < 0.05 ) . During specialized training phase , at wk16 , only HS led to further reduction in abdominal and total fat mass , resistin , and leptin ( p < 0.05 ) , whereas both training modes led to lower MCP-1 concentrations ( p < 0.05 ) . Abdominal fat mass and circulating leptin were reduced already after 4 weeks of RT . Simultaneously , circulating MCP-1 and resistin concentrations increased , possibly as markers of muscle adaptation and regeneration . The present findings also suggest that RT with hypertrophic focus is beneficial for further reductions in abdominal fat mass and to decrease circulating inflammatory markers |
10,393 | 31,060,573 | Higher prevalences of oral and anal sex were reported among population s at high-risk for sexually transmitted infections and HIV and university students and , in most studies , both behaviours were more commonly reported by males than females .
Heterosexual oral and anal sexual acts were associated with some high-risk behaviours such as inconsistent condom use and multiple sexual partners .
Conclusion Reported oral and anal sex between men and women are prevalent behaviours in sub-Saharan Africa . | Background Oral and anal sexual behaviours are increasingly reported among adolescents and adults reporting heterosexual sex in peer- review ed journals in high income countries , but less is known about these behaviours in low and middle-income countries , especially in sub-Saharan Africa .
The aim of this systematic review is to describe the prevalence of , and motivations for , oral and anal sex among adolescents and adults reporting heterosexual sex in sub-Saharan Africa . | BACKGROUND Female-initiated HIV-prevention options , such as microbicides , are urgently needed . We assessed Carraguard , a carrageenan-based compound developed by the Population Council , for its efficacy and long-term safety in prevention of HIV infection in women . METHODS We undertook a r and omised , placebo-controlled , double-blind trial in three South African sites in sexually-active , HIV-negative women , aged 16 years and older . 6202 participants , who were r and omly assigned by a block r and omisation scheme to Carraguard ( n=3103 ) or placebo ( methylcellulose [ n=3099 ] ) , were instructed to use one applicator of gel plus a condom during each vaginal sex act . Participants were followed up for up to 2 years . Visits every 3 months included testing for HIV presence and pregnancy , pelvic examinations , risk reduction counselling , and treatment for curable sexually transmitted infections and symptomatic vaginal infections . The primary outcome was time to HIV seroconversion . Analysis was in the efficacy population ( a subset of the intention-to-treat population , excluding participants for whom efficacy could not be assessed ) . This study is registered with Clinical Trials.gov , number NCT00213083 . FINDINGS For the primary outcome ( time to HIV seroconversion ) we analysed 3011 women in the Carraguard group and 2994 in the placebo group . HIV incidence was 3.3 per 100 woman-years ( 95 % CI 2.8 - 3.9 ) in the Carraguard group ( 134 events ) and 3.8 per 100 woman-years ( 95 % CI 3.2 - 4.4 ) in the placebo group ( 151 events ) , with no significant difference in the distribution of time to seroconversion ( p=0.30 ) . The covariate-adjusted hazard ratio was 0.87 ( 95 % CI 0.69 - 1.09 ) . Rates of self-reported gel use ( 96.2 % Carraguard , 95.9 % placebo ) and condom use ( 64.1 % in both groups ) at last sex acts were similar in both groups . On the basis of applicator testing , however , gel was estimated to have been used in only 42.1 % of sex acts , on average ( 41.1 % Carraguard , 43.1 % placebo ) . 1420 ( 23 % ) women in the intention-to-treat population had adverse events ( 713 Carraguard , 707 placebo ) , and 95 ( 2 % ) women had adverse events that were related to gel use ( 48 Carraguard , 47 placebo ) . Serious adverse events occurred in 72 ( 2 % ) women in the Carraguard group and 78 ( 3 % ) in the placebo group , only one of which was considered possibly related to gel use ( placebo group ) . INTERPRETATION This study did not show Carraguard 's efficacy in prevention of vaginal transmission of HIV . No safety concerns were recorded Introduction Since female learners in high schools in Cameroon fall within the age group hardest hit by HIV/AIDS , it is assumed that these learners might be exposed to sexual risk behaviours . However , little has been explored on the sexual risk behaviours of high school female learners in Cameroon . This study aim ed at examining the sexual risk behaviours of high school female learners in Mbonge subdivision of rural Cameroon . Methods A cross sectional design was adopted , using a self-administered question naire for data collection . Respondents were selected through disproportional stratified simple r and om sampling result ing in 210 female grade 10 to grade 12 learners from three participating high schools in Mbonge subdivision , Cameroon . Descriptive and inferential statistics were calculated using SPSS version 20 software program . Results Majority of the respondents , 54.0 % reported being sexually active , of whom only 39.8 % used condoms during first sex ; 49.5 % used condoms during last sex and 29.6 % used condoms consistently . Up to 32 % of the sexually active respondents had multiple sexual partners in the past one year before the study , while 9.3 % had multiple sexual partners during the study period . The mean age of first sex was 15.6 years . Lack of parental control , religion , academic profile , poverty , place of residence and perception of risk of HIV infection were the main factors significantly associated with sexual risk behaviours . Conclusion The findings indicate that sexual risk behaviours exist among high school female learners in Mbonge , Cameroon . There is need for campaigns and interventions to bring about sexual behaviour change BACKGROUND Underst and ing the signification of the word ' sex ' has implication s for both medical research and clinical practice . Little is known about how people of varying ages define sex and how situational qualifiers influence definitions across age groups . To our knowledge , this is the first study of a representative sample to assess attitudes about which sexual behaviours constitute having ' had sex ' and to examine possible mediating factors ( gender , age , giving/receiving stimulation , male ejaculation , female orgasm , condom use or brevity ) . METHODS A telephone survey of English-speaking residents of Indiana ( USA ) using r and om-digit-dialling produced a final sample of 204 men and 282 women ( n = 486 ) ranging in age from 18 to 96 years . Questions assessed the respondents ' attitudes on manual-genital ( MG ) , oral-genital ( OG ) , penile-vaginal intercourse ( PVI ) and penile-anal intercourse ( PAI ) behaviours . RESULTS There was no universal consensus on which behaviours constituted having ' had sex ' . More than 90 % responded ' yes ' to PVI but one in five responded ' no ' to PAI , three in 10 responded ' no ' to OG and about half endorsed MG . Fewer endorsed PVI with no male ejaculation ( 89.1 % ) compared with PVI without a qualifier ( 94.8 % , P < 0.001 ) . MG was endorsed more often when received ( 48.1 % ) than given ( 44.9 % , P < 0.001 ) . Among men , the oldest and youngest age groups were significantly less likely to believe certain behaviours constituted having ' had sex ' . CONCLUSIONS These findings highlight the need to use behaviour-specific terminology in sexual history taking , sex research , sexual health promotion and sex education . Research ers , educators and medical practitioners should exercise caution and not assume that their own definitions of having ' had sex ' are shared by their research participants or patients Background HIV acquisition in pregnancy and breastfeeding contributes significantly toward pediatric HIV infection . However , little is known about how sexual behavior changes during pregnancy and postpartum periods which will help develop targeted HIV prevention and transmission interventions , including pre-exposure prophylaxis ( PrEP ) . Methods Cross-sectional study in HIV-infected and uninfected pregnant and postpartum women in Cape Town , South Africa . Interviewers collected survey data on demographic , sexual behaviors , and alcohol use among pregnant and post-partum women . We report descriptive results of sexual behavior by trimester and postpartum period , and results of multivariable logistic regression stratified by pregnancy status . Results We enrolled 377 pregnant and postpartum women ( 56 % pregnant , 40 % HIV-infected ) . During pregnancy , 98 % of women reported vaginal sex ( 8 % anal sex , 44 % oral sex ) vs. 35 % and 88 % during the periods 0–6 and 7–12 months postpartum , respectively ( p<0.05 ) . More pregnant women reported having > 1 partner in the past 12-months compared to postpartum women ( 18 % vs. 13 % , respectively , p<0.05 ) . Sex frequency varied by trimester with greatest mean sex acts occurring during first trimester and > 6-months postpartum ( 13 mean sex acts in first trimester ; 17 mean sex acts > 6-months postpartum ) . Pregnant women had increased odds of reporting condomless sex at last sex ( aOR = 2.96;95%CI = 1.84–4.78 ) and ever having condomless sex in past 3-months ( aOR = 2.65;95%CI = 1.30–5.44 ) adjusting for age , HIV status , and sex frequency compared to postpartum women . Conclusion We identified that sexual behaviors and risk behaviors were high and changing during pregnancy and postpartum periods , presenting challenges to primary and secondary HIV prevention efforts , including PrEP delivery to pregnant and breastfeeding women Background Sex work has shifted from brothels to entertainment establishments ( EEs ) in Asia . Men who patronise EEs could act as a bridging population for human immunodeficiency virus ( HIV ) and sexually transmitted infection ( STI ) transmission through unprotected sex with the female EE workers to their spouses and regular partners . The aim of this study was to compare the prevalence and factors associated with risky sexual behaviours among the heterosexual men who patronised the EEs and brothels in Singapore . Methods This was a cross-sectional survey involving 569 heterosexual men ( 297 recruited from brothels and 272 from EEs ) . A 2-stage sampling involving proportional stratified r and om sampling of the brothels and EEs , followed by time location sampling of the men , was conducted . For multivariable analysis , we used a mixed effects logistic model with backward elimination to account for clustering by venue and to obtain the adjusted odds ratio ( aOR ) for the association of various factors with consistent condom use in vaginal and oral sex respectively . Results Men who patronised EEs were younger , more likely to be single , more highly-educated and comprised more professionals compared to the brothel group . On multivariable analysis , consistent condom use for vaginal sex decreased at the EE setting ( aOR 0.64 ; 95 % CI : 0.42 –0.97 ) and with alcohol use before sex ( aOR 0.67 ; 95 % CI : 0.46 – 0.98 ) and increased with perceived high risk of getting HIV/STIs from partner ( aOR 2.08 ; 95 % CI : 1.30 – 3.32 ) and partner ’s request for condom use ( aOR 5.48 ; 95 % CI : 1.20 – 25.11 ) . For consistent condom use with oral sex , this decreased at the EE setting ( aOR 0.64 ; 95 % CI : 0.39 – 0.98 ) and with alcohol use before sex ( aOR 0.50 ; 95 % CI : 0.31 – 0.81 ) and increased with partner ’s request for condom use ( aOR 5.19 ; 95 % CI : 1.38 – 19.57 ) . Conclusions Men who patronised EEs practised risker sexual behaviours compared to the brothel group . Priority should be given for intervention programmes to target men who patronise EEs , which could involve the female EE workers , the EE owners as well as the managers for effective HIV/STI prevention Vaginal Gel Versus HIV HIV prevention technologies for women are urgently needed , especially in sub-Saharan Africa where young women bear the greatest burden of the HIV epidemic . Abdool Karim et al. ( p. 1168 ; published online 19 July ) present the results of the CAPRISA 004 r and omized control trial . The nearly 3-year-long trial , conducted in urban and rural South African women , tested the efficacy of a vaginal gel containing the antiretroviral drug tenofovir in preventing HIV infection . The dosing strategy required application of the gel both before and after coitus , and with this regime HIV infection was reduced by approximately 39 % overall , by 54 % in women with high adherence to the protocol , and with no increase in overall adverse event rates . Tenofovir in a vaginal gel formulation shows significant protection against HIV infection in a r and omized control trial . The Centre for the AIDS Program of Research in South Africa ( CAPRISA ) 004 trial assessed the effectiveness and safety of a 1 % vaginal gel formulation of tenofovir , a nucleotide reverse transcriptase inhibitor , for the prevention of HIV acquisition in women . A double-blind , r and omized controlled trial was conducted comparing tenofovir gel ( n = 445 women ) with placebo gel ( n = 444 women ) in sexually active , HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal , South Africa . HIV serostatus , safety , sexual behavior , and gel and condom use were assessed at monthly follow-up visits for 30 months . HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years ( person time of study observation ) ( 38 out of 680.6 women-years ) compared with 9.1 per 100 women-years ( 60 out of 660.7 women-years ) in the placebo gel arm ( incidence rate ratio = 0.61 ; P = 0.017 ) . In high adherers ( gel adherence > 80 % ) , HIV incidence was 54 % lower ( P = 0.025 ) in the tenofovir gel arm . In intermediate adherers ( gel adherence 50 to 80 % ) and low adherers ( gel adherence < 50 % ) , the HIV incidence reduction was 38 and 28 % , respectively . Tenofovir gel reduced HIV acquisition by an estimated 39 % overall , and by 54 % in women with high gel adherence . No increase in the overall adverse event rates was observed . There were no changes in viral load and no tenofovir resistance in HIV seroconverters . Tenofovir gel could potentially fill an important HIV prevention gap , especially for women unable to successfully negotiate mutual monogamy or condom use Objective The authors analysed data from female sex workers screened prior to participation in a microbicide trial to examine the association between prevalent vaginal flora abnormalities and HIV infection , with special emphasis on the role of the intermediate vaginal flora ( IVF ) in this association . Methods Data from the Kampala , Cotonou , Chennai and Mudhol/Jamkh and i sites were analysed . Participants were interviewed and provided blood for HIV and syphilis antibody testing , genital sample s for the diagnosis of vaginal flora abnormalities ( using Nugent score ) and other reproductive tract infections . Log-binomial regression was used to estimate the HIV prevalence ratio ( PR ) in relation to IVF and bacterial vaginosis ( BV ) . Results Among 1367 women , BV , IVF and HIV prevalences were 47.6 % ( 95 % CI=45.0 % to 50.3 % ) , 19.2 % ( 95 % CI=17.1 % to 21.2 % ) and 27.0 % ( 95 % CI=24.6 % to 29.3 % ) , respectively . In multivariate analysis , adjusting for study site , age , years of education , occupation , female sterilisation , oral sex , past history of sexually transmitted infection , gonorrhoea and c and idiasis , IVF was significantly associated with HIV infection with a PR similar to that of BV ( adjusted PR=1.56 ( 95 % CI=1.22 to 1.98 ) and 1.48 ( 95 % CI=1.20 to 1.84 ) , respectively ) . Conclusions Though the cross-sectional design of the study precludes directional interpretation of the findings , the data do suggest that IVF may be as important as BV in HIV acquisition . The authors recommend prospect i ve research to better underst and the association between IVF and HIV acquisition Introduction The influence of media portrayals of sexual attitudes and normative expectations of young people at a critical developmental stage is of public health concern . Objectives To examine the role of mass media and Internet utilization in shaping the sexual health attitudes and behaviors of young undergraduates in Osogbo metropolis , Osun State , Nigeria . Material s and methods In a descriptive cross-sectional study , 400 undergraduates were selected using a multistage r and om sampling technique . Four hundred and fifty pretested , semistructured question naires were distributed ; of these , 400 were returned properly filled . Data were analyzed using SPSS statistical software version 16 . Results Mean age of respondents ± st and ard deviation was 23.6±2.99 years . Most were aware of the various forms of mass media ( > 95 % ) . Most ( 64.0 % ) respondents spent 1–5 hours watching television , daily , and most used the Internet often . About 38.3 % and 24.2 % of respondents used the Internet and radio/television , respectively , as sources of information on sexual issues . Most respondents used the Internet for school assignments ( 83.0 % , n=332 ) , electronic mail ( 89.0 % , n=356 ) , and for accessing sexually explicit material s ( 74.5 % , n=298 ) . Most of the respondents ( 73.5 % ) opined that the Internet has a bad influence on youths ’ sexual behavior , although accessing the Internet for sexual material or movies was acceptable to 25.3 % of them . Of the 226 respondents who had ever had sex , 226 ( 100 % ) , 37 ( 16.4 % ) , 31 ( 13.7 % ) , and 10 ( 4.4 % ) practice d coitus , oral sex , masturbation , and anal sex , respectively ; 122 ( 54.0 % ) always used condoms , whereas 90 ( 40.0 % ) never used condoms during sexual activity ; 33 ( 14.6 % ) had had sex with commercial sex workers . Further analysis showed that those who were yet to marry ( single ) were less likely to be sexually experienced than those who were married ( adjusted odds ratio [ AOR ] = 0.075 , 95 % confidence interval [ CI ] = 0.008–0.679 ) , and those who said accessing the Internet for sexual material is not acceptable to them were also less likely to be sexually experienced than those to whom it was acceptable ( AOR = 0.043 , 95 % CI = 0.016–0.122 ) . Predictors of having multiple sexual partners include the sex of the respondent and the frequency of Internet use , with females ( AOR = 0.308 , 95 % CI = 0.113–0.843 ) and those who rarely use the Internet less likely to have multiple sexual partners . Conclusion We conclude that uncontrolled exposure to mass media and Internet could negatively influence the sexual patterns and behavior of youths Introduction Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies . Antiretroviral pre-exposure prophylaxis is a promising prevention approach ; however , clinical trials among young women using daily or coitally-dependent products have found low adherence . Antiretroviral-containing vaginal microbicide rings , which release medication over a month or longer , may reduce these adherence challenges . Methods ASPIRE ( A Study to Prevent Infection with a Ring for Extended Use ) is a phase III , r and omized , double-blind , placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection . We describe the baseline characteristics of African women enrolled in the ASPIRE trial . Results Between August 2012 and June 2014 , 5516 women were screened and 2629 HIV-1 seronegative women between 18–45 years of age were enrolled from 15 research sites in Malawi , South Africa , Ug and a , and Zimbabwe . The median age was 26 years ( IQR 22–31 ) and the majority ( 59 % ) were unmarried . Nearly 100 % of participants reported having a primary sex partner in the prior three months but 43 % did not know the HIV-1 status of their primary partner ; 17 % reported additional concurrent partners . Nearly two-thirds ( 64 % ) reported having disclosed to primary partners about planned vaginal ring use in the trial . Sexually transmitted infections were prevalent : 12 % had Chlamydia trachomatis , 7 % Trichomonas vaginalis , 4 % Neisseria gonorrhoeae , and 1 % syphilis . Conclusions African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention Background Studies assessing risk of sexual behavior and disease are often plagued by questions about the reliability of self-reported sexual behavior . In this study , we evaluated the reliability of self-reported sexual history among urbanized women in a prospect i ve study of cervical HPV infections in Nigeria . Methods We examined test – retest reliability of sexual practice s using question naires administered at study entry and at follow-up visits . We used the root mean squared approach to calculate within-person coefficient of variation ( CVw ) and calculated the intra-class correlation coefficient ( ICC ) using two way , mixed effects models for continuous variables and ( κ^ ) statistics for discrete variables . To evaluate the potential predictors of reliability , we used linear regression and log binomial regression models for the continuous and categorical variables , respectively . Results We found that self-reported sexual history was generally reliable , with overall ICC ranging from 0.7 to 0.9 ; however , the reliability varied by nature of sexual behavior evaluated . Frequency reports of non-vaginal sex ( agreement = 63.9 % , 95 % CI : 47.5–77.6 % ) were more reliable than those of vaginal sex ( agreement = 59.1 % , 95 % CI : 55.2–62.8 % ) . Reports of time-invariant behaviors were also more reliable than frequency reports . The CVw for age at sexual debut was 10.7 ( 95 % CI : 10.6–10.7 ) compared with the CVw for lifetime number of vaginal sex partners , which was 35.2 ( 95 % CI : 35.1–35.3 ) . The test – retest interval was an important predictor of reliability of responses , with longer intervals result ing in increased inconsistency ( average change in unreliability for each 1 month increase = 0.04 , 95 % CI = 0.07–0.38 , p = 0.005 ) . Conclusion Our findings suggest that overall , the self-reported sexual history among urbanized Nigeran women is reliable Introduction Young women are at disproportionate risk of HIV infection in South Africa . Underst and ing risk behaviors and factors associated with ability to negotiate safe sex and condom use is likely to be key in curbing the spread of HIV . Traditionally prevention efforts have focused on creating behavioral changes by increasing knowledge about HIV/AIDS . Methods This was a cross-sectional analysis from a prospect i ve observational cohort study of 245 women at a high-risk of HIV infection in KwaZulu-Natal , South Africa . Results Participants demonstrated a high level of HIV/AIDS knowledge . Overall , 60.3 % of participants reported condom use . Reported condom use at last sexual encounter varied slightly by partner type ( 57.0 % with steady versus 64.4 % with casual partners ) , and self-perceived ability to choose to use a condom was significantly lower with steady partners compared to casual partners ( p<0.01 ) . In multivariate analysis , women who had high school education were more likely to use condoms at their last sex encounter compared to those with only primary school education ( RR of 1.36 ( 95 % Confidence Interval ( CI ) 1.06–1.75 ) and 1.46 ( 95 % CI 1.13–1.88 ) for grade s 8–10 and 11–12 , respectively ) . Those who used condoms as a contraceptive method were twice as likely to use condoms compared to women who did not report using them as a contraceptive method . Greater perceived ability to choose to use condoms was associated with higher self-reported condom use at last encounter , irrespective of partner type ( RR = 2.65 ( 95 % CI 2.15–32.5 ) . Discussion Self-perceived ability to use condoms , level of formal education and condom use as a contraceptive were all significantly associated with self-reported condom use at last sexual encounter . These findings suggest that that gender ine quality and access to formal education , as opposed to lack of HIV/AIDS knowledge , prevent safer sexual practice s in South Africa Summary Background Sexual behaviour and relationships are key components of wellbeing and are affected by social norms , attitudes , and health . We present data on sexual behaviours and attitudes in Britain ( Engl and , Scotl and , and Wales ) from the three National Surveys of Sexual Attitudes and Lifestyles ( Natsal ) . Methods We used a multistage , clustered , and stratified probability sample design . Within each of the 1727 sample d postcode sectors for Natsal-3 , 30 or 36 addresses were r and omly selected and then assigned to interviewers . To over sample individuals aged 16–34 years , we r and omly allocated addresses to either the core sample ( in which individuals aged 16–74 years were eligible ) or the boost sample ( in which only individuals aged 16–34 years were eligible ) . Interviewers visited all sample d addresses between Sept 6 , 2010 , and Aug 31 , 2012 , and r and omly selected one eligible individual from each household to be invited to participate . Participants completed the survey in their own homes through computer-assisted face-to-face interviews and self-interview . We analysed data from this survey , weighted to account for unequal selection probabilities and non-response to correct for differences in sex , age group , and region according to 2011 Census figures . We then compared data from participants aged 16–44 years from Natsal-1 ( 1990–91 ) , Natsal-2 ( 1999–2001 ) , and Natsal-3 . Findings Interviews were completed with 15 162 participants ( 6293 men , 8869 women ) from 26 274 eligible addresses ( 57·7 % ) . 82·1 % ( 95 % CI 81·0–83·1 % ) of men and 77·7 % ( 76·7–78·7 % ) of women reported at least one sexual partner of the opposite sex in the past year . The proportion generally decreased with age , as did the range of sexual practice s with partners of the opposite sex , especially in women . The increased sexual activity and diversity reported in Natsal-2 in individuals aged 16–44 years when compared with Natsal-1 has generally been sustained in Natsal-3 , but in men has generally not risen further . However , in women , the number of male sexual partners over the lifetime ( age-adjusted odds ratio 1·18 , 95 % CI 1·08–1·28 ) , proportion reporting ever having had a sexual experience with genital contact with another woman ( 1·69 , 1·43–2·00 ) , and proportion reporting at least one female sexual partner in the past 5 years ( 2·00 , 1·59–2·51 ) increased in Natsal-3 compared with Natsal-2 . While reported number of occasions of heterosexual intercourse in the past 4 weeks had reduced since Natsal-2 , we recorded an expansion of heterosexual repertoires — particularly in oral and anal sex — over time . Acceptance of same-sex partnerships and intolerance of non-exclusivity in marriage increased in men and women in Natsal-3 . Interpretation Sexual lifestyles in Britain have changed substantially in the past 60 years , with changes in behaviour seeming greater in women than men . The continuation of sexual activity into later life — albeit reduced in range and frequency — emphasises that attention to sexual health and wellbeing is needed throughout the life course . Funding Grants from the UK Medical Research Council and the Wellcome Trust , with support from the Economic and Social Research Council and the Department of Health Misreporting of adherence undermines detection of an association between product use and HIV infection in microbicide trials . This study investigates whether , in a placebo trial , audio computer-assisted self-interviewing ( ACASI ) produces more accurate reporting of adherence and sexual behavior than a face-to-face interview ( FTFI ) . At three South African clinics , 849 women were enrolled and instructed to use applicators filled with placebo gel ; participants were r and omly assigned to FTFI or ACASI . Behavioral reports were vali date d through two biomarkers that detect product usage and unprotected sex . For most behaviors , ACASI generated significantly higher reporting , although differences by interview mode appeared to diminish over time . ACASI participants were more likely to report having had sex without gel , but reported and tested applicators did not indicate greater honesty about gel insertion with ACASI . While comparisons of reported unprotected sex with the vali date d biomarker revealed more agreement with ACASI than with FTFI , differences were small Objectives : To determine prevalence of and risk factors for herpes simplex virus type 2 ( HSV-2 ) and HIV among women being screened for a r and omized , controlled trial of HSV suppressive therapy in northwestern Tanzania . Methods : Two thous and seven hundred nineteen female facility workers aged 16 to 35 were interviewed and underwent serological testing for HIV and HSV-2 . Factors associated with HSV-2 and HIV in women aged 16 to 24 were examined using logistic regression to estimate odds ratios ( OR ) and 95 % confidence intervals ( CI ) . Results : HSV-2 seroprevalence was 80 % , and HIV seroprevalence was 30 % . Among women aged 16 to 24 , both infections were significantly and independently associated with older age , being a bar worker , working at a truck stop , and having more lifetime sexual partners . HSV-2 infection was also associated with lower socioeconomic status , increased alcohol intake , younger age at first sex , inconsistent condom use , and vaginal douching . There was a strong association between the 2 infections after adjustment for other factors ( OR = 4.22 , 95 % CI : 2.6 to 6.9 ) . Conclusions : Female facility workers in northwestern Tanzania are vulnerable to HSV-2 and HIV infections . Programs design ed to increase safer sexual behavior and reduce alcohol use could be effective in reducing HSV-2 incidence and , in turn , HIV infection . This is a suitable population for an HSV suppressive therapy trial BACKGROUND In mature generalized human immunodeficiency virus ( HIV ) epidemics , as survival from accessing antiretroviral treatment ( ART ) increases , HIV prevalence data may be suboptimal and difficult to interpret without HIV incidence rates . OBJECTIVE To determine the HIV incidence rate among rural and urban women in KwaZulu-Natal , South Africa . METHODS We conducted a prospect i ve cohort study from March 2004 to May 2007 . Volunteers were recruited from a rural family-planning clinic and an urban clinic for sexually transmitted infections . Consenting , HIV-uninfected women aged 14 - 30 years were enrolled . Demographic , clinical , sexual and behavioural data were collected using st and ardized question naires with HIV risk reduction counselling and HIV testing . Pelvic examinations were completed at quarterly visits . RESULTS The HIV prevalence at screening was 35.7 % [ 95 % confidence interval ( CI ) 32.7 - 38.8 ] amongst rural women and 59.3 % ( 95 % CI 56.5 - 62.0 ) amongst urban women . A total of 594/2240 ( 26.5 % ) enrolled women contributed to 602 person-years ( PYs ) of follow-up . The median age was 22 years [ inter-quartile range 18 - 23 years ] . HIV incidence rate was 6.5/100 PY ( 95 % CI 4.4 - 9.2 ) amongst rural women and 6.4/100 PY ( 95 % CI 2.6 - 13.2 ) amongst urban women . HIV incidence rate of 17.2/100 PY ( 95 % CI 2.1 - 62.2 ) was highest amongst urban women < 20 years of age and 10.2/100 PY ( 95 % CI 4.1 - 20.9 ) amongst rural women ≥ 25 years of age . CONCLUSION HIV incidence rates are devastatingly high in young women in rural and urban KwaZulu-Natal , despite reports of stabilized HIV prevalence observed in current surveillance data . The diffuse nature of the HIV epidemic underscores the urgent need to enhance HIV prevention and treatment modalities BACKGROUND Nonoxynol-9 ( rINN , nonoxinol-9 ) is an over-the-counter spermicide that has in-vitro anti-HIV-1 activity . Results of studies of its effectiveness in prevention of HIV-1 infection in women have been inconclusive . We aim ed to assess effectiveness of this vaginal gel . METHODS We did a r and omised , placebo-controlled , triple-blinded , phase 2/3 trial with COL-1492 , a nonoxynol-9 vaginal gel , in 892 female sex workers in four countries : Benin , Côte d'Ivoire , South Africa , and Thail and . 449 women were r and omly allocated nonoxynol-9 and 443 placebo . Primary endpoint was incident HIV-1 infection . Secondary endpoints included Neisseria gonorrhoeae and Chlamydia trachomatis infections . Analysis was by intention to treat . FINDINGS 765 women were included in the primary analysis . HIV-1 frequency in nonoxynol-9 users was 59 ( 16 % ) of 376 compared with 45 ( 12 % ) [ corrected ] of 389 in placebo users ( 402.5 vs 435.0 woman-years ; hazard ratio adjusted for centre 1.5 ; 95 % CI 1.0 - 2.2 ; p=0.047 ) . 239 ( 32 % ) women reported use of a mean of more than 3.5 applicators per working day , and in these women , risk of HIV-1 infection in nonoxynol-9 users was almost twice that in placebo users ( hazard ratio 1.8 ; 95 % CI 1.0 - 3.2 ) . 516 ( 68 % ) women used the gel less frequently than 3.5 times a day , and in these , risk did not differ between the two treatments . No significant effect of nonoxynol-9 on N gonorrhoeae ( 1.2 ; 0.9 - 1.6 ) or C trachomatis ( 1.2 ; 0.8 - 1.6 ) infections was reported . INTERPRETATION This study did not show a protective effect of COL-1492 on HIV-1 transmission in high-risk women . Multiple use of nonoxynol-9 could cause toxic effects enhancing HIV-1 infection . This drug can no longer be deemed a potential HIV-1-prevention method . Assessment of other microbicides should continue A cross-sectional question naire survey was conducted among 892 r and omly selected pupils , aged 12 and above , attending 18 primary schools ( PS ) and five secondary schools ( SS ) in four communities of Mwanza Region in Tanzania . The goals were to assess the level of knowledge adolescents have about sexual and reproductive health ( SRH ) , to assess the magnitude of SRH problems and to help design appropriate interventions . Median age of respondents was 15 years ( range 12 - 20 years ) and 14 years ( range 12 - 19 years ) for PS boys and girls , respectively , and 19 years ( range 16 - 24 years ) and 17 years ( range 14 - 19 years ) for SS boys and girls . Eighty per cent of PS boys and 68 % of PS girls were already sexually active ; the corresponding figures were 89 % for SS boys and 48 % for SS girls . Vaginal sex was the most common first sexual act reported by SS pupils , but 40 % of PS pupils reported orogenital sex and 9 % of PS pupils reported anal sex as their first sexual act . Almost half of PS girls have had sex with adults , including teachers and relatives . ' Forced sex ' was reported by nearly half of PS and SS girls . Fourteen per cent of PS girls had already been pregnant , and over half of these pregnancies ended in illegally induced abortions . Despite a rather high ( 30 % ) lifetime rate of condom use , 33 % and 25 % of PS boys and girls , respectively , reported past experience of sexually transmitted diseases ( STDs ) . STD rates were lower among SS pupils who had a better knowledge of STDs/HIV and fertility issues and reported higher condom use . The survey demonstrated the great vulnerability of school-going adolescents of Mwanza Region to consequences of sexual intercourse . The response should urgently come in the from of comprehensive adolescent SRH programmes BACKGROUND Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate ( DMPA ) than in those who do not use hormonal contraception . We aim ed to assess whether two injectable progestin-only contraceptives , DMPA and norethisterone enanthate ( NET-EN ) , confer different risks of HIV-1 acquisition . METHODS We included data from South African women who used injectable contraception while participating in theVOICE study , a multisite , r and omised , placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9 , 2009 , and Aug 13 , 2012 . Women were assessed monthly for contraceptive use and incident infection . We estimated the difference in incident HIV-1infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospect i ve cohort . The VOICE trial is registered with Clinical Trials.gov , NCT00705679 . FINDINGS 3141 South African women using injectable contraception were included in the present analysis : 1788 (56·9%)solely used DMPA , 1097 ( 34·9 % ) solely used NET-EN , and 256 ( 8·2 % ) used both injectable types at different times during follow-up . During 2733·7 person-years of follow-up , 207 incident HIV-1 infections occurred ( incidence7·57 per 100 person-years , 95 % CI 6·61–8·68 ) . Risk of HIV-1 acquisition was higher among DMPA users ( incidence 8·62 per 100 person-years , 95 % CI 7·35–10·11 ) than among NET-EN users ( 5·67 per 100 person-years , 4·35–7·38;hazard ratio 1·53 , 95 % CI 1·12–2·08 ; p=0·007 ) . This association persisted when adjusted for potential confoundingvariables ( adjusted hazard ratio [ aHR ] 1·41 , 95 % CI 1·06–1·89 ; p=0·02 ) . Among women seropositive for herpes simplex virus type 2 ( HSV-2 ) at enrolment , the aHR was 2·02 ( 95 % CI 1·26–3·24 ) compared with 1·09 (0·78–1·52)for HSV-2-seronegative women ( pinteraction=0·07 ) . INTERPRETATION Although moderate associations in observational analyses should be interpreted with caution , thesefi ndings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence setting s where NET-EN is available . FUNDING National Institutes of Health , Mary Meyer Scholars Fund , and the Ruth Freeman Memorial Fund Objectives To estimate the effectiveness of c and i date microbicides BufferGel and 0.5 % PRO 2000 Gel ( P ) ( PRO 2000 ) for prevention of non-ulcerative sexually transmitted infections ( STIs ) . Methods Between 2005 and 2007 , 3099 women were enrolled in HIV Prevention Trials Network ( HPTN ) protocol 035 , a phase II/IIb evaluation of the safety and effectiveness of BufferGel and PRO 2000 for prevention of STIs , including Neisseria gonorrhoeae ( NG ) , Chlamydia trachomatis ( CT ) and Trichomonas vaginalis ( TV ) . Incidences of STIs were determined by study arm , and HRs of BufferGel and PRO 2000 versus placebo gel or no gel control groups were computed using discrete time And ersen-Gill proportional hazards model . Results The overall incidence rates were 1.6/100 person-years at risk ( PYAR ) for NG , 3.9/100 PYAR for CT and 15.3/100 PYAR for TV . For BufferGel versus placebo gel , HRs were 0.99 ( 95 % CI 0.49 to 2.00 ) , 1.00 ( 95 % CI 0.64 to 1.57 ) and 0.95 ( 95 % CI 0.71 to 1.25 ) for prevention of NG , CT and TV , respectively . For PRO 2000 , HRs were 1.66 ( 95 % CI 0.90 to 3.06 ) , 1.16 ( 95 % CI 0.76 to 1.79 ) and 1.18 ( 95 % CI 0.90 to 1.53 ) for prevention of NG , CT and TV , respectively . Conclusions The incidence of STIs was high during HIV Prevention Trials Network 035 despite provision of free condoms and comprehensive risk-reduction counselling , highlighting the need for effective STI prevention programmes in this population . Unfortunately , c and i date microbicides BufferGel and PRO2000 had no protective effect against gonorrhoea , chlamydia or trichomoniasis . Trial registration number NCT00074425 CONTEXT The current public debate regarding whether oral sex constitutes having " had sex " or sexual relations has reflected a lack of empirical data on how Americans as a population define these terms . OBJECTIVE To determine which interactions individuals would consider as having " had sex . " METHODS A question was included in a survey conducted in 1991 that explored sexual behaviors and attitudes among a r and om stratified sample of 599 students representative of the undergraduate population of a state university in the Midwest . PARTICIPANTS The participants originated from 29 states , including all 4 US Census Bureau geographic regions . Approximately 79 % classified themselves as politically moderate to conservative . MAIN OUTCOME MEASURE Percentage of respondents who believed the interaction described constituted having " had sex . " RESULTS Individual attitudes varied regarding behaviors defined as having " had sex " : 59 % ( 95 % confidence interval , 54%-63 % ) of respondents indicated that oral-genital contact did not constitute having " had sex " with a partner . Nineteen percent responded similarly regarding penile-anal intercourse . CONCLUSIONS The findings support the view that Americans hold widely divergent opinions about what behaviors do and do not constitute having " had sex . Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections ( STIs ) and HIV-1 in a cohort of Nairobi female sex workers ( FSWs ) . A question naire was administered and a medical examination was performed . HIV-negative women were r and omly assigned to either one gram azithromycin or placebo monthly . Mean age of the 318 women was 32 years , mean duration of sex work 7 years and mean number of clients was 4 per day . High-risk behaviour was frequent : 14 % practised anal intercourse , 23 % sex during menses , and 3 % used intravenous drugs . While 20 % reported condom use with all clients , 37 % never use condoms . However , STI prevalence was relatively low : HIV-1 27 % , bacterial vaginosis 46 % , Trichomonas vaginalis 13 % , Neisseria gonorrhoeae 8 % , Chlamydia trachomatis 7 % , syphilis 6 % and cervical intraepithelial neoplasia ( CIN ) 3 % . It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes , including a proposed trial of HIV prevention through STI chemoprophylaxis Objective : To examine the practice s of anal intercourse and dry sex within a cohort of female sex workers ( FSWs ) in Kenya , focusing on the prevalence and perceived risk of the practice s , demographic and behavioural correlates , and association with sexually transmitted infections ( STI ) . Methods : A survey was conducted among FSWs in Meru , Kenya , with 147 participants r and omly sample d from an existing cohort of self identified FSWs . Results : 40.8 % of participants reported ever practising anal intercourse and 36.1 % reported ever practising dry sex . Although the majority of women surveyed believed anal intercourse and dry sex to be high risk practice s for HIV infection compared with vaginal sex , about one third of women reported never or rarely using condoms during anal intercourse , and about 20 % never or rarely using condoms during dry sex . Reported consistent condom use was lower with both of these practice s than with penile-vaginal intercourse . Anal intercourse was associated with experience of recent forced sexual intercourse , while dry sex was not . Anal intercourse was almost always initiated by clients , whereas dry sex was likely to be initiated by the women themselves . Sex workers reported charging higher fees for both practice s than for vaginal intercourse . Both practice s were associated with reported symptoms and diagnoses of STI . Conclusions : Both anal intercourse and dry sex were common in this sample , and although perceived as high risk practice s , were not adequately protected with condom use . Education and other interventions regarding these high risk sexual behaviours need to be translated into safer practice s , particularly consistent condom use , even in the face of financial vulnerability We developed and evaluated a military-focused HIV prevention intervention to enhance HIV risk-reduction knowledge , motivation , and behaviors among Angolan soldiers . Twelve bases were r and omly assigned to HIV prevention or control conditions , yielding 568 participants . HIV prevention participants received training in preventing HIV ( 4.5 days ) and malaria ( 0.5 days ) . Control participants received the reverse . Monthly booster sessions were available after each intervention . We assessed participants at baseline , 3 and 6 months after the training . HIV prevention participants reported greater condom use and less unprotected anal sex at 3 months , as well as greater HIV-related knowledge and perceived vulnerability at 3 and 6 months . Within-group analyses showed HIV prevention participants increased condom use , reduced unprotected vaginal sex , and reduced numbers of partners at both follow-ups , while control participants improved on some outcomes at 3 months only . A military-focused HIV prevention intervention may increase HIV-related knowledge , motivation , and risk reduction among African soldiers UNLABELLED Young people are particularly vulnerable to unplanned sexual activities . This study sought to identify the sexual behaviors and risk of HIV among public secondary schools students in Nigeria . METHODS A cross-sectional survey of 521 students in eight r and omly selected public secondary schools . Respondents were selected by a multistage sampling technique from amongst the study population . Using a self-administered , semi-structured , pre-tested question naire , data were obtained concerning their sexual behaviors and influencing factors . RESULTS Most respondents ( n = 387 , 74.3 % ) were in late adolescence . Many knew the consequences of premarital sex as unplanned pregnancy , STI/HIV/AIDS , incomplete schooling , and guilt feelings . About 40 % of the respondents had been involved in sexual activities with partners who were classmates , neighbors , ' sugar daddies ' , teachers , or strangers ( party-mates or prostitutes ) . Heterosexual , oral , and anal forms of sex were practice d respectively by 78.1 % , 13.3 % , and 12.4 % of those who were sexually active . Sexual debut was 15.2 + /- 1.62 years . About 36 % of those sexually active had more than one partner , and about 14.8 % were aware that their partners had other partners . Only 8.6 % used a condom on a consistent basis , whereas 41.9 % had never used a condom at all . More than half the sexual activities were not pre-planned . The reasons given for engaging in such practice s were peer influence , financial reward , drug influence , fun , or experimentation . CONCLUSIONS Despite their ' above average ' level of knowledge of the consequences , the students were still involved in risky sexual behaviors . Behavioral change communications should be intensified among these adolescents Objective : To evaluate the feasibility , fidelity , and effectiveness of a human immunodeficiency virus ( HIV ) prevention intervention delivered to HIV-infected patients by counselors during routine clinical care in KwaZulu-Natal , South Africa . Methods : A total of 152 HIV-infected patients , aged 18 years and older , receiving clinical care at an urban hospital in South Africa , were r and omly assigned to intervention or st and ard-of-care control counselors . Intervention counselors implemented a brief risk reduction intervention at each clinical encounter to help patients reduce their unprotected sexual behavior . Self-report question naires were administered at baseline and 6 months to assess number of unprotected sex events in previous 3 months . Results : Intervention was delivered in 99 % of routine patient visits and included a modal 8 of 8 intervention steps . Although HIV-infected patients in both conditions reported more vaginal and anal sex events at 6-month follow-up than at baseline , patients who received the counselor-delivered intervention reported a significant decrease over time in number of unprotected sexual events . There was a marginally significant increase in these events among patients in the st and ard-of-care control condition . Conclusions : A counselor-delivered HIV prevention intervention targeting HIV-infected patients seems to be feasible to implement with fidelity in the South African clinical care setting and effective at reducing unprotected sexual behavior This study investigated involvement in substance use and sexual activities among adolescents in Cape Town , and specifically the associations between methamphetamine use and sexual risk behaviours . Data were collected from 15 r and omly selected and 15 matched schools in Cape Town via quantitative question naires . Students used h and -held computers ( PDAs ) to answer the questions . A total of 4605 grade 9 students were sample d. Male and female students were almost equally likely to have used methamphetamine at least once ( 13 % versus 12 % ) . Students who had used methamphetamine in the past 30 days were significantly more likely to have had vaginal , anal or oral sex than students who had never used it , to have been pregnant/been responsible for a pregnancy and to have been diagnosed with a sexually transmitted infection . Logistic regression analysis indicated significant associations between methamphetamine use in the past 12 months and engaging in vaginal and anal sex . Drug abuse and sexually transmitted infections ( STI ) prevention services should incorporate the link between drugs and STI into their prevention and education strategies , especially those aim ed at school-going adolescents A cross-sectional question naire survey was conducted among 2820 pupils in 22 r and omly selected primary schools in Kinondoni district , Tanzania . The objective was to identify the proportion of pupils who reported ever having had sexual intercourse , as well as sociodemographic and psychosocial factors and other sexual-related behaviours associated with heterosexual intercourse among pupils . About 13 % ( 376 ) of participating pupils reported having had heterosexual intercourse . The proportion of pupils who reported doing so varied significantly by age , sex , school grade and parents ' education . Regarding psychosocial factors , pupils who agreed that having sexual intercourse implies love for a partner and that sexual intercourse creates peer approval were significantly more likely to report having had heterosexual intercourse . Pupils who reported having a girl/boy friend , kissed a boy/girl , engaged in light petting , engaged in heavy petting or practised oral sex and anal sex were more likely to report ever having heterosexual intercourse . The implication s for programme and intervention development are discussed Objectives : To compare coital diaries and face-to-face interviews ( FFIs ) in measuring sexual behaviour among women at high risk of HIV . To assess the effect of differing levels of support from research ers on reporting in coital diaries and FFIs . Methods : Three groups of 50 women were r and omly selected from a cohort of food and recreational facility workers participating in a microbicide trial feasibility study and received differing levels of research er support . Minimum support involved delivering and collecting coital diaries weekly ; medium support included a weekly FFI and discussion of concerns ; intensive support also included an unscheduled mid-week visit when diaries were checked and concerns addressed . All respondents participated in an exit FFI , including questions on sexual behaviour over the four-week study period and study acceptability . Results : Sexual behaviours were generally reported more frequently in coital diaries than weekly or exit interviews . Vaginal and anal sex , male and female condom use , vaginal cleaning and lubrication , sex during menstruation and sex with irregular and regular partners were reported more frequently in coital diaries than exit interviews . In coital diaries , level of support was associated with reporting of vaginal sex and cleaning . In exit interviews , support level was associated with reporting of vaginal sex , vaginal cleaning and sex with regular , irregular and commercial partners . Women with minimum support reported least satisfaction with the research process . Women with intensive support were most likely to report that they informed someone about their study participation and that they completed diaries daily . Conclusion : Compared with FFIs , coital diaries result ed in higher reporting of socially stigmatised activities , and sexual behaviour reporting varied less by level of support . More research er support enhanced study acceptability OBJECTIVES We tested the efficacy of a sexual risk-reduction intervention for men in South Africa , where heterosexual exposure is the main mode of HIV transmission . METHODS Matched-pairs of neighborhoods in Eastern Cape Province , South Africa , were r and omly selected and within pairs r and omized to 1 of 2 interventions based on social cognitive theory and qualitative research : HIV/sexually transmitted infection ( STI ) risk-reduction , targeting condom use , or attention-matched control , targeting health issues unrelated to sexual risks . Sexually active men aged 18 to 45 years were eligible . The primary outcome was consistent condom use in the past 3 months . RESULTS Of 1181 participants , 1106 ( 93.6 % ) completed the 12-month follow-up . HIV and STI risk-reduction participants had higher odds of reporting consistent condom use ( odds ratio [ OR ] = 1.32 ; 95 % confidence interval [ CI ] = 1.03 , 1.71 ) and condom use at last vaginal intercourse ( OR = 1.40 ; 95 % CI = 1.08 , 1.82 ) than did attention-control participants , adjusting for baseline prevalence . No differences were observed on unprotected intercourse or multiple partnerships . Findings did not differ for sex with steady as opposed to casual partners . CONCLUSIONS Behavioral interventions specifically targeting men can contribute to efforts to reduce sexual risk behaviors in South Africa |
10,394 | 22,071,804 | Misoprostol administered orally is less effective ( more failures ) than the vaginal route ( RR 3.00 , 95 % CI 1.44 to 6.24 ) and may be associated with more frequent side effects such as nausea and diarrhoea .
5 ) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostagl and in .
Safe and effective medical abortion methods are available .
Combined regimens are more effective than single agents .
In the combined regimen , the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness .
Vaginal misoprostol is more effective than oral administration , and has less side effects than sublingual or buccal . | BACKGROUND Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s .
Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostagl and ins in the early 1970s and anti-progesterones in the 1980s .
The most widely research ed drugs are prostagl and ins ( PGs ) alone , mifepristone alone , methotrexate alone , mifepristone with prostagl and ins and methotrexate with prostagl and ins .
OBJECTIVES To compare different medical methods for first trimester abortion . | Objectives To compare the efficacy of two different regimens of mifepristone followed by misoprostol for medical abortion in women with menstrual delay of ≤ 35 days OBJECTIVE To examine the clinical efficacy of mifepristone 100 mg followed 2 days later by misoprostol 400 μg orally or 800 μg vaginally in women at up to 49 days ' gestation . METHODS Eighty participants received mifepristone 100 mg and then were r and omized to misoprostol , administered 48 hours later , at a dose of 400 μg orally ( group 1 ) or 800 μg vaginally ( group 2 ) . Women returned for follow‐up evaluations 24 ± 1 hour after using the misoprostol and then 2–3 weeks later . If abortion still had not occurred and the pregnancy was nonviable , the subject returned again after an additional 3 weeks . RESULTS Twenty‐four hours after receiving misoprostol , 34 ( 85 % ; 95 % confidence interval [ CI ] 71 % , 94 % ) of the 40 women in group 1 and 38 ( 95 % ; 95 % CI 85 % , 99 % ) of the 40 women in group 2 had complete abortions . Overall , complete abortion without surgical intervention occurred in 34 women in group 1 ( 85 % ; 95 % CI 71 % , 94 % ) and 40 women in group 2 ( 100 % ; 95 % CI 91 % , 100 % ; P = .03 ) . Four women in group 1 required suction aspiration for continuing pregnancy at the second follow‐up , compared with none in group 2 ( P = .12 ) . Side effects occurred with similar frequency in both treatment groups . CONCLUSION Low‐dose mifepristone ( 100 mg ) combined with vaginal misoprostol 800 μg may be an effective alternative to regimens using 200 or 600 mg of mifepristone with misoprostol Two doses , 200 and 400 micrograms , of misoprostol , administered vaginally every 12 hours , up to four times , were tested in 101 and 133 healthy women , respectively , for interruption of pregnancies with 35 through 77 days of amenorrhea . The proportion of women who aborted increased with longer duration of treatment and was significantly higher with 400 than with 200 micrograms ( 66 versus 46 percent at 48 hours ) . Significance was maintained after controlling by age , body weight , parity , previous abortion and gestational age . Abortions were classified as incomplete or complete , according to the presence or not of embryonic tissue in the uterine cavity , diagnosed by vaginal sonography . Vacuum aspiration was carried out in all cases not classified as complete abortion 48 hours after the initiation of treatment , or earlier in case of persistent bleeding or woman 's request . The possibility of increasing effectiveness by using higher dose , shorter intervals or longer duration of treatment is discussed Objectives To compare the efficacy of oral and vaginal administration of misoprostol after a single oral dose of 200 mg of mifepristone and to investigate whether the efficacy can be improved and the duration of bleeding shortened by continuing oral misoprostol for one week The purpose of this study was to compare tamoxifen to methotrexate , with respect to effectiveness , when followed by misoprostol to induce abortion . In the first phase , 198 women presenting for medical abortion at < 7 weeks gestation were r and omized to receive either 40 mg of tamoxifen , followed 2 to 3 days later by 800 micrograms of misoprostol self-administered vaginally or 50 mg/m2 of methotrexate , followed 5 to 7 days later by the same dose of misoprostol . In the second phase , 200 women were r and omized to receive 20 mg tamoxifen twice daily for 4 days , followed by 800 micrograms misoprostol or the same regimen of methotrexate and misoprostol as in phase 1 . The main outcome measure was success rate determined by the number of women who aborted without surgery . In phase 1 , the success rate was higher in the methotrexate group ( 93.0 % ) compared to the tamoxifen group ( 85.7 % ) ( p = 0.045 ) . In the tamoxifen group , nine of 98 women had incomplete abortions with symptoms requiring a surgical aspiration , compared to one of 100 women in the methotrexate group . In phase 2 , the success rates were 90.9 % in the methotrexate group compared to 84.7 % in the tamoxifen group ( p = 0.20 ) . The side effects were less in the tamoxifen group in phase 1 but not in phase 2 . When tamoxifen is given as a single dose , it is less effective than methotrexate but when it is given 20 mg twice daily for 4 days , there is no significant difference . Tamoxifen does not appear to have any benefits over methotrexate OBJECTIVE To compare the efficacy and side-effects of mifepristone 75 mg in capsule form versus 150 mg in tablet form followed by misoprostol for medical termination of early pregnancy . STUDY DESIGN In a prospect i ve r and omized , double-blind , placebo-controlled trial , a total of 480 women who were 49 days or less pregnant were r and omized by means of a r and om number table to receive either two tablets in the morning and one tablet 12 h later for 2 days ( group A ) or three capsules orally twice daily for 2 days , the first dose being double all subsequent doses ( group B ) . After a further 48 h , 600 microg misoprostol was given orally . Successful abortion was defined as complete abortion with no need for surgical aspiration . RESULTS There were no significant differences between the two study groups in the rates of complete abortion ( 95.4 % in group A versus 96.3 % in group B ) , incomplete abortion ( 3.8 % in group A , 3.3 % in group B ) and continued pregnancy ( 0.8 % in group A , 0.4 % in group B ) . No significant difference in the duration and amount of vaginal bleeding was observed . The incidence of side-effects , such as vomiting , nausea , headache , diarrhea and lower abdominal pain was similar in the two groups . CONCLUSIONS Our results indicate that 75 mg mifepristone in capsule form combined with 600 microg misoprostol is as effective and safe as 150 mg mifepristone in tablet form for the termination of pregnancy up to 49 days OBJECTIVE Our purpose was to determine whether vaginal misoprostol 7 days rather than 3 days after methotrexate injection increases the percent of successful abortions on the day of misoprostol administration . STUDY DESIGN A r and omized controlled trial was performed in women requesting an abortion at < or = 56 days ' gestation . Eighty-six women were treated with methotrexate 50 mg/m2 intramuscularly followed 3 days ( group 1 ) or 7 days ( group 2 ) later by vaginal misoprostol 800 micrograms . The misoprostol dose was repeated if the abortion did not occur . RESULTS Complete abortion occurred in 38 of 46 ( 83 % ) patients in group 1 and 39 of 40 ( 98 % ) in group 2 ( p = 0.033 ) . Of the women with complete abortions , 30 of 46 ( 65 % ) in group 1 and 27 of 40 ( 68 % ) in group 2 aborted the same day as the first or second dose of misoprostol ( p = 0.823 ) . Vaginal bleeding lasted 14 + /- 5 ( mean + /- SD ) days in group 1 and 17 + /- 9 days in group 2 . The remaining women aborted after a delay of 24 + /- 6 days in group 1 and 28 + /- 13 days in group 2 . For these women vaginal bleeding lasted 18 + /- 17 and 14 + /- 7 days , respectively , and the human chorionic gonadotropin-beta level was < or = 25 IU/L by 22 + /- 7 days after the abortion in group 1 and 19 + /- 9 days in group 2 . Treatment failures in group 1 were four continuing pregnancies ( 9 % ) , two incomplete abortions ( 4 % ) , and two women who requested surgical termination after receiving both medications ( 4 % ) . The treatment failure in group 2 was an incomplete abortion . Methotrexate and misoprostol side effects were infrequent . CONCLUSIONS Methotrexate and vaginal misoprostol are more effective abortifacients when the misoprostol is given 7 days rather than 3 days after methotrexate . This treatment regimen may offer an alternative to surgical abortion or the use of antiprogestins and prostagl and in for medical abortion OBJECTIVE We investigated safety , efficacy , and acceptability of an oral regimen of medical abortion compared with surgical abortion in three developing countries . STUDY DESIGN Women ( n = 1373 ) with amenorrhea < or = 56 days chose either surgical abortion ( as provided routinely ) or 600 mg of mifepristone followed after 48 hours by 400 micrograms of misoprostol . This is the appropriate design for study ing safety , efficacy , and acceptability among women selecting medical abortion over available surgical services . RESULTS The medical regimen had more side effects , particularly bleeding , than did surgical abortion but very few serious side effects . Failure rates for medical abortion , although low , exceeded those for surgical abortion : 8.6 % versus 0.4 % ( China ) , 16.0 % versus 4.0 % ( Cuba ) , and 5.2 % versus 0 % ( India ) . Nearly half of failures among medical clients were not true drug failures , however , but surgical interventions not medically necessary ( acceptability failures or misdiagnoses ) . Women were satisfied with either method , but more preferred medical abortion . CONCLUSION Medical abortion can be safe , efficacious , and acceptable in developing countries Objective To examine the clinical efficacy of mifepristone 600 mg followed on the same day or two days later by misoprostol 400μg orally in women undergoing medical termination of pregnancy whose pregnancies have a gestational age up to 49 days OBJECTIVE : To study the efficacy , safety , and acceptability of oral immediately swallowed and buccal misoprostol 800 mcg after mifepristone 200 mg for terminating pregnancy through 63 days since the last menstrual period ( LMP ) . METHODS : This seven-site study r and omly assigned 966 women seeking abortions to oral or buccal misoprostol 800 mcg 24–36 hours after mifepristone 200 mg with 7–14-day follow-up . RESULTS : Success rates in the oral and buccal groups were 91.3 % ( 389 of 426 ) and 96.2 % ( 405 of 421 ) , respectively ( P=.003 ; relative risk [ RR ] 0.95 , 95 % confidence interval [ CI ] 0.92–0.98 ) . Ongoing pregnancy occurred in 3.5 % ( 15 of 426 ) of women who took oral misoprostol compared with 1.0 % ( 4 of 421 ) of women in the buccal group ( P=.012 ; RR 3.71 , 95 % CI 1.24–11.07 ) . Through 49 days since the LMP , oral and buccal regimens performed similarly , but success with oral misoprostol decreased as pregnancy advanced . In pregnancies of 57–63 days since the LMP , success with oral misoprostol fell below 90 % , whereas that with buccal remained high ( oral 85.1 % [ 97 of 114 ] , buccal 94.8 % [ 109 of 115 ] , P=.015 , RR 0.90 , 95 % CI 0.82–0.98 ) . Furthermore , in this gestational age group , there were significantly more ongoing pregnancies among women who took misoprostol orally ( 7.9 % [ 9 of 114 ] ) compared with buccally ( 1.7 % [ 2 of 115 ] ; P=.029 , RR 4.54 , 95 % CI 1.0–20.55 ) . Adverse effect profiles were similar , although fever and chills were reported approximately 10 % more often among women who took buccal misoprostol . Satisfaction and acceptability were high for both methods . CONCLUSION : Buccal misoprostol 800 mcg after mifepristone 200 mg is a good option for medical abortion through 63 days since the LMP . Oral misoprostol 800 mcg is also a safe and effective alternative , although success rates diminish with increasing gestational age . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00386867 LEVEL OF EVIDENCE : BACKGROUND Vaginal misoprostol has been shown to be an effective single agent for medical abortion . This r and omized , double-blinded , placebo-controlled trial compared a regimen of mifepristone and misoprostol with misoprostol alone for termination of early pregnancy . METHODS 250 women with gestations < or = 56 days were r and omized by a r and om number table to receive either 200 mg mifepristone orally or placebo followed 48 h later by 800 microg vaginal misoprostol . Administration of misoprostol was repeated every 24 h up to three doses if abortion failed to occur . Abortion success was defined as complete abortion without the use of surgical aspiration . RESULTS Successful medical abortions occurred in 114 out of 119 subjects ( 95.7 % ) after mifepristone followed by vaginal misoprostol . In all , 110 out of 125 subjects ( 88.0 % ) successfully aborted after placebo and vaginal misoprostol . The higher success rate of complete abortion with the mifepristone and misoprostol regimen was statistically significant compared with the placebo and misoprostol regimen ( P < 0.05 ) . CONCLUSIONS A regimen of mifepristone and misoprostol was significantly more effective for termination of pregnancies < or = 56 days than misoprostol alone . The 88 % efficacy obtained with vaginal misoprostol alone may be clinical ly acceptable when mifepristone is not available Although it has been demonstrated that a combination of mifepristone and a prostagl and in is an effective method of inducing abortion in early pregnancy , the optimum dose of the antigestogen is unknown . Women ( n = 220 ) requesting abortion in early pregnancy ( < or = 63 days amenorrhoea ) were r and omized to receive a single dose of either 600 or 200 mg mifepristone followed 48 h later by a single dose of 600 micrograms misoprostol by mouth . The percentage of women who had a complete abortion ( 93.6 % confidence interval 90.4 - 95.5 % ) was identical in the two groups . There was no significant difference in the number of women who passed the fetus within 4 h of receiving the prostagl and in ( 64 versus 74 % ) , the days of bleeding ( 14.6 + /- 1.1 versus 15.3 + /- 0.9 ) nor in the onset of the next period ( 39.7 + /- 1.3 versus 36.7 + /- 1.3 ) respectively between the groups receiving 200 or 600 mg mifepristone . However , the complete abortion rate was significantly higher in women < or = 49 days compared to women 50 - 63 days amenorrhoea ( 97.5 versus 89.1 % respectively ; P < 0.02 ) . There was no difference in any of the other parameters at different weeks of gestation . We conclude : ( i ) that the recommended dose of mifepristone could be reduced from 600 to 200 mg without loss of clinical efficacy , ( ii ) that the combination of mifepristone and 600 micrograms misoprostol is a highly effective alternative to vacuum aspiration for inducing abortion in women < 50 days amenorrhoea and ( iii ) at gestation > 56 days , this combination may result in too many incomplete abortions to be clinical ly acceptable The purpose of this study was to compare the outcome and side effects of using the drugs methotrexate and misoprostol , alone or in combination , to induce abortion . A total of 108 subjects who had requested elective termination of pregnancy and medical abortion at 9 weeks gestation or less were r and omized into three groups . The first group received 50 mg/m2 intramuscular ( i.m . ) methotrexate on day 1 and , if the hCG level had risen by > 50 % of the initial level on day 4 , a second dose was given . They were then followed-up at weekly intervals up to day 21 . Group 2 received 800 micrograms vaginal misoprostol on day 1 and , if ultrasound showed a gestational sac on day 4 , they received a repeat dose and were re-examined on day 7 . Group 3 received 50 mg/m2 methotrexate intramuscularly followed 3 days later by 800 micrograms vaginal misoprostol and were re-examined on day 7 . Complete abortion occurred in 25 ( 69 % ) of the 36 subjects in group 1 , 21 ( 58 % ) of the 36 subjects in group 2 , and 32 ( 89 % ) of the 36 subjects in group 3 . The complete abortion rate in group 3 was significantly higher than that of both group 1 and group 2 ( p < 0.05 ) . The incomplete abortion rate was significantly higher in group 2 as compared with both of the other groups ( p < 0.05 ) . There were significant differences between the mean gestational age of the successful abortions and the failures in group 1 ( no abortion occurred at more than 49 days gestation ) , but not in groups 2 or 3 . Vaginal bleeding in subjects who successfully aborted began within 16 + /- 4 days in group 1 after the first dose , and within 24 h in 18 ( 86 % ) of the 21 subjects in group 2 and 27 ( 84 % ) of the 32 subjects in group 3 after the misoprostol dose . The drugs caused no serious or prolonged side effects . The combination of methotrexate and misoprostol is a more effective abortifacient regimen than when either drug is used alone Although a combination of mifepristone and a prostagl and in is a safe , acceptable alternative to vacuum aspiration for inducing abortion in early pregnancy , the longer period of vaginal bleeding after medical abortion is a disadvantage . The present study investigated whether administration of the combined oral contraceptive pill ( COC ) or the injection of methotrexate at the time of abortion would shorten the period of vaginal bleeding after medical abortion . After having a medical abortion induced with mifepristone ( 200 mg ) and 0.5 mg gemeprost pessary , 80 women were r and omized to four groups of 20 women each ; Group A , COC ; Group B , control ; Group C , 50 mg/m2 methotrexate ; and Group D , placebo injection . There was no significant difference in the duration of bleeding between Groups A and B ( median 14 and 17 days ) or between Groups C and D ( 18 and 15 days ) , or in the amount of bleeding ( 4 days of heavy bleeding in each group ) . The first period occurred sooner in Group A who took the COC ( median/range : 25/15 - 54 control group versus 32/16 - 46 days , p < 0.04 ) . The administration of methotrexate was associated with a temporary elevation in liver enzyme concentration in one woman . It is concluded that women who wish to use COC can start immediately after medical abortion . Addition of methotrexate after abortion has no significant beneficial effect on patterns of bleeding and can not be recommended CONTEXT The conventional timing of misoprostol administration after mifepristone for medical abortion is 2 days , but more flexible intervals , which may make the regimen more convenient , have not been studied . OBJECTIVE To determine whether vaginal misoprostol administered 1 , 2 , or 3 days after mifepristone influences safety or effectiveness for abortion at up to 56 days ' gestation . DESIGN Prospect i ve , r and omized , open-label trial conducted from March 1998 to June 1999 . SETTING Sixteen US primary care and referral abortion facilities . PATIENTS A total of 2295 healthy patients aged 18 years or older who were 56 or fewer days pregnant . Forty ( 1.7 % ) were lost to follow-up . INTERVENTIONS Patients received 200 mg of oral mifepristone and were r and omly assigned to self-administer 800 microg of vaginal misoprostol at home 1 ( n = 745 ) , 2 ( n = 778 ) , or 3 ( n = 772 ) days later . Women returned to the clinic up to 8 days after mifepristone for ultrasonographic evaluation . A second dose of misoprostol was administered if the abortion was not complete . Patients with continuing pregnancy , excessive bleeding , or retained pregnancy tissue 5 weeks later received an aspiration curettage . MAIN OUTCOME MEASURES Effectiveness of the procedure ( ie , a complete medical abortion without surgical intervention ) , adverse effects , acceptability of the procedure based on patient question naires , reasons for surgical intervention , and adverse outcomes , compared among the study groups . RESULTS Of the 2255 women completing follow-up , complete medical abortion rates were 98 % ( 95 % confidence interval [ CI ] , 97%-99 % ) among those using misoprostol after 1 day , 98 % ( 95 % CI , 97%-99 % ) for those using misoprostol after 2 days , and 96 % ( 95 % CI , 95%-97 % ) among those using misoprostol after 3 days . Fifty-five subjects aborted before taking misoprostol , 9 had early surgery , and 103 did not take misoprostol on their assigned day . No blood transfusions were required . Cramping and nausea were the most common adverse effects reported , with similar percentages of patients in all 3 groups reporting such effects . Thirteen unexpected or serious adverse events occurred : 6 in those using misoprostol after 1 day ; 4 in those using it after 2 days ; and 3 in those using it after 3 days . Nearly all women ( > 90 % ) found the procedure to be acceptable . CONCLUSIONS Our results suggest that vaginal misoprostol , 800 microg , can be used from 1 to 3 days after mifepristone , 200 mg , for early medical abortion , and need not be administered strictly 48 hours after mifepristone . JAMA . 2000;284:1948 - 1953 Misoprostol and mifepristone have been shown to be effective for medical abortion up to 9 weeks of gestation . When used alone , the successful complete abortion rate dropped to approximately 60 % . It has been demonstrated that by adding water to misoprostol , the success rate rose to 92 % . This is the first r and omized study to investigate the efficacy of misoprostol and water versus misoprostol alone for first trimester medical abortion in women at < /= 9 weeks of gestation . Eighty women were r and omly assigned to group 1 ( water added to misoprostol ) and group 2 ( misoprostol alone ) . Vaginal misoprostol 800 microgram was given on days 1 , 3 and 5 . If the woman did not require vacuum aspiration during the period up to the return of first menstruation after medical abortion , the outcome was classified as complete abortion . The incidence of side-effects and the acceptability were assessed through a st and ardized question naire during and after the abortion . The complete abortion rate appeared higher when water was added but the difference did not reach statistical significance . Gastro-intestinal side-effects were common but well tolerated in both groups . Overall , 40 % of the women preferred a surgical method in the future because of the high failure rate . With an overall complete abortion rate of 85 % , it is probably not a clinical ly acceptable method even if the addition of water can improve the results . We conclude that the addition of water onto misoprostol tablets does not improve its efficacy in first trimester medical abortion . Misoprostol alone is not recommended for medical abortion ( up to 9 weeks of pregnancy ) because of the high failure rate and low acceptability OBJECTIVE To find out the optimal doses regimen of mifepristone with misoprostol for termination early pregnancy . METHODS A r and omized comparative study in 1,621 women requesting medical abortion at < or = 49 days from 9 hospitals was conducted in Hebei , women were r and omly divided into 2 groups by 2:1 ratio . Study group ( n = 1,118 ) women took mifepristone 50 mg immediately , then 25 mg b. i. d(total amount of 300 mg ) , plus misoprostol 600 micrograms at 8:00 in the morning on 3th day , and plus misoprostol 200 micrograms respectively at 8:00 in the morning on 4th , 5th , 6th day . In control group ( n = 494 ) , mifepristone 50 mg immediately , then , 25 mg b. i. d ( total amount of 150 mg ) , plus misoprostol 600 micrograms at 8:00 in the morning on 3th day . RESULTS In study group and control group , the complete abortion rate was 98.39 % and 88.06 % respectively , bleeding duration was ( 8.2 + /- 2.8 ) days and ( 12.3 + /- 3.9 ) days . There was no difference of side effects between the two groups . CONCLUSION Mifepristone taken 300 mg plus misoprostol 1,200 micrograms orally for 6 days is an optimal dose regimen for termination of early pregnancy A prospect i ve trial including 300 pregnant women seeking elective abortion was conducted to evaluate the safety and efficacy of methotrexate and misoprostol for abortion at < or = 63 days ' gestation . Subjects received methotrexate 50 mg orally and were r and omly allocated to receive 800 micrograms of misoprostol vaginally 3 , 4 , or 5 days after administration of the methotrexate . The misoprostol dose was repeated 48 and 96 h later if abortion did not occur . Outcome measures included successful abortion ( complete abortion without requiring a surgical procedure ) and side effects . Complete abortion occurred in 273 of 300 patients ( 91 % , 95 % , CI 87 , 94 % ) patients . No significant statistical differences were found in the success rates when misoprostol was given days 3 , 4 , or 5 after the administration of methotrexate ( p = 0.69 ) . Vaginal bleeding lasted 7.1 + /- 3.8 days , spotting 4.1 + /- 2.5 days , and total bleeding 11.2 + /- 4.1 days . Side effects for methotrexate were minimal , whereas , for misoprostol they were mild and transient except for pain . The use of methotrexate and misoprostol together could be an alternative to the intramuscular use of methotrexate or the use of antiprogestins and prostagl and in for medical abortion In France , pregnant women with amenorrhoea of no more than 49 days intending to terminate pregnancy can choose between a surgical abortion via vacuum aspiration under local or general anesthesia and a drug method combining Mifepristone orally administered ( RU 486 degrees ) , with a prostagl and in analogue . This prospect i ve survey was conducted to study the conditions under which women choose their abortion method , and to evaluate the acceptability of each method after the abortion . The data gathered from 488 women were analyzed according to their initial decision , and then according to the method actually used . The majority ( 62 % ) chose RU 486 . The women 's choice was found to be linked to sociodemographic characteristics such as age , education , occupation , geographic origin , and certain attitudes towards pregnancy , as well as to the individual criteria of each method . The women who chose the drug protocol had most often already made their decision before going to the family planning center ( 68 % ) , having been advised by their doctor ( 20 % ) . They were slightly less satisfied with the abortion experience than they had expected : 12.4 % were unsatisfied in the RU group and 3.6 % in the aspiration group . They needed more rest and quiet afterwards ( 50 % ) than the other women . They were distinguished by their desire to verify the expulsion ( 63 % ) . The length of pregnancy is therefore not the only criterion to be considered when recommending one or other of these methods : the women concerned have different requirements and should have several possibilities to choose from Milligram‐range doses of E2 prostagl and ins have long been used to induce labor or abortion in the second and third trimesters of pregnancy . Enprostil , a synthetic dehydroprostagl and in E2 structural analogue , is administered in microgram doses for the treatment of acute duodenal ulcer and acute gastric ulcer . This study examined the effect of the ulcer‐healing dose and twice the ulcer‐healing dose upon women in the first trimester of pregnancy . Two hundred and seven women who had requested legal abortion in the first trimester participated in two r and omized , double‐blind , placebo‐controlled , parallel studies . They received two doses of enprostil 35 μg ( the recommended dose for the treatment of duodenal and gastric ulcer ) ( n=51 ) , 70 μg ( twice the recommended dose ) ( n=53 ) , or placebo ( n = 103 ) 12 h apart . No drug‐induced abortions occurred in any of the first‐trimester pregnancies . Vaginal bleeding occurred in 4 % of volunteers receiving the lower dose and 4 % receiving the higher dose of enprostil . Vaginal bleeding occurred in up to 2 % of volunteers on placebo . Although not recommended for pregnant women , if enprostil is given inadvertently to pregnant women with ulcers , it is unlikely to endanger the pregnancy during the first trimester The antiprogestin RU 486 ( mifepristone ) is highly effective in inducing early abortion in women only if the compound is combined with a prostagl and in analogue . A new related antiprogestin , ZK 98,734 , has been reported in animal studies to be much more potent as an abortifacient than mifepristone , concomitant with less antiglucocorticoid activity . The aim of the present two-centre study was to explore the abortifacient efficacy and plasma concentrations of ZK 98,734 in women seeking abortion . A total of 96 pregnant women with amenorrhoea of < 49 days were treated with oral doses of 12.5 , 25 , 50 or 100 mg ZK 98,734 twice daily for 4 days . The overall rate of complete abortion and continuing live pregnancies was 68 and 20 % respectively , i.e. results comparable with treatment with mifepristone alone . No dose-response relationship was noted . In patients with complete abortion , signs of luteal dysfunction in terms of oestradiol and progesterone production were evident on the fourth treatment day , in contrast to patients with failures . Increased amounts of cortisol and prolactin were found during treatment both in successfully treated patients and failures , whereas aldosterone values remained unaffected . The effect on cortisol may indicate some antiglucocorticoid activity in the human . The concentrations of ZK 98,734 in peripheral blood after 25 , 50 and 100 mg twice daily for 4 days were similar . The values were slightly above 0.5 mumol/l on the second day of treatment . Maximal concentrations of 0.7 mumol/l were seen on treatment day 4 . Plasma concentrations of ZK 98,734 did not differ in cases of complete abortion and failures . ( ABSTRACT TRUNCATED AT 250 WORDS Previous studies of medical abortion with mifepristone and a prostagl and in have reported percentages of subjects who experience cramping and /or bleeding relative to prostagl and in use . This is the first analysis of cramping and bleeding onset patterns in subjects treated with low-dose ( 200 mg ) mifepristone and 800 microg vaginal misoprostol at 24 , 48 , or 72 h after mifepristone . We analyzed the cramping and bleeding onset patterns in subjects up to 8 weeks pregnant who used 800 microg vaginal misoprostol at 24 , 48 , or 72 h after 200 mg of oral mifepristone . We collected data from subjects ' symptom diaries and divided symptom onset into 3 categories : before misoprostol use , 0 - -12 h following misoprostol , and more than 12 h after misoprostol . Of the 2,302 subjects , cramping and bleeding onset data were available for 2,030 ( 88 % ) and 2,123 ( 92 % ) , respectively . Across all groups , 230 ( 11 % ) experienced cramping and 445 ( 21 % ) experienced bleeding before misoprostol use . There was a significantly higher percentage of subjects who experienced early cramping and /or early bleeding between the three treatment groups , and this was related to the interval between mifepristone and misoprostol . In the 12 h following misoprostol administration , cramping and bleeding patterns were similar in the three groups . The longer subjects waited to insert misoprostol , the more likely they were to experience early cramping and /or bleeding . After misoprostol insertion , cramping and bleeding patterns are similar regardless of treatment group . Patients and providers can not rely on symptom onset to predict treatment success A multicentre r and omized open clinical trial was conducted to compare the efficacy and side effects of two regimens of mifepristone with misoprostol , and mifepristone with PG05 for termination of early pregnancy ( amenorrhoea < = 49 days ) . Six-hundred women in early pregnancy , who requested medical abortion were r and omly allocated into 3 groups . In group 1 ( n = 301 ) , an initial dose of mifepristone 50 mg was given , followed by 25 mg every 12 hours up to a total dose of 150 mg mifepristone , plus a single oral dose of misoprostol 600 micrograms in the morning of the third day . In group 2 ( n = 150 ) , the same regimen of mifepristone was given , but dl-15-methyl PGF2 alpha ( PG05 ) 1 mg vaginal suppository was inserted on the third day . In group 3 ( n = 149 ) , a single dose of mifepristone 200 mg was given and misoprostol 600 micrograms was used as in group 1 . The complete abortion rate were 94.4 % , 97.3 % , and 94.6 % for group 1 , 2 and 3 , respectively . 3.0 , 2.0 and 2.7 % of women had incomplete abortion , and 1.7 , 0.7 and 2.0 % of women in the 3 groups were treatment failures ; in the remaining 1 % in group 1 and 0.7 % in group 3 , treatment outcome could not be determined . There were no significant differences among the 3 groups . Lower abdominal pain was the main complaint which was reported by 82 % of the subjects after PGs administration . The incidence of diarrhoea in PG05 group ( 38.7 % ) was significantly higher than that in the other two groups ( 21.6 and 20.1 % ) ( P < 0.001 ) , and so was vomiting . It was concluded that misoprostol , as an orally effective prostagl and in , in combination with mifepristone for induced abortion of early pregnancy was as effective as PG05 vaginal suppository . Besides , it has advantages of convenience of use , less side effects , easy storage and transfer , and low cost One-hundred- and -twenty women of less than 56 days amenorrhoea were treated with a single dose of 600 mg of mifepristone in combination with half or a whole 1 mg gemeprost vaginal pessary . Complete abortion was induced in 119 ( 99 % ) women and there were no continuing pregnancies . There were few gastro-intestinal side effects following prostagl and in . The smaller dose of prostagl and in caused significantly less severe pain . This study confirmed the effectiveness of mifepristone and prostagl and in for the induction of early abortion but suggests that more research should be carried out to determine the lowest effective doses of both drugs OBJECTIVES To compare the experience of pain , need of analgesic interventions , preference and acceptability in medical abortion up to 49 days of amenorrhea with mifepristone and orally versus vaginally administered misoprostol . STUDY DESIGN Ninety-seven women were r and omised to oral misoprostol , n=48 , or vaginal misoprostol , n=49 . On day 1 of the study , both the groups received 600 mg of mifepristone . On day 3 of the study , one group received 0.4 mg of misoprostol orally and the other group received 0.8 mg of misoprostol vaginally . RESULTS Even though oral administration of misoprostol seemed to be associated with a higher rate of gastrointestinal side effects , women in both the groups showed a clear preference towards the oral route of administration . The willingness to administer the misoprostol at home was also higher among the women in the oral group , which may in part depend on a more positive/less negative experience of the abortion . CONCLUSION A majority of women prefer oral administration of misoprostol in early medical abortion BACKGROUND A 400 mcg dose of sublingual misoprostol has high efficacy and few side effects when used with 200 mg mifepristone for medical abortion through 63 days ' gestation . STUDY DESIGN Eligible and consenting women ( n=480 ) were r and omized to 400 mcg of misoprostol sublingually or orally , 24 h after 200 mg of mifepristone . Abortion status was assessed two weeks later . RESULTS Complete abortion occurred in 98.7 % of the sublingual group and 94.0 % of the oral group ( p value=.006 , RR : 1.05 , 95 % CI=1.01 - -1.09 ) . Over 90 % of women in both arms expressed high satisfaction with the method . Side effects were similar in both groups , with only fever or chills reported by significantly more women in the sublingual arm . CONCLUSIONS The sublingual route appears superior to the regimen of 400 mcg misoprostol used orally and may be a good option for mifepristone medical abortion A prospect i ve trial was conducted including 300 pregnant women seeking elective abortion to evaluate the efficacy and acceptability of methotrexate and misoprostol for abortion at < or = 56 days gestation . Subjects received methotrexate 50 mg/m2 intramuscularly followed 7 days later by misoprostol 800 micrograms vaginally . The misoprostol dose was repeated the next day if the abortion did not occur . Efficacy is reported elsewhere . Subjects were question ed before the study as to their reasons for choosing a medical abortion and past experience with surgical abortion . After the study was completed , the women were question ed about their medical abortion experience . All questions were asked in an open-ended manner . Main outcome measures included reasons for abortion and study participation , attitudes about the nonsurgical abortion experience , and feelings about preference of nonsurgical or surgical abortion . The most common reason cited as to why women chose to have a nonsurgical abortion was to avoid some aspect of the surgery ( 48.4 % ) . The percent of women who cited that avoiding surgery was an important reason in their choice of nonsurgical abortion varied by study site and according to whether the woman had a prior surgical abortion . Upon completion of the study , 73.4 % of women stated it was a good experience , 19.5 % a neutral experience , 7.1 % a bad experience , and 1.0 % gave no response . When asked what method they would choose if they had to have another abortion , 83.5 % would choose this method of medical abortion rather than a surgical abortion . Intramuscular methotrexate and vaginal misoprostol are an acceptable and desirable method of abortion In France , mifepristone in association with orally administered misoprostol is widely used for the early termination of pregnancy ( up to 49 days ' gestation ) . In other centers , mifepristone in association with vaginally administered misoprostol has also been used . The aim of the present study was to compare the efficacy and tolerance of mifepristone in association with misoprostol administered orally or vaginally for the termination of pregnancy of up to 49 days ' gestation . A total of 237 women were enrolled in the study . All women received 600 mg mifepristone administered orally and 400 μg misoprostol administered either orally ( n = 119 ) or vaginally ( n = 118 ) . A second dose of 400 μg misoprostol was administered if women had not expelled the pregnancy within 3 h. Women were r and omized into treatment groups according to the day of their admission . The overall success rate was 98.7 % and there was no significant difference in efficacy between the two groups . There was one treatment failure in the group in which misoprostol was administered orally . Of those women who aborted within 3 h of administration of the first dose of misoprostol , the route of administration of misoprostol did not influence the time to abortion . Of the women who received a second dose of misoprostol , the time to abortion was shorter in those who received misoprostol orally ( 52 min versus 77 min ) . Tolerance was assessed by visual analog scales and was similar for both groups . In both groups , women preferred the oral route of administration A r and omized trial was conducted including 287 pregnant women seeking elective abortion to compare the efficacy of misoprostol given 3 , 4 , or 5 days after methotrexate for abortion at < or = 63 days ' gestation . Subjects received 50 mg/m2 methotrexate intramuscularly and were r and omly allocated to self-administer vaginally 800 micrograms of misoprostol 3 , 4 , or 5 days after the methotrexate . The misoprostol dose was repeated 48 and 96 h later if the abortion did not occur . Outcome measures included successful abortion ( complete abortion without requiring a surgical procedure ) , and side effects . Eighty-six cases ( 93 % ; 95 % confidence interval [ CI ] 85%-97 % ) aborted in Group I ; 90 cases ( 92 % ; 95 % CI 84%-96 % ) aborted in Group II ( relative risk [ RR ] = 1.09 ; RR 95 % CI 0.38 - 3.14 ) ; and 89 ( 93 % ; 95 % CI 86%-97 % ) cases aborted in Group III ( RR = 0.97 ; RR 95 % CI 0.33 - 2.87 ) . No significant statistical differences were obtained for the success rates when misoprostol was given days 3 , 4 , or 5 after the administration of methotrexate ( p = 0.97 ) nor with any of the characteristics of the subjects . Complete abortion occurred in 265/287 ( 92 % ; 95 % CI 89%-95 % ) patients . Twenty-two cases ( 8 % ; 95 % CI 5%-11 % ) result ed in failure . Side effects for methotrexate were minimal while for misoprostol they were moderate . This combination could be an alternative to surgical abortion or the use of antiprogestins and prostagl and ins for medical abortion BACKGROUND A combination of mifepristone and misoprostol provides an effective method of medical abortion for early pregnancy . This is the first r and omized trial comparing the use of sublingual misoprostol with vaginal misoprostol in combination with mifepristone for termination of early pregnancies up to 63 days . METHODS A total of 224 women who requested legal termination of pregnancy up to 63 days were r and omized by computer- generated list into two groups and given 200 mg of oral mifepristone followed 48 h later by either 800 micro g of sublingual ( n = 112 ) or vaginal ( n = 112 ) misoprostol . RESULTS Complete abortion occurred in 98.2 % ( 95 % CI : 93 - 99 ) of women in the sublingual group and 93.8 % ( 95 % CI : 88 - 97 ) in the vaginal group . There were three ongoing pregnancies in the vaginal group but none in the sublingual group . The median duration of vaginal bleeding was 17 days . There was no serious complication . Fever , chills and gastrointestinal side-effects ( nausea , vomiting and diarrhoea ) were significantly more common in the sublingual group . CONCLUSIONS The combination of mifepristone and misoprostol is effective for medical abortion up to 63 days . Both the sublingual and vaginal are effective routes of administration . Further r and omized trials are required to find out the optimal dose of sublingual misoprostol that can give the highest complete abortion rate and lowest incidence of side-effects Mifepristone ( 600 mg ) in combination with a prostagl and in has been demonstrated to be a safe , acceptable alternative to vacuum aspiration for induction of abortion in the first 9 weeks of pregnancy . However , the efficacy and side-effects of different prostagl and ins used in combination with mifepristone have not been assessed in a r and omized trial . In this study , 800 women seeking an abortion at gestational age < or = 63 days amenorrhoea were r and omized to receive either 0.5 mg gemeprost by vaginal pessary ( group I ) or 600 micrograms misoprostol ( group II ) by mouth approximately 48 h after taking 200 mg mifepristone by mouth . The side-effects and number of complete abortions were used as measures of efficacy . There was no significant difference in the rate of complete abortion between group I [ 96.7 % ; 95 % confidence interval ( CI ) 94.9 - 98.5 % , n = 391 ] and group II ( 94.6 % ; 95 % CI 92.3 - 96.9 , n = 386 ) . It was not possible to assess the outcome with certainty in the remaining 23 women . However , there were significantly more ongoing pregnancies in the women who received misoprostol than in those who received gemeprost ( nine versus one , P < 0.01 ) and in eight of these 10 women the gestation was > 49 days . Fewer women in group II required analgesia than in group I ( 48 versus 60 % , P < 0.001 ) although the number requesting opiate was similar in each group ( 6.9 versus 5.2 % , P > 0.4 ) . The incidence of nausea and vomiting after misoprostol ( 47.8 and 21.9 % respectively ) was higher ( P < 0.001 ) than after gemeprost ( 33.9 and 12 % respectively ) . ( ABSTRACT TRUNCATED AT 250 WORDS A study was undertaken to determine whether the combination of oral tamoxifen and moistened misoprostol administered vaginally was superior to that of placebo and moistened misoprostol administered vaginally for elective termination of early pregnancies . A clinical trial was conducted with a study group of 150 healthy women with pregnancies of < /=56 days gestational age who desired pregnancy termination . Subjects were r and omized to ingest either 20 mg of tamoxifen ( group 1 ) or placebo ( group 2 ) twice daily for 1 day , followed 48 h later by vaginal administration of 800 micrograms of saline-moistened misoprostol . This dose of misoprostol was repeated 24 h later and 8 days later if an abortion had not occurred . The main outcome measures were incidence of complete abortion , hemoglobin levels , duration of vaginal bleeding , and incidence of side effects . Complete abortion occurred in 709 ( 93.3 % ) in group 1 and 68 ( 90.7 % ) in group 2 . There were no differences in either group between earlier ( < /=49 days ) and later ( 50 - 56 days ) gestations . The mean duration of uterine bleeding was 7.9 days and 8.2 days in group 1 and group 2 , respectively . In group 1 , 94.3 % who aborted bled for < 14 days , and in group 2 , 95.6 % . No subject required a blood transfusion . There were no significant differences in side effects between the two groups . These data suggest that pretreatment with tamoxifen is not necessary when using moistened vaginal misoprostol for abortion of pregnancies of < /=56 days of gestation Objectives To compare the side effect profiles of regimens of oral and vaginal administration of misoprostol after a single oral dose of 200 mg of mifepristone and to investigate patients ' perceptions of medical abortion OBJECTIVE Mifepristone-misoprostol medical abortion has been approved in the United States since 2000 . U.S. providers have preferred to use vaginal misoprostol because of evidence that such a regimen is more effective in later gestations . Buccal administration of misoprostol may be equally effective and more acceptable to some women . METHODS This open-label , r and omized trial was conducted at two sites in Rochester , NY , and involved healthy women with pregnancies through 56 days since the last menstrual period ( LMP ) as indicated by sonogram . Women received mifepristone 200 mg orally and were r and omized to use 800 mug of misoprostol either buccally or vaginally 1 to 2 days later . They returned within 15 days for repeat sonogram . If the woman 's pregnancy had not been completely aborted by day 36 , a suction abortion was performed . The primary outcome was a complete abortion without surgical intervention . RESULTS Four hundred forty-two women were enrolled in the study , and complete data were available on 429 . The efficacy rate was 95 % ( 205/216 ) in the buccal group and 93 % ( 199/213 ) in the vaginal group ( chi(2)=0.43 , p=.51 ) . Nausea was the most commonly reported side effect , affecting 70 % in the buccal group and 62 % in the vaginal group . There were no differences in the satisfaction with the overall procedure between the buccal ( 92 % ) and the vaginal groups ( 95 % ) ( chi(2)=1.87 , p=.17 ) . CONCLUSION Buccal administration of misoprostol after low-dose mifepristone for medical abortion appears to be a highly effective and acceptable alternative compared with vaginal administration for medical abortion in pregnancies through 56 days LMP OBJECTIVE Our goal was to evaluate the pharmacokinetics and safety of methotrexate in doses of 50 mg/m2 and 60 mg/m2 in regimens for early abortion . STUDY DESIGN A r and omized controlled trial was performed in women requesting an abortion at < or = 49 days ' gestation . Twenty women were treated with intramuscular methotrexate 50 mg/m2 ( group 1 ) or 60 mg/m2 ( group 2 ) . Methotrexate levels were determined serially for the first 24 hours , then every 24 hours for 7 days . On the seventh day misoprostol 800 microg was administered vaginally . The misoprostol dose was repeated 24 hours later if abortion did not occur . RESULTS Complete abortion occurred in 9 of 10 ( 90 % , 95 % confidence interval 56 % to 100 % ) patients in group 1 and all 10 ( 100 % , 95 % confidence interval 69 % to 100 % ; p = 0.99 ) in group 2 . Methotrexate levels peaked within 1 to 2 hours and were nondetectable within 48 hours in all patients in group 1 and 72 hours in group 2 . Both the maximum concentration of methotrexate and the area under the curve were significantly greater for group 2 . Methotrexate clearance rates were 7.89 + /- 1.98 L/hr and 5.55 + /- 0.83 L/hr ( p = 0.003 ) , respectively . CONCLUSIONS The serum levels of intramuscular methotrexate with 50 mg/m2 and 60 mg/m2 regimens indicate that these are safe treatment doses . Methotrexate 50 mg/m2 intramuscularly has the same clearance rates when administered during pregnancy as in a nonpregnant state , and maximum concentrations do not reach sustained toxic levels Objectives 1 . To investigate the efficacy of 800 μg misoprostol ( a PGE1 analogue ) when administered to women pretreated with mifepristone for early pregnancy termination . 2 . To establish means of minimising gastrointestinal side effects by comparing two different misoprostol regimens . The impact of these regimens on blood pressure was investigated in a subgroup of patients Intramuscular methotrexate followed by vaginal misoprostol has been shown to be effective for abortion at < or = 49 days gestation . Oral dosing of the methotrexate may offer advantages over parenteral dosing . This pilot study was performed to evaluate if oral methotrexate would be effective when combined with vaginal misoprostol to effect abortion at < or = 49 days gestation . Twenty pregnant women were r and omized to receive methotrexate 25 mg or 50 mg followed 7 days later by misoprostol 800 micrograms vaginally . The misoprostol dose was repeated the next day if the abortion did not occur . Complete abortion occurred in all subjects in both groups within 20 days after the methotrexate . However , women in the 50 mg group passed the pregnancy within 24 hours of the first or second dose of methotrexate more often than women in the 25 mg group ( 80 % vs. 50 % , p = 0.35 ) . Vaginal bleeding lasted 12.1 + /- 3.1 days and 9.4 + /- 4.5 days in immediate success and delayed success patients , respectively . Oral methotrexate may be an effective alternative to intramuscular methotrexate in treatment regimens for nonsurgical abortion A total of 363 women undergoing legal abortion at < 63 days of amenorrhoea were allocated by a patient-centered , partially r and omized study design to undergo medical abortion ( using mifepristone 600 mg followed 48 h later by gemeprost 1 mg vaginal pessary ) or vacuum aspiration ( performed under general anaesthesia ) . The aim of the study was to compare the efficacy and complications of the two procedures . Main outcome measures included efficacy rates , medical complications within 21 days of abortion and unplanned family doctor consultation rates within 8 weeks following abortion . Sequelae such as pain , vaginal bleeding and recovery time were assessed by the change in haemoglobin level , the time taken to return to work or normal activity and the analgesic use . Results were gestation-related ; at 50 days of amenorrhoea there was little to choose between the two procedures . At 50 - 63 days of amenorrhoea medical abortion becomes more painful and less effective , whereas vacuum aspiration retains high tolerance and efficacy . Women who are unsure which method to use are likely to find vacuum aspiration more acceptable at longer gestations Objective To assess women 's acceptability , the efficacy and side effects of sublingual versus vaginal administration of misoprostol in combination with mifepristone for medical abortion up to 13 weeks of gestation BACKGROUND Prolonged vaginal bleeding is a common complaint after medical abortion . The effect of a 1 week course of daily oral misoprostol after medical abortion with mifepristone and misoprostol on the amount of post-abortal blood loss was studied . METHODS A total of 150 women ( gestation < or=63 days ) were r and omized to three groups using computer-generated tables . They received 200 mg oral mifepristone , followed 48 h later by 0.8 mg oral misoprostol and vaginal placebo in group A , and 0.8 mg vaginal misoprostol and oral placebo in groups B and C. In groups A and B , the women continued with oral misoprostol 0.4 mg twice daily on days 4 - 10 , while the women in group C took placebo . The actual blood loss was measured by the alkaline haematin method . RESULTS No significant difference in the median amount ( 82.8 , 94.7 and 88.5 ml for A , B and C respectively ) and duration ( 16 , 15 and 16 days respectively ) of vaginal bleeding was observed . The incidence of diarrhoea was significantly higher ( 66 , 55.1 and 12.5 % respectively ) in the groups with oral misoprostol after abortion . CONCLUSION A 1 week course of oral misoprostol ( 0.4 mg twice daily ) could not decrease the duration and amount of vaginal bleeding . Further studies with a larger sample size are needed to assess whether the complete abortion rate can be improved with this regimen Mifepristone was recently approved in the United States . Regimens with shorter intervals may be more acceptable . The objective of this study was to determine whether the oral route of misoprostol was as effective as the vaginal route of misoprostol 1 day after mifepristone . A prospect i ve , open-labeled , r and omized trial of healthy adult women up to 63 days pregnant and wanting a medical abortion were r and omized to use either two doses of oral misoprostol 400 microg taken 2 h apart or misoprostol 800 microg vaginally . Women self-administered misoprostol 1 day after taking one-third of the st and ard dose of mifepristone ( 200 mg ) orally . Women then returned to the clinic up to 5 days later for a repeat sonogram evaluation . A dose of vaginal misoprostol was administered to women with a continuing pregnancy who then returned 1 day later to Day 15 . The primary outcome measures were a complete medical abortion by the first or by the second follow-up visits . Surgical intervention was indicated for continuing pregnancy at the second follow-up visit , excessive bleeding , or persistent products of conception 5 weeks later . One thous and one hundred sixty-eight women were enrolled . Of the 1144 ( 98 % ) women who complied with their r and om assignment , two oral doses of misoprostol ( 800 microg total ) were 90 % effective at inducing an abortion by the first follow-up visit , compared with one dose of misoprostol by vagina of 97 % ( chi(2 ) = 23.95 , p = 0.001 ) . By the second follow-up visit , the complete abortion rate was 95 % for oral misoprostol and 99 % for vaginal misoprostol ( chi(2 ) = 21.76 , p = 0.001 ) . There were minimal differences in side effects . Women preferred the oral route . The trial demonstrated that although two doses of oral misoprostol were effective , the vaginal misoprostol was more effective at inducing an early medical abortion at 1 day after low-dose mifepristone , and the regimen could be extended to 63 days gestation OBJECTIVE To determine the best regimen for using misoprostol after methotrexate in medical abortion with respect to outcome and side effects . STUDY DESIGN In a cohort study , we compared vaginal misoprostol in one cohort of 134 women who used 800 micrograms dry tablets with 99 women who used 600 micrograms wet and 197 women who used 800 micrograms wet . These cohorts were compared with respect to outcome and side effects . RESULTS The " dry " group had fewer completed abortions by day 8 ( 55.2 % as compared to 69.7 % and 71.1 % , P = .008 ) but similar surgery rates . The dry group also had fewer side effects , especially fever and chills ( 4.5 % as compared to 25.3 % and 40.6 % , P = .0001 ) and vomiting ( 8.2 % as compared to 16.2 % and 20.3 % , P = .01 ) . CONCLUSION Of the three methods , the one consisting of 600 micrograms of wet misoprostol is the most effective for early completion of abortion and has the fewest side effects OBJECTIVE : To demonstrate equivalence between mifepristone 200 mg followed 6 to 8 hours later and 24 hours later by misoprostol 800 & mgr;g vaginally for abortion in women up to 63 days of gestation . METHODS : Mifepristone 200 mg was swallowed by 1,080 women after which they were r and omly assigned to self-administer misoprostol intravaginally 6 to 8 hours later ( group 1 ) or 23 to 25 hours later ( group 2 ) at home . Participants returned for an evaluation , including transvaginal ultrasonography , 7 ± 1 days after initiating treatment . Subjects who had not aborted were offered a second dose of misoprostol . All participants returned approximately 2 weeks after receiving mifepristone . Telephone contact was also attempted approximately 5 weeks after treatment . Treatment was considered a failure if a suction aspiration was performed for any indication . RESULTS : Complete abortion rates for groups 1 and 2 were 503 of 525 ( 95.8 % , 95 % confidence interval 93.7 % , 97.3 % ) and 521 of 531 ( 98.1 % , 95 % confidence interval 96.6 % , 99.1 % ) , respectively , which were statistically equivalent . Side effects were significantly more common after mifepristone administration for women in group 2 . Nausea , vomiting , and heavy bleeding were also significantly greater for women in group 2 after misoprostol treatment . Pain and subject acceptability were similar between groups . CONCLUSION : Mifepristone 200 mg followed 6 to 8 hours later by misoprostol 800 & mgr;g vaginally is as effective for abortion and has significantly fewer side effects as compared with regimens using a 24-hour dosing interval . Women receiving mifepristone and vaginal misoprostol for abortion can have the flexibility to administer the misoprostol as soon as 6 hours after using the mifepristone . LEVEL OF EVIDENCE : A multi-centre , r and omized trial was conducted to compare the efficacy and side-effects of two combination regimens of the antiprogestin RU 486 and the intramuscular PGE2 analogue sulprostone for termination of early pregnancy ( amenorrhoea up to 49 days ) . Women in the 3-day group ( n = 125 ) received 25 mg RU 486 twice daily for 3 days plus a single injection of 0.25 mg sulprostone in the morning of the third day of antiprogestin treatment . In the 4-day group ( n = 126 ) , RU 486 was given for 4 days and the sulprostone injection in the morning of the fourth day . Treatment outcome in the two groups was similar . Overall , 88.8 % had a complete abortion , 6.8 % an incomplete abortion and 2.4 % were treatment failures ; in the remaining 2 % treatment outcome could not be determined . Only three of the six women with treatment failure still had detectable fetal heart activity when the pregnancy was terminated by vacuum aspiration two weeks after the start of treatment . Five of the 17 interventions for incomplete abortion were carried out as emergency procedures because of heavy bleeding ; two of these five women were given a blood transfusion . The majority of the curettages ( 10/17 ) were performed in one centre . If the data from this centre and the women with undetermined treatment outcome were excluded , the rates for complete abortion , incomplete abortion and treatment failure in the remaining six centres were 93.6 , 3.7 and 2.7 % , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES To find out the optimal regimen of mifepristone in combination with misoprostol for termination of 10 - 16 week 's gestation . METHODS A r and omized comparative study in 2,007 women requesting medical abortion at 10 - 16 week 's gestation from 24 hospitals was conducted in Shanghai . Women were r and omly divided into 4 groups . In group I ( n = 511 ) women took mifepristone 75 mg orally per day for 2 days ( total dose 150 mg ) , and 48 hours later misoprostol 0.6 mg orally every 3 - 4 hours for 3 times ; group II ( n = 491 ) mifepristone 100 mg orally per day for 2 days ( total dose 200 mg ) and 48 hours later same dose of misoprostol were taken as in group I ; group III ( n = 519 ) same dose of mifepristone as in group I and 48 hours later misoprostol given vaginally every 12 hours for 3 times ; group IV ( n = 486 ) same dose of mifepristone as in group II and 48 hours later same dose of misoprostol vaginally as in group III . RESULTS The successful abortion rate from group I to group IV were 88.6 % , 89.4 % , 90.9 % and 94.0 % respectively . The successful abortion rate of group IV was higher than that in group I and II with significant differences ( P < 0.05 ) . The average dose of misoprostol by vaginal route in successful case was much lower than that by oral ( P < 0.01 ) , and the rate of side effects was much lower by vaginal too . CONCLUSION Mifepristone taken 200 mg orally plus misoprostol vaginally is an optimal method for termination of 10 - 16 week 's gestation BACKGROUND The most effective route and best interval between several doses of misoprostol to induce abortion have not been defined . Our aim was to assess the effects of the interval between multiple doses of misoprostol and the route of administration to terminate pregnancy . METHODS 2066 healthy pregnant women requesting medical abortion with 63 days or less of gestation were r and omly assigned within 11 gynaecological centres in six countries to the four treatment groups ( three doses of 0.8 mg misoprostol given sublingually at 3-h intervals , vaginally 3 h , sublingually 12 h , and vaginally 12 h ) , stratifying by gestational age . This was an equivalence trial with a 5 % margin of equivalence . The primary endpoints were efficacy of treatment to achieve complete abortion and to terminate pregnancy . The main efficacy analysis excluded women lost to follow-up . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N10531821 . FINDINGS Efficacy outcomes were analysed for 2046 women ( 99 % ) , excluding 20 lost to follow-up . Complete abortion rates at 2-week follow-up were recorded for 431 ( 84 % ) in the sublingual and for 434 ( 85 % ) women in the vaginal group when misoprostol was given at 3-h intervals ( difference 0.4 % , 95 % CI -4.0 to 4.9 , p=0.85 equivalence shown ) , and for 399 ( 78 % ) in the sublingual and for 425 ( 83 % ) in the vaginal 12-h groups ( 4.6 % , -0.2 to 9.5 , p=0.06 , equivalence not shown ) . In the 3-h groups , pregnancy continued in 29 ( 6 % ) women after sublingual and in 20 ( 4 % ) women after vaginal administration ( difference 1.8 % , 95 % CI -0.8 to 4.4 , p=0.19 , equivalence shown ) ; in the 12-h groups it continued in 47 ( 9 % ) after sublingual and in 25 ( 5 % ) after vaginal administration ( 4.4 % , 1.2 - 7.5 , p=0.01 , vaginal better than sublingual ) . Differences for complete abortion between intervals for sublingual and vaginal routes were 6 % ( 95 % CI 1.0 - 10.6 , p=0.02 , 3 h better than 12 h ) and 2 % ( -2.9 to 6.1 , p=0.49 , equivalence not shown ) , respectively ; for continuing pregnancies they were 4 % ( 0.4 - 6.8 , p=0.03 , 3 h better than 12 h ) and 1 % ( -1.5 to 3.5 , p=0.44 , equivalence shown ) , respectively . INTERPRETATION Administration interval can be chosen between 3 h and 12 h when misoprostol is given vaginally . If administration is sublingual , the intervals between misoprostol doses need to be short , but side-effects are then increased . With 12-h intervals , vaginal route should be used , whereas with 3-h intervals either route could be chosen This was a r and omized double-blind placebo-controlled trial to determine the effect of oral contraceptive ( OC ) pills taken immediately after medical abortion on the duration of bleeding and complete abortion rate . Two hundred women in the first 49 days of pregnancy were given 200 mg mifepristone orally followed by 400 microg misoprostol vaginally 48 h later . One day later , they were r and omized to receive either OC pills ( 30 microg of ethinyl oestradiol and 0.15 mg of levonorgestrel per tablet ) or placebo for 21 days . The complete abortion rates were 98 % in the OC group and 99 % in the placebo group . The median duration of bleeding was similar : 17 ( range : 5 - 57 ) days in the OC group and 16 ( range : 6 - 55 ) days in the placebo group . In the OC group there was a small but significant fall in the haemoglobin concentration by 14 days ( 5.3 g/dl ) after administration of mifepristone . The incidence of side-effects was similar in the two groups . We conclude that the use of OC pills does not decrease the duration of bleeding after medical abortion nor does it affect the abortion rate OBJECTIVE The primary objective of this study was to determine if buccal misoprostol was as effective as vaginal misoprostol in medical abortions . The secondary objectives were to compare side effects and acceptability . METHODS This was a r and omized controlled trial of 600 microg misoprostol by the buccal or vaginal routes used 3 to 6 days after 50 mg/m2 methotrexate . The participants were women presenting for abortion at 49 days or less gestation . The outcome measures were the number of women who had aborted by Day 8 , side effects and acceptability . RESULTS Day 8 completion rate was 53.5 % for the buccal route and 67.5 % for the vaginal route ( p = 0.012 ) . Side effects were similar in the two groups except that there was more burning with the buccal route . Overall acceptability and route acceptability were similar in the two groups . CONCLUSIONS When used after methotrexate for early abortion , the vaginal route for misoprostol is more effective and preferred to the buccal route OBJECTIVE To compare the safety and efficacy of early abortion by administration of methotrexate and misoprostol vs administration of misoprostol alone . DESIGN R and omized controlled trial . SETTING San Francisco ( Calif ) General Hospital . PATIENTS Pregnant women at 56 days ' gestation or less seeking elective abortion . Sixty-three women volunteered for the trial ; 61 completed the study and are included in the analysis . INTERVENTION Intramuscular administration of 50 mg of methotrexate per square meter of body surface area followed 3 days later by vaginal administration of 800 micrograms of misoprostol ( group 1 ) or the same dose of misoprostol given alone ( group 2 ) . The misoprostol dose was repeated 24 hours later if abortion had not occurred . MAIN OUTCOME MEASURES Successful abortion , duration of vaginal bleeding , side effects , and change in beta-human chorionic gonadotropin ( beta-hCG ) level . An abortion was considered successful if the pregnancy ended without requiring a surgical procedure . RESULTS Complete abortion occurred in 28 ( 90 % ) of 31 patients in group 1 and 14 ( 47 % ) of 30 patients in group 2 ( P < .001 ) . Seventeen ( 61 % ) of the 28 women in group 1 who aborted did so the same day as misoprostol administration ; vaginal bleeding lasted a mean ( + /- SD ) of 10 ( + /- 4 ) days , and beta-hCG level was less than or equal to 10 IU/L by a mean of 31 ( + /- 6 ) days after methotrexate administration . The 11 other women in group 1 who aborted did so after a mean delay of 29 ( + /- 11 ) days ; vaginal bleeding lasted 7 ( + /- 4 ) days , and beta-hCG level was less than or equal to 10 IU/L by a mean of 24 ( + /- 11 ) days after the abortion . There were three treatment failures in group 1 : two ongoing pregnancies ( 6 % ) and one incomplete abortion ( 3 % ) . For the 14 women with successful abortions in group 2 , vaginal bleeding lasted a mean of 10 ( + /- 6 ) days and beta-hCG level was less than or equal to 10 IU/L by mean of 39 ( + /- 18 ) days after the misoprostol . There were 16 treatment failures in group 2 : eight ongoing pregnancies ( 27 % ) , and eight incomplete abortions ( 27 % ) . Methotrexate side effects were minimal . Misoprostol side effects were diarrhea in 18 % and nausea and vomiting in 5 % . CONCLUSIONS Methotrexate and vaginal misoprostol are more effective than misoprostol alone . Both drugs are available throughout the United States , and both drugs are inexpensive . This combination may offer an alternative to the use of antiprogestin and prostagl and in for medical abortion BACKGROUND Gemeprost and misoprostol are two of the most widely used prostagl and ins in combination with mifepristone for medical abortion in early pregnancy . However , the efficacy and side-effects of those two drugs given vaginally have not been assessed in a r and omized trial . METHODS R and omized double-blind controlled trial involving 999 women undergoing an abortion at gestational age < or = 63 days who received either 0.5 mg gemeprost ( group I , n = 499 ) or 800 microg misoprostol ( group II , n = 500 ) vaginally approximately 48 h after taking 200 mg mifepristone by mouth . The rate of complete abortion and the side-effects were compared between the groups . RESULTS A total of 89 cases was excluded from full analysis of outcome because either they aborted after mifepristone alone ( n = 2 ) , had an ectopic pregnancy ( n = 1 ) , or because the outcome was uncertain as they failed to attend their follow-up appointment ( n = 86 ) . The rate of complete abortion was very high ( > 95 % ) in both groups but significantly higher after treatment with misoprostol than with gemeprost [ 436/453 ( 98.7 % ) versus 451/457 ( 96.2 % ) , P = 0.019 , difference 2.5 % , confidence interval 0.4 - 4.7 % ] and there were fewer ongoing pregnancies ( n = 1 versus n = 8 , P < 0.018 ) . Surgical intervention rose significantly with gestation in women who received gemeprost ( P < 0.03 ) but not with misoprostol . The incidence of side-effects such as diarrhoea ( 13.7 versus 16.4 % ) and vomiting ( 27.8 versus 29.7 % ) was similar in women who received misoprostol or gemeprost respectively , as was the duration and amount of bleeding . CONCLUSIONS ( i ) Both regimens using a reduced dose of mifepristone are highly effective methods of inducing abortion in early pregnancy ; ( ii ) vaginal misoprostol is the preferred prostagl and in because it is it is associated with fewer failures than low-dose gemeprost , particularly at gestation > or = 49 days OBJECTIVE To compare the antimetabolites methotrexate and 6-mercaptopurine as single-agent medical abortifacients using clinical and immunohistochemical analyses . METHODS Twenty-seven women with gestations less than 7 weeks from the last menstrual period ( LMP ) were r and omized to receive intramuscular methotrexate , 50 mg/m2 , or oral 6-mercaptopurine , 200 mg . Forty-six additional women received methotrexate after r and omization was discontinued . Women returned at 2-week intervals . Those without fetal cardiac activity were followed until complete abortion . Those with fetal cardiac activity were considered failures and underwent suction abortions . Tissue collected at the time of suction abortion was analyzed with the cell-proliferation immunohistochemical assay Ki-67 . RESULTS All 12 women in the 6-mercaptopurine group had fetal cardiac activity at follow-up and underwent suction abortion ; therefore , this arm of the study was discontinued . Six of the 61 women who received methotrexate had fetal cardiac activity at follow-up and also underwent suction abortion . Fetal cardiac activity was present after methotrexate in three of 55 women at less than 6 weeks from the LMP and in three of six between 6 and 7 weeks from the LMP ( P < .01 ) . Women who aborted after methotrexate started bleeding on day 19 ( st and ard deviation [ SD ] 7.8 ) , bled for 9 days ( SD 4.0 ) , and used minimal pain medications . Tissues exposed to methotrexate showed decreased Ki-67 activity compared with tissues exposed to 6-mercaptopurine ( P = .003 ) . CONCLUSION In oral doses of 200 mg , 6-mercaptopurine did not induce early abortion . A single intramuscular dose of methotrexate used without prostagl and ins induced abortion in most women at gestational ages of less than 6 weeks . Ki-67 activity was lower in a small sample of fetal tissues exposed to methotrexate than in tissues exposed to 6-mercaptopurine BACKGROUND Mifepristone in combination with prostagl and in has been used since 1988 for induction of early abortion . The aim of the present investigation was to assess the tolerance and efficacy of 600 mg . mifepristone orally followed by gemeprost 1 mg . vaginally either 24 hours ( group one ) or 48 hours ( group two ) later . METHODS Sixty-four healthy women applying for abortion within the first 8 weeks of pregnancy were r and omly allocated to one of the two treatment groups . Intrauterine pregnancy and gestational age were verified by ultrasonography . Symptoms after administration of mifepristone and gemeprost were recorded , and the patients observed at the hospital for at least three hours after prostagl and in-insertion . Blood sample s for blood group , hemoglobin , beta-chorion-gonadotrophin , aspartate-aminotransferase and creatinine were drawn . RESULTS Outcome was established by gynecological examination , the level of beta-hCG and ultrasonography , at visits one , two and if necessary three to four weeks later . Surgical curettage was performed in case of incomplete abortion , of which there were four in the 24-hour interval group and five in the 48-hour interval group with a success rate ( complete abortion ) of 55 out of 64 patients ( 86 % ) . CONCLUSIONS There was no difference in efficacy or side effects whether the prostagl and in was administered 24 or 48 hours after mifepristone intake , which suggests that the treatment period can be reduced from the conventional 48 hours Abortion was attempted in 39 women in early pregnancy ( less than 56 days amenorrhea ) with the progesterone antagonist RU486 alone ( 150 mg per day for 4 days ) or in combination with a PG analogue , 16,16-dimethyl-trans-delta 2-PGE1 ( Gemeprost ) in the form of a 1 mg vaginal pessary . Complete abortion was also attempted in 5 women who received RU486 together with 2 X 1 mg PG pessaries . Vaginal bleeding followed by complete abortion occurred in 18 of 19 women who received RU486 + 1 mg PG pessary as compared to only 12 of 20 women who received RU486 alone ( P less than 0.01 ) . All women who received RU486 + 2 mg Gemeprost had a complete abortion . The onset of crampy abdominal pain ( median : 3 vs 4 days ) and vaginal bleeding ( 3 vs 3 days ) was similar in the RU486 and RU486 + PG groups , respectively . Slightly less than half the patients in both groups had nausea and /or vomiting , but the incidence did not differ from that occurring prior to treatment . The mean duration ( range ) of vaginal bleeding [ RU486 alone : 10 ( 0,29 ) days and RU486 + PG : ( 5,34 ) days ] , and the measured blood loss [ RU486 : 53 ( 2,227 ) ml and RU486 + PG : 81 ( 32,222 ) ml ] did not differ significantly between the two treatments . It is concluded that the combination of RU486 and a single PG vaginal pessary is a highly effective means of inducing therapeutic abortion in early pregnancy and offers an alternative to surgery INTRODUCTION A growing body of literature has shown that misoprostol alone could be effective for early medical abortion . We evaluated seven potential regimens in women up to 56 days of gestation in order to potentially identify an optimal regimen . METHODS In phase I of the study , women requesting early abortion were r and omized to one of three misoprostol regimens ( 4x400 microg po every 3 h , 2x800 microg po every 6 h , 1x600 pv microg ) ; in phase II , women were r and omized to one of two regimens ( 2x800 microg po every 3 h , 1x800 pv microg ) . In phase III , we consecutively tested two regimens ( 800 microg pv wetted with saline repeated after 24 h if intact gestational sac , 2x800 microg pv wetted with saline ) to vali date previously published results . RESULTS Although most women experienced some side effects , all regimens were tolerable and acceptable . Five of the seven regimens result ed in complete abortion rates of 60 % or less . Only repeated doses of 800 microg pv misoprostol result ed in efficacy exceeding 60 % . DISCUSSION Misoprostol-alone abortion regimens using oral misoprostol are too ineffective for clinical use or further investigation . Regimens with repeated dosing of misoprostol 800 microg pv warrant further study to find the optimal treatment protocol A prospect i ve trial was conducted including 300 pregnant women seeking elective abortion to evaluate the safety and efficacy of methotrexate and misoprostol for abortion at < or = 56 days gestation . Subjects received methotrexate 50 mg/ m2 intramuscularly followed 7 days later by misoprostol 800 micrograms vaginally . The misoprostol dose was repeated the next day if the abortion did not occur . Outcome measures included successful abortion ( complete abortion without requiring a surgical procedure ) , duration of vaginal bleeding , and side effects . Complete abortion occurred in 263/ 300 ( 87.7 % , 95 % CI 83.4 , 91.2 % ) patients . The complete abortion rate was higher for early gestations : 183/202 ( 90.6 % , 95 % CI 85.7 , 94.2 % ) at < or = 49 days gestation , and 80/98 ( 81.6 % , 95 % CI 72.5 , 88.7 % ) from 50 - 56 days gestation ( p = 0.038 ) . Abortion occurred in the 24 hours following the initial or repeat misoprostol dose ( immediate success ) in 65.0 % ; the remaining 22.7 % of women who aborted did so after a delay of 23.6 + /- 9.1 ( mean + /- st and ard deviation ) days . Vaginal bleeding lasted 14 + /- 7 days and 11 + /- 9 days in immediate success and delayed success patients , respectively . Overall , 69.7 % , 87.7 % , and 91.7 % of patients had passed the pregnancy by 14 , 28 , and 35 days , respectively , after receiving methotrexate . Methotrexate and misoprostol side effects were minimal . This treatment regimen offers an alternative to surgical abortion or the use of antiprogestins and prostagl and in for medical abortion Three different regimens of RU 486 , a progesterone receptor blocking agent , were compared for their ability to terminate early human pregnancy . One-hundred-fifty-three healthy women with a gestational length less than 49 days from the last menstrual period were recruited to the study and r and omly allocated to one of three treatment regimens : 1 ) RU 486 10 mg x 2 for seven days ; 2 ) RU 486 25 mg x 2 for seven days ; or 3 ) RU 486 50 mg x 2 for seven days . No significant difference in efficacy was seen between the three dose regimens . Treatment with 10 mg x 2 x VII result ed in 73 per cent complete abortions , 25 mg x 2 x VII in 66 per cent and 50 mg x 2 x VII in 64 per cent complete abortions . Response to treatment , measured as reported onset of bleeding and passage of products of conception , however , occurred significantly later on the 10 mg x 2 regimen than on the other two dose regimens . In each treatment group , women who subsequently aborted completely had significantly lower pretreatment levels of hCG than women with incomplete abortion or continuing pregnancy . The treatment was well tolerated by the women and except for one woman who experienced a profound bleeding necessitating a blood transfusion , no serious side effects were seen OBJECTIVE : Mifepristone and oral misoprostol are typically used for medical abortion in women up to 49 days of gestation , with a 36- to 48-hour interval between the medications . Alternative routes of misoprostol administration allow for use beyond 49 days of gestation . We design ed this r and omized , noninferiority trial to compare the efficacy , adverse effects , and acceptability of misoprostol 800 mcg vaginally administered simultaneously with , or 24 hours after , mifepristone 200 mg orally for abortion in women up to 63 days of gestation . METHODS : The 1,128 participants swallowed mifepristone 200 mg and were then r and omized to self-administer misoprostol intravaginally immediately in the office ( group 1 ) or 24 hours later at home ( group 2 ) . Subjects returned for an evaluation , including transvaginal ultrasonography , 7±1 days after initiating treatment . Women who had not aborted were offered a second dose of misoprostol and returned for another evaluation in approximately 1 week . A phone contact was also attempted approximately 5 weeks after treatment . Treatment was considered a failure if a suction aspiration was performed for any indication . RESULTS : The complete abortion rate for group 1 ( 95.1 % , 95 % confidence interval [ CI ] 93.0–96.8 % ) was statistically noninferior to that for group 2 ( 96.9 % , 95 % CI 95.1–98.2 % ) ( P=.003 ) . The abortion rates between groups did not significantly differ by gestational age . Adverse effects were mostly similar , although nausea , diarrhea , and warmth or chills were significantly more common in group 1 . CONCLUSION : Mifepristone 200 mg and misoprostol 800 mcg vaginally used simultaneously is as effective for abortion as compared with regimens using a 24-hour dosing interval . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00269568 LEVEL OF EVIDENCE : OBJECTIVES To compare the abortifacient efficacy and side effects of three doses of the antiprogestin mifepristone plus prostagl and in for termination of early pregnancy . DESIGN R and omised , double blind multicentre trial . SETTING 11 departments of obstetrics and gynaecology and of family planning , mostly in university hospitals , in seven countries . SUBJECTS 1182 women with an early pregnancy ( menstrual delay of 7 - 28 days ) requesting abortion . INTERVENTIONS Single doses of 200 mg , 400 mg , or 600 mg mifepristone followed , 48 hours later , by vaginal pessary of 1 mg of the prostagl and in E1 analogue gemeprost . MAIN OUTCOME MEASURES Outcome of treatment ; duration and subjective amount of menstrual bleeding ; side effects and complications ; and concentrations of haemoglobin . RESULTS Outcome was similar with the three doses of mifepristone . Of the 1151 women with known outcome , 95.5 % had a complete abortion ( 364 ( 93.8 % ) of those given 200 mg mifepristone , 368 ( 94.1 % ) of those given 400 mg , and 367 ( 94.3 % ) of those given 600 mg ) , 3.7 % had an incomplete abortion ( 14 ( 3.6 % ) , 15 ( 3.8 % ) , and 14 ( 3.6 % ) ) , 0.3 % had a missed abortion ( three ( 0.8 % ) , one ( 0.3 % ) , and none ) , and 0.4 % had a continuing live pregnancy ( two ( 0.5 % ) , two ( 0.5 % ) , and one ( 0.3 % ) ) . Of the 43 women who had incomplete abortion , 23 underwent emergency uterine curettage ( usually for haemostatic purpose s ) and three of these women were given a blood transfusion . The numbers of reported complaints , bleeding patterns , and changes in blood pressure and haemoglobin concentrations were similar with the three treatments . CONCLUSIONS For termination of early pregnancy a single dose of 200 mg mifepristone is as effective as the currently recommended dose of 600 mg when used in combination with a vaginal pessary of 1 mg gemeprost OBJECTIVE This study was undertaken to compare oral to injected methotrexate with respect to effectiveness , side effects , and acceptability . STUDY DESIGN One hundred women in an urban primary care practice were r and omly assigned in phase 1 to receive 50 mg/m(2 ) methotrexate by either the oral or the injected route . In phase 2 another 87 women were allowed to choose between the oral and injected routes . In both phases and in all groups the methotrexate was followed 5 to 7 days later by misoprostol administered vaginally by the patient . The main outcome was the success rate ( the number whose pregnancies aborted without surgery ) ; other outcomes included side effects and acceptability . RESULTS There were no differences in rates of success , side effects , or acceptability between groups receiving oral and injected methotrexate . Among the women in phase 2 the oral form was chosen by 57.5 % . CONCLUSION This study indicates that for medical abortions induced with methotrexate and misoprostol it is possible to offer both the oral and injected routes of methotrexate without sacrificing efficacy and that about half of the women offered a choice will choose the oral route It has been shown that the antiprogestin RU 486 ( mifepristone ) increases the sensitivity of the early pregnant human uterus to the stimulatory action of synthetic prostagl and in E ( PGE ) analogues . To examine if RU 486 also increases uterine sensitivity to the naturally occurring PGE2 given orally , two investigative approaches were used in the present studies : ( i ) direct registration of uterine contractions before and after PGE2 administration in untreated and RU 486-treated early pregnant women ; and ( ii ) a double-blind , r and omized , controlled efficacy trial involving treatment of pregnant women ( amenorrhoea of less than or equal to 49 days ) with RU 486 ( 25 mg twice daily for 4 days ) and PGE2 ( 1 mg once or twice ) or placebo on the last day of RU 486 treatment . The results indicate that oral PGE2 at the doses employed had little or no stimulatory effect on uterine contractility and that it did not improve the rate of complete abortion achieved with RU 486 alone . Overall , 25 of 42 women ( 59 % ) had a complete abortion , 15 women ( 36 % ) did not abort and the remaining two had incomplete abortions . Women with complete abortions had significantly lower pretreatment levels of progesterone and a longer duration of induced bleeding than those who did not abort . Thus oral PGE2 , when given in clinical ly acceptable doses , is not a suitable alternative to synthetic PGE analogues for use in combination with RU 486 for termination of early pregnancy |
10,395 | 32,270,403 | For the outcomes of symptom resolution and complications in adult women with UTI , evidence favors antibiotics over NSAIDs .
| Amid growing antimicrobial resistance , there is an increasing focus on antibiotic stewardship efforts to reduce inappropriate antibiotic prescribing .
In this context , novel approaches for treating infections without antibiotics are being explored .
One such strategy is the use of non-steroidal anti-inflammatory drugs ( NSAIDs ) for uncomplicated urinary tract infections ( UTIs ) .
Therefore , we conducted a systematic review of r and omized controlled trials to evaluate the rates of symptom resolution and infectious complications in adult women with uncomplicated UTIs treated with antibiotics versus NSAIDs . | Study question Can treatment of the symptoms of uncomplicated urinary tract infection ( UTI ) with ibuprofen reduce the rate of antibiotic prescriptions without a significant increase in symptoms , recurrences , or complications ? Methods Women aged 18 - 65 with typical symptoms of UTI and without risk factors or complications were recruited in 42 German general practice s and r and omly assigned to treatment with a single dose of fosfomycin 3 g ( n=246 ; 243 analysed ) or ibuprofen 3 × 400 mg ( n=248 ; 241 analysed ) for three days ( and the respective placebo dummies in both groups ) . In both groups additional antibiotic treatment was subsequently prescribed as necessary for persistent , worsening , or recurrent symptoms . The primary endpoints were the number of all courses of antibiotic treatment on days 0 - 28 ( for UTI or other conditions ) and burden of symptoms on days 0 - 7 . The symptom score included dysuria , frequency/urgency , and low abdominal pain . Study answer and limitations The 248 women in the ibuprofen group received significantly fewer course of antibiotics , had a significantly higher total burden of symptoms , and more had pyelonephritis . Four serious adverse events occurred that lead to hospital referrals ; one of these was potentially related to the trial drug . Results have to be interpreted carefully as they might apply to women with mild to moderate symptoms rather than to all those with an uncomplicated UTI . What this paper adds Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics . Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms . Funding , competing interests , data sharing German Federal Ministry of Education and Research ( BMBF ) No 01KG1105 . Patient level data are available from the corresponding author . Patient consent was not obtained but the data are anonymised and risk of identification is low . Trial registration No Clinical TrialGov Identifier NCT01488955 Background Uncomplicated lower urinary tract infections ( UTI ) are usually treated with antibiotics . However , there is little evidence for alternative therapeutic options . This pilot study was set out 1 ) to make a rough estimate of the equivalence of ibuprofen and ciprofloxacin for uncomplicated urinary tract infection with regard to symptom resolution , and 2 ) to demonstrate the feasibility of a double-blind , r and omized controlled drug trial in German general practice s. Methods We performed a double-blind , r and omized controlled pilot trial in 29 German general practice s. Eighty otherwise healthy women aged 18 to 85 years , presenting with at least one of the main UTI symptoms dysuria and frequency and without any complicating factors , were r and omly assigned to receive either ibuprofen 3 × 400 mg oral or ciprofloxacin 2 × 250 mg ( + 1 placebo ) oral , both for three days . Intensity of main symptoms - dysuria , frequency , low abdominal pain - was recorded at inclusion and after 4 , 7 and 28 days , scoring each symptom from 0 ( none ) to 4 ( very strong ) . The primary endpoint was symptom resolution on Day 4 . Secondary outcomes were the burden of symptoms on Days 4 and 7 ( based on the sum score of all symptoms ) , symptom resolution on Day 7 and frequency of relapses . Equivalence margins for symptom burden on Day 4 were pre-specified as + /- 0.5 sum score points . Data analysis was done by intention to treat and per protocol . R and omization was carried out on patient level by computer programme in blocks of six . Results Seventy-nine patients were analyzed ( ibuprofen n = 40 , ciprofloxacin n = 39 ) . On Day 4 , 21/36 ( 58.3 % ) of patients in the ibuprofen-group were symptom-free versus 17/33 ( 51.5 % ) in the ciprofloxacin-group . On Day 4 , ibuprofen patients reported fewer symptoms in terms of total sum score ( 1 ; SD 1,42 ) than ciprofloxacin patients ( 1,3 ; SD 1,9 ) , difference -0,33 ( 95 % CI ( -1,13 to + 0,47 ) ) , PP ( per protocol ) analysis . During Days 0 and 9 , 12/36 ( 33 % ) of patients in the ibuprofen-group received secondary antibiotic treatment due to ongoing or worsening symptoms , compared to 6/33 ( 18 % ) in the ciprofloxacin-group ( non significant ) . A total of 58 non-serious adverse events were reported , 32 in the ibuprofen group versus 26 in the ciprofloxacin group ( non significant ) . Conclusions Our results support the assumption of non-inferiority of ibuprofen compared to ciprofloxacin for treatment of symptomatic uncomplicated UTI , but need confirmation by further trials . Trial registration Trial registration number : IS RCT N00470468See Commentary http://www.biomed central .com/1471 - Objectives To explore the views of women with urinary tract infection on the acceptability of different strategies for managing the infection , including delayed use of antibiotics , and the cause of infection . Design Qualitative interview study with semistructured one to one interviews within a r and omised controlled trial of different management strategies . Analysis drew on some of the principles of constant comparison to generate key themes grounded in reported experiences and underst and ings . Setting Seven general practice s across four counties in southern Engl and . Participants 21 women presenting to general practice s who were taking part in the larger trial . Results Women preferred not to take antibiotics and were open to alternative management approaches . With a strategy of “ antibiotic delay ” some women felt a lack of validation or that they were not listened to by their general practitioner . Women attributed urinary tract infection to lifestyle habits and behaviours , such as poor hygiene , general “ negligence , ” and even a “ penalty of growing old . ” Conclusion A clear acknowledgment of women ’s triggers to consult is needed . If women are asked to delay taking antibiotics , the clinician must address the particular worries that women might have and explain the rationale for not using antibiotics immediately OBJECTIVES To determine the clinical effectiveness and cost-effectiveness of topical mometasone in children with bilateral otitis media with effusion ( OME ) . DESIGN A double-blind r and omised placebo-controlled trial with an intention to treat analysis ; the 10.6 % of patients lost to follow-up at 1 month were censored in the analysis . SETTING 76 Medical Research Council General Practice Research Framework practice s throughout the UK between 2004 and 2007 . PARTICIPANTS A sample of 217 children aged 4 - 11 years was selected from those presenting to their GP with one or more episodes of otitis media or ear-related problems in the previous 12 months whom the research nurse confirmed had bilateral glue ear using microtympanometry ( B B or B C2 types using a modified Jerger classification ) at r and omisation . INTERVENTIONS Mometasone 50 micrograms in each nostril or placebo spray once daily for 3 months . MAIN OUTCOME MEASURES The primary outcome was the proportions of children cleared of OME assessed by tympanometry at 1 month . Secondary outcomes included clearance at 3 months and 9 months ; adverse events ; OM8 - 30 scores ( a functional health status responsive disease-specific measure ) ; hearing loss ; days with otalgia ; cost-effectiveness ; and health utilities . RESULTS Of the topical steroid group , 40.6 % ( 39/96 ) demonstrated tympanometric clearance ( C1 or A type ) in one or both ears at 1 month , compared with 44.9 % ( 44/98 ) of the placebo group . The absolute risk reduction at 1 month was -4.3 % ( 95 % CI -18.05 % to 9.26 % ) ; the odds ratio ( OR ) was 0.84 ( 95 % CI 0.48 to 1.48 ) . Four covariates were pre-specified for inclusion in logistic regression analysis : age as a continuous variable ( p = 0.94 ) , season ( p = 0.70 ) , atopy ( p = 0.61 ) and clinical severity ( p = 0.006 ) . The adjusted OR ( AOR ) at 1 month for the main outcome was 0.93 ( 95 % CI 0.50 to 1.75 ) . Secondary analysis at 3 months showed 58.1 % of the steroid group had resolved and 52.3 % of the placebo group , AOR 1.45 ( 95 % CI 0.74 to 2.84 ) . At 9 months 55.6 % of the treated group remained clear in at least one ear and 65.3 % of the placebo group , AOR 0.82 ( 95 % CI 0.39 to 1.75 ) . Adverse events ( although relatively minor ) occurred in 7 - 22 % of children and included nasal stinging , epistaxis , dry throat and cough . The OM8 - 30 scores ( p = 0.55 ) reported hearing difficulty ( p = 0.08 ) , and days with otalgia ( p = 0.46 ) were not significantly different between groups at 3 months . The economic evaluation found the active treatment arm to be dominated by placebo , accruing slightly ( but not significantly ) higher costs and fewer quality -adjusted life-years ( QALYs ) , with a 24.2 % probability that topical steroids are a cost-effective use of NHS re sources at a ceiling ratio of 20,000 pounds per QALY gained . CONCLUSIONS Use of topical intranasal corticosteroids is very unlikely to be a clinical ly effective treatment for OME ( glue ear ) in the primary care setting . TRIAL REGISTRATION Current Controlled Trials IS RCT N38988331 Purpose Non-steroidal anti-inflammatory drugs ( NSAIDs ) are frequently prescribed or used as self-medication in cases of community-acquired pneumonia ( CAP ) . Nevertheless , the consequences of such medication on the risk of pleuroparenchymal complications are not well known . The aim was to investigate whether exposure to NSAIDs prior to hospital admission among patients suffering from CAP is associated with the development of pleural complications or a lung abscess . Methods All consecutive non-immunocompromised patients with CAP and admitted to a university hospital were prospect ively included ( 2-year period ) . The risk of pleuropulmonary complications was analyzed according to previous exposure to NSAIDs . Results Of the 221 included patients , 40 ( 18.1 % ) had developed a pleuropulmonary complication . NSAIDs intake prior to admission was reported for 24 patients ( 10.9 % ) who were younger ( 50.6 ± 18.5 vs. 66.5 ± 16.4 years ; p = 0.001 ) , had less comorbidities ( 60 vs. 25.1 % ; p = 0.001 ) , had a longer duration between the first symptoms of CAP and the start of an antibiotic therapy ( 6.1 ± 7.6 vs. 2.8 ± 3.8 days ; p = 0.001 ) , and who had a higher incidence of pleuropulmonary complications ( 33.3 vs. 16.2 % ; p = 0.048 ) . In multivariate analyses , two factors were independently associated with the development of pleuroparenchymal complications : NSAIDs intake [ Odds Ratio ( OR ) = 2.57 [ 1.02–6.64 ] ; p = 0.049 ] and alcohol abuse ( OR = 2.68 [ 1.27–5.69 ] ; p = 0.01 ) . Conclusions Our findings suggest that NSAIDs , often taken by young and healthy patients , may worsen the course of CAP with delayed therapy and a higher rate of pleuropulmonary complications Background Women presenting with symptoms of acute uncomplicated urinary tract infection ( UTI ) are often prescribed antibiotics . However , in 25 to 50 % of symptomatic women not taking antibiotics , symptoms recover spontaneously within one week . It is not known how many women are prepared to delay antibiotic treatment . We investigated how many women presenting with UTI symptoms were willing to delay antibiotic treatment when asked by their general practitioner ( GP ) . Methods From 18 April 2006 until 8 October 2008 , in a prospect i ve cohort study , patients were recruited in 20 GP practice s in and around Amsterdam , the Netherl and s. Healthy , non-pregnant women who contacted their GP with painful and /or frequent micturition for no longer than seven days registered their symptoms and collected urine for urinalysis and culture . GPs were requested to ask all patients if they were willing to delay antibiotic treatment , without knowing the result of the culture at that moment . After seven days , patients reported whether their symptoms had improved and whether they had used any antibiotics . Results Of 176 women , 137 were asked by their GP to delay antibiotic treatment , of whom 37 % ( 51/137 ) were willing to delay . After one week , 55 % ( 28/51 ) of delaying women had not used antibiotics , of whom 71 % ( 20/28 ) reported clinical improvement or cure . None of the participating women developed pyelonephritis . Conclusions More than a third of women with UTI symptoms are willing to delay antibiotic treatment when asked by their GP . The majority of delaying women report spontaneous symptom improvement after one week Objective . To analyse associations between symptoms and bacteriuria in uncomplicated lower urinary tract infection in women ( LUTIW ) and to evaluate outcome of therapy with three different regimens of pivmecillinam or placebo . Design . Prospect i ve , multicentre , r and omized , double-blind , and placebo-controlled therapy study . Symptoms registered at inclusion , during therapy and at follow-up visits after 8–10 and 35–49 days . Significant bacteriuria defined according to current European guidelines . Setting . A total of 18 primary healthcare centres in northern Sweden . Subjects . Women aged 18 years and above with symptoms of urgency , dysuria , supra pubic or loin pain . Main outcome measures . Symptoms and bacteriuria at inclusion and course of symptoms , bacteriuria , and their combinations during and post-therapy . Results . At inclusion , no associations or significant differences were found between symptom scores and bacteriuria , bacterial counts , or species . The 884 patients ( 77 % ) with significant bacteriuria were followed up . All pivmecillinam therapies were superior to placebo ( p < 0.001 ) . From day six until first follow-up , the mean values of all symptoms were higher and the bacteriological cure was lower at first follow-up in the three days ( 84 % ) compared with the seven days regimens ( 93–94 % , p < 0.001 ) . At final follow-up clinical cure was similar in all pivmecillinam regimens ( 65–72 % ) as was bacteriological cure ( 83–89 % ) . Pivmecillinam had few low to mild adverse reactions , comparable to placebo . Conclusions . Symptoms are not conclusive for diagnosis of LUTIW . Pivmecillinam therapies are superior to placebo and seven days regimens are more efficient than three days . Pivmecillinam 200 mg × 2 × 7 days is recommended as a first-line therapy for LUTIW Objective To investigate whether symptomatic treatment with non-steroidal anti-inflammatory drugs ( NSAIDs ) is non-inferior to antibiotics in the treatment of uncomplicated lower urinary tract infection ( UTI ) in women , thus offering an opportunity to reduce antibiotic use in ambulatory care . Design R and omised , double blind , non-inferiority trial . Setting 17 general practice s in Switzerl and . Participants 253 women with uncomplicated lower UTI were r and omly assigned 1:1 to symptomatic treatment with the NSAID diclofenac ( n=133 ) or antibiotic treatment with norfloxacin ( n=120 ) . The r and omisation sequence was computer generated , stratified by practice , blocked , and concealed using sealed , sequentially numbered drug containers . Main outcome measures The primary outcome was resolution of symptoms at day 3 ( 72 hours after r and omisation and 12 hours after intake of the last study drug ) . The prespecified principal secondary outcome was the use of any antibiotic ( including norfloxacin and fosfomycin as trial drugs ) up to day 30 . Analysis was by intention to treat . Results 72/133 ( 54 % ) women assigned to diclofenac and 96/120 ( 80 % ) assigned to norfloxacin experienced symptom resolution at day 3 ( risk difference 27 % , 95 % confidence interval 15 % to 38 % , P=0.98 for non-inferiority , P<0.001 for superiority ) . The median time until resolution of symptoms was four days in the diclofenac group and two days in the norfloxacin group . A total of 82 ( 62 % ) women in the diclofenac group and 118 ( 98 % ) in the norfloxacin group used antibiotics up to day 30 ( risk difference 37 % , 28 % to 46 % , P<0.001 for superiority ) . Six women in the diclofenac group ( 5 % ) but none in the norfloxacin group received a clinical diagnosis of pyelonephritis ( P=0.03 ) . Conclusion Diclofenac is inferior to norfloxacin for symptom relief of UTI and is likely to be associated with an increased risk of pyelonephritis , even though it reduces antibiotic use in women with uncomplicated lower UTI . Trial registration Clinical Trials.gov NCT01039545 BACKGROUND Nonsteroidal antiinflammatory drugs ( NSAIDs ) are commonly used as antipyretics and analgesics and may affect the host response to acute infection . We investigated the potential influence of NSAIDs on the presentation and short-term outcomes of nonimmunocompromised in patients with community-acquired pneumonia ( CAP ) admitted to the ICU . METHODS All consecutive patients with CAP admitted to the ICU or step-down unit of a university hospital during a 4-year period were prospect ively included , except when receiving long-term NSAIDs or steroids . Drug exposures , presentation , and hospital course were recorded . RESULTS Of the 90 patients included , 32 ( 36 % ) had taken NSAIDs prior to hospital referral . Compared with nonexposed patients , they were younger and had fewer comorbidities but similar severity of disease at presentation , despite a longer duration of symptoms before referral . However , they more often developed pleuropulmonary complications , such as pleural empyema and lung cavitation ( 37.5 % vs 7 % ; P = .0009 ) , and had a trend to more-invasive disease , with a higher frequency of pleural empyema ( 25 % vs 5 % , P = .014 ) and bacteremia , especially in those not having received concomitant antibiotics ( 69 % vs 27 % , P = .009 ) . Nevertheless , the patients in the NSAID group had no more severe systemic inflammation or remote organ dysfunction . In multivariable analyses , NSAID exposure was independently associated with the occurrence of pleuropulmonary complications ( OR , 8.1 ; 95 % CI , 2.3 - 28 ) . CONCLUSIONS Our findings suggest that NSAID exposure at the early stage of CAP is associated with a more complicated course but a blunted systemic response , which may be associated with a delayed diagnosis and a protracted course BACKGROUND Uncomplicated urinary tract infections ( UTIs ) are the most common bacterial infections among women presenting to primary care causing rapidly increasing strains of resistant bacteria to the growing antibiotic industry . Restricting antibiotics to necessary indications is the only solution . The objectives of the study were to compare the efficacy of symptomatic treatment vs antibiotic in patients with uncomplicated UTI , in terms of individual symptom score , i.e. , frequency , urgency , dysuria , supra pubic pain scores and total symptoms scores . METHODS A r and omized control trial ( RCT ) in 100 women ( 15 - 50 years ) with symptoms of urinary frequency , urgency , dysuria and pain supra pubic region , associated with uncomplicated UTI , at Urology department , AMI , Abbottabad . Two treatment strategies were compared in uncomplicated UTI patient ) . Patients were r and omized to antibiotic or symptomatic treatment groups on consecutive non-probability basis ( 50 in each group ) given for 05 days . Efficacy of medications was assessed by comparing pre and post treatment symptom scores along with the post treatment scores of both groups compared to see statistical significance of difference by independent sample s t-test . RESULTS There was a statistically significant difference in symptoms improvement in both treatment arms of all scores , i.e. , p-value=0.000 . Whereas only dysuria score was able to show a statistically significance of difference in post Rx scores comparison of both groups , p-value=0.004 . CONCLUSIONS Symptomatic treatment is not inferior to antibiotic treatment when proper patient selection is undertaken , result ing in decreased need for unnecessary antibiotics use Background Although uncomplicated urinary tract infections ( UTIs ) are often self-limiting , most patients will be prescribed antibiotic treatment . We assessed whether treatment with ibuprofen was non-inferior to pivmecillinam in achieving symptomatic resolution by day 4 , with a non-inferiority margin of 10 % . Methods and findings This was a r and omized , controlled , double-blind non-inferiority trial . We recruited patients from 16 sites in a general practice setting in Norway , Sweden , and Denmark . Non-pregnant women aged 18–60 years presenting with symptoms of uncomplicated UTI were screened for eligibility from 11 April 2013 to 22 April 2016 . Patients with informed consent were r and omized ( 1:1 ratio ) to treatment with either 600 mg ibuprofen or 200 mg pivmecillinam 3 times a day for 3 days . The patient , treating physician , and study personnel were blinded to treatment allocation . The primary outcome was the proportion of patients who felt cured by day 4 , as assessed from a patient diary . Secondary outcomes included the proportion of patients in need of secondary treatment with antibiotics and cases of pyelonephritis . A total of 383 women were r and omly assigned to treatment with either ibuprofen ( n = 194 , 181 analyzed ) or pivmecillinam ( n = 189 , 178 analyzed ) . By day 4 , 38.7 % of the patients in the ibuprofen group felt cured versus 73.6 % in the pivmecillinam group . The adjusted risk difference with 90 % confidence interval was 35 % ( 27 % to 43 % ) in favor of pivmecillinam , which crossed the prespecified non-inferiority margin . Secondary endpoints were generally in favor of pivmecillinam . After 4 weeks ’ follow-up , 53 % of patients in the ibuprofen group recovered without antibiotic treatment . Seven cases of pyelonephritis occurred , all in the ibuprofen group , giving a number needed to harm of 26 ( 95 % CI 13 to 103 ) . Five of these patients were hospitalized and classified as having serious adverse events ; 2 recovered as out patients . A limitation of the study was the extensive list of exclusion criteria , eliminating almost half of the patients screened . We did not register symptoms in the screening process ; hence , we do not know the symptom burden for those who declined to participate . This might make our results less generalizable . Conclusions Ibuprofen was inferior to pivmecillinam for treating uncomplicated UTIs . More than half of the women in the ibuprofen group recovered without antibiotics . However , pyelonephritis occurred in 7 out of 181 women using ibuprofen . Until we can identify those women who will develop complications , we can not recommend ibuprofen alone as initial treatment to women with uncomplicated UTIs . Trial registration Clinical Trials.gov NCT01849926 EU Clinical Trials Register ( EU-CTR ) , EudraCT Number 2012 - 002776 - BACKGROUND Urinary tract infections ( UTIs ) are very common and have been treated with apparent success with antimicrobials for many years . However , there is a paucity of placebo-controlled clinical trials . AIM To measure the symptomatic and bacteriological short-term effect of nitrofurantoin treatment versus placebo , in the treatment of uncomplicated UTI in adult non-pregnant women . DESIGN OF STUDY R and omised placebo-controlled trial in general practice . SETTING Non-pregnant women , aged between 15 and 54 years old , consulting a general practitioner for symtoms suggestive of uncomplicated lower UTI and with pyuria ( positive for leucocyte esterase test ) . METHOD A dipslide was inoculated in first-void midstream urine and sent for examinion . The patients were r and omised to receive nitrofurantoin 100 mg or placebo four times daily for three days . After three , seven , and 14 days a new dipslide was inoculated and symptoms of UTI were checked or improvement of symptoms and bacteriuria . RESULTS Of 166 women consulting with symptoms suggestive for UTI , 78 had pyuia and agreed to participate in the study ( the clinical ly suspected UTI group ) ; of these , 40 received nitrofurantoin and 38 received placebo . The result for combined symptomatic improvement and cure after three days was 27/35 in the nitrofurantoin group and 19/35 in the placebo group ( c2 with Yates ' correction P = 0.008 ; number needed to treat [ NNT ] = 4.4 , 95 % confidence interval [ CI ] = 2.3 to 79 ) . After seven days , combined improvement and cure was observed in 30/34 and 17/33 respectively ( P = 0.003 , NNT = 2.7 , 95 % CI = 1.8 to 6.0 ) . At inclusion , 56 women had bacteriuria of > or = 10(5 ) CFU/ml ( the bacteriologically proven UTI group ) . Of these , 29 received nitrofurantoin and 27 received placebo . After three days the bacteriological cure was 21/26 in the treatment group , compared with 5/25 in the placebo group ( P < 0.001 ; NNT = 1.6 , 95 % CI= 1.2 to 2.6 ) . After seven days the bacteriological cure rate was 17/23 in the intervention group and 9/22 in the placebo group ( P = 0.05 , NNT = 3 , 95 % CI = 1.7 to 17 ) . CONCLUSION In women with bacteriologically proven UTI , nitrofurantoin was significantly more effective than placebo in achieving bacteriological cure and symptomatic relief in just three days ; this was still present after seven days . In patients with clinical ly suspected UTI the symptomatic effect was statistically significant BACKGROUND Uncomplicated bacterial community-acquired urinary tract infection is among the more common infections in outpatient practice . The resistance level of pathogens has risen markedly . This S3 guideline contains recommendations based on current evidence for the rational use of anti - microbial agents and for the prevention of inappropriate use of certain classes of antibiotics and thus of the result ing drug resistance . The prevention of recurrent urinary tract infection is considered in this guideline for the first time . METHODS The guideline was up date d under the aegis of the German Urological Society ( Deutsche Gesellschaft für Urologie ) . A systematic literature search ( period : 2008 - 2015 ) concerning the diagnosis , treatment , and prevention of uncomplicated urinary tract infections was carried out in the Cochrane Library , MEDLINE , and Embase data bases . R and omized , controlled trials and systemic review s were included . Relevant guidelines were identified in a guideline synopsis . RESULTS Symptom-oriented diagnostic evaluation is highly valued . For the treatment of cystitis , fosfomycin-trometamol , nitrofurantoin , nitroxolin , pivmecillinam and trimethoprim are all equally recommended . Fluorquinolones and cephalosporins are not recommended . Uncomplicated pyelonephritis with a mild to moderate clinical course ought to be treated with oral cefpodoxime , ceftibuten , ciprofloxacin , or levofloxacin . For acute , uncomplicated cystitis , with mild to moderate symptoms , symptomatic treatment alone may be considered instead of antibiotics after discussion of the options with the patient . Mainly non-antibiotic measures are recommended for prophylaxis against recurrent urinary tract infection . CONCLUSION Physicians who treat uncomplicated urinary tract infections should familiarize themselves with the newly revised guideline 's recommendations on the selection and dosage of antibiotic treatment so that they can responsibly evaluate and plan antibiotic treatment for their affected patients Objective To assess the impact of different management strategies in urinary tract infections . Design R and omised controlled trial . Setting Primary care . Participants 309 non-pregnant women aged 18 - 70 presenting with suspected urinary tract infection . Intervention Patients were r and omised to five management approaches : empirical antibiotics ; empirical delayed ( by 48 hours ) antibiotics ; or targeted antibiotics based on a symptom score ( two or more of urine cloudiness , urine smell , nocturia , or dysuria ) , a dipstick result ( nitrite or both leucocytes and blood ) , or a positive result on midstream urine analysis . Self help advice was controlled in each group . Main outcome measures Symptom severity ( days 2 to 4 ) and duration , and use of antibiotics . Results Patients had 3.5 days of moderately bad symptoms if they took antibiotics immediately . There were no significant differences in duration or severity of symptoms ( mean frequency of symptoms on a 0 to 6 scale : immediate antibiotics 2.15 , midstream urine 2.08 , dipstick 1.74 , symptom score 1.77 , delayed antibiotics 2.11 ; likelihood ratio test for the five groups P=0.177 ) . There were differences in antibiotic use ( immediate antibiotics 97 % , midstream urine 81 % , dipstick 80 % , symptom score 90 % , delayed antibiotics 77 % ; P=0.011 ) and in sending midstream urine sample s ( immediate antibiotics 23 % , midstream urine 89 % , dipstick 36 % , symptom score 33 % , delayed antibiotics 15 % ; P<0.001 ) . Patients who waited at least 48 hours to start taking antibiotics reconsulted less ( hazard ratio 0.57 ( 95 % confidence interval 0.36 to 0.89 ) , P=0.014 ) but on average had symptoms for 37 % longer than those taking immediate antibiotics ( incident rate ratio 1.37 ( 1.11 to 1.68 ) , P=0.003 ) , particularly the midstream urine group ( 73 % longer , 22 % to 140 % ; none of the other groups had more than 22 % longer duration ) . Conclusion All management strategies achieve similar symptom control . There is no advantage in routinely sending midstream urine sample s for testing , and antibiotics targeted with dipstick tests with a delayed prescription as backup , or empirical delayed prescription , can help to reduce antibiotic use . Study registration National Research Register N0484094184 IS RCT N : 03525333 Background : Overuse of antimicrobial therapy in the community adds to the global spread of antimicrobial resistance , which is jeopardizing the treatment of common infections . Methods : We design ed a cluster r and omized complex intervention to improve antimicrobial prescribing for urinary tract infection in Irish general practice . During a 3-month baseline period , all practice s received a workshop to promote consultation coding for urinary tract infections . Practice s in intervention arms A and B received a second workshop with information on antimicrobial prescribing guidelines and a practice audit report ( baseline data ) . Practice s in intervention arm B received additional evidence on delayed prescribing of antimicrobials for suspected urinary tract infection . A reminder integrated into the patient management software suggested first-line treatment and , for practice s in arm B , delayed prescribing . Over the 6-month intervention , practice s in arms A and B received monthly audit reports of antimicrobial prescribing . Results : The proportion of antimicrobial prescribing according to guidelines for urinary tract infection increased in arms A and B relative to control ( adjusted overall odds ratio [ OR ] 2.3 , 95 % confidence interval [ CI ] 1.7 to 3.2 ; arm A adjusted OR 2.7 , 95 % CI 1.8 to 4.1 ; arm B adjusted OR 2.0 , 95 % CI 1.3 to 3.0 ) . An unintended increase in antimicrobial prescribing was observed in the intervention arms relative to control ( arm A adjusted OR 2.2 , 95 % CI 1.2 to 4.0 ; arm B adjusted OR 1.4 , 95 % CI 0.9 to 2.1 ) . Improvements in guideline -based prescribing were sustained at 5 months after the intervention . Interpretation : A complex intervention , including audit reports and reminders , improved the quality of prescribing for urinary tract infection in Irish general practice . Trial registration : Clinical Trials.gov , no. Background and purpose : Antibiotic therapy has been the mainstay of treatment in the management of hospitalized patients with nosocomial urinary tract infection ( UTI ) ; however , its use is associated with an increase in resistance and high cost . Ibuprofen showed effectiveness in relieving symptoms of UTI , but its superiority is question able . The goal of this study was to compare the effectiveness of antibiotics against ibuprofen in relieving symptoms of UTI and to identify factors that affect symptom relief . Methods : This study was conducted in three public hospitals in Jordan . Patients with nosocomial UTI were assigned to either antibiotics or ibuprofen . Symptoms of UTI were assessed at the time of initiation of treatment and 5 days later . Conclusions : Antibiotics were more effective in relieving symptoms of UTI than Ibuprofen . Comorbidity and length of hospitalization affected symptom relief during the treatment of UTI . Implication for practice : Nurse practitioners in the clinical setting s can take an active role in helping patients with UTI to achieve relief of symptoms by supporting the use of antibiotics over ibuprofen in symptom resolution OBJECTIVES The aim was to investigate if offering symptomatic therapy ( Uva-ursi or ibuprofen ) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection ( UTI ) . METHODS A 2 × 2 factorial placebo controlled r and omized trial in primary care . The participants were 382 women aged 18 - 70 years with symptoms of dysuria , urgency , or frequency of urination and suspected by a clinician to have a lower UTI . The interventions were Uva-ursi extract and /or ibuprofen advice . All women were provided with a delayed or ' back-up ' prescription for antibiotics . Missing data were imputed using multiple imputation methods ( IS RCT N registry : IS RCT N43397016 ) . RESULTS An ITT analysis of mean score for frequency symptoms assessed on Days 2 - 4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 ( 95 % CI -0.33 to 0.21 ; p 0.661 ) , nor ibuprofen vs. no ibuprofen advice -0.01 ( 95 % CI -0.27 to 0.26 ; p 0.951 ) . There was no evidence of a reduction in antibiotic consumption with Uva-ursi ( 39.9 % vs. placebo 47.4 % ; logistic regression odds ratio ( OR ) 0.59 ( 95 % CI 0.22 - 1.58 ; p 0.293 ) but there was a significant reduction for ibuprofen advice ( 34.9 % vs. no advice 51.0 % ; OR 0.27 ( 95 % CI 0.10 to 0.72 ; p 0.009 ) . There were no safety concerns and no episodes of upper tract infection were recorded . CONCLUSIONS We found no evidence of an effect of either intervention on the severity of frequency symptoms . There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications . For every seven women given this advice , one less will use antibiotics |
10,396 | 24,924,295 | CHWs showed high adherence to test results , but in some studies a substantial group of RDT negatives received treatment .
High risk of bias was found for morbidity and mortality studies , therefore , effects on morbidity and mortality could not be estimated .
Uptake and acceptance by the community was high , however negative-tested patients did not always follow up referral advice .
RDT-based CCMm was found to be cost effective for the correct treatment of malaria in areas with low to medium malaria prevalence , but study design s were not optimal .
Discussion Trained CHWs can deliver high quality care for malaria using RDTs .
However , lower RDT specificity could lead to missed diagnoses of non-malarial causes of fever .
Integrated CCM may solve some of these issues . | Background Malaria still causes high morbidity and mortality around the world , mainly in sub-Saharan Africa .
Community case management of malaria ( CCMm ) by community health workers ( CHWs ) is one of the strategies to combat the disease by increasing access to malaria treatment .
Currently , the World Health Organization recommends to treat only confirmed malaria cases , rather than to give presumptive treatment .
Objectives This systematic review aims to provide a comprehensive overview of the success or failure of critical steps in CCMm with rapid diagnostic tests ( RDTs ) . | In a cluster r and omized trial , Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective Background In tropical Africa , where malaria is highly endemic , low grade infections are asymptomatic and the diagnosis of clinical malaria is usually based on parasite density . Here we investigate how changes in malaria control and endemicity modify diagnostic criteria of Plasmodium falciparum attacks . Methods and Findings Parasitological and clinical data from the population of Dielmo , Senegal , monitored during 20 years , are analyzed in a r and om-effect logistic regression model to investigate the relationship between the level of parasitemia and risk of fever . Between 1990 and 2010 , P. falciparum prevalence in asymptomatic persons declined from 85 % to 1 % in children 0–3 years and from 34 % to 2 % in adults ≥50 years . Thresholds levels of parasitemia for attributing fever episodes to malaria decreased by steps in relation to control policies . Using baseline threshold during following periods underestimated P. falciparum attacks by 9.8–20.2 % in children and 18.9–40.2 % in adults . Considering all fever episodes associated with malaria parasites as clinical attacks overestimated P. falciparum attacks by 42.2–68.5 % in children and 45.9–211.7 % in adults . Conclusions Malaria control modifies in all age-groups the threshold levels of parasitemia to be used for the assessment of malaria morbidity and to guide therapeutic decisions . Even under declining levels of malaria endemicity , the parasite density method must remain the reference method for distinguishing malaria from other causes of fever and assessing trends in the burden of malaria Objective In 2010 , the World Health Organization ( WHO ) published up date d guidelines emphasizing and exp and ing recommendations for a parasitological confirmation of malaria before treating with antimalarials . This study aim ed to assess differences in historic ( 2007–2008 ) ( cohort 1 ) and recent ( 2011–2012 ) ( cohort 2 ) hospital cohorts in the diagnosis and treatment of febrile illness in a low malaria prevalence area of northern Tanzania . Material s and Methods We analyzed data from two prospect i ve cohort studies that enrolled febrile adolescents and adults aged ≥13 years . All patients received quality -controlled aerobic blood cultures and malaria smears . We compared patients ' discharge diagnoses , treatments , and outcomes to assess changes in the treatment of malaria and bacterial infections . Results In total , 595 febrile in patients were enrolled from two referral hospitals in Moshi , Tanzania . Laboratory-confirmed malaria was detected in 13 ( 3.2 % ) of 402 patients in cohort 1 and 1 ( 0.5 % ) of 193 patients in cohort 2 ( p = 0.041 ) . Antimalarials were prescribed to 201 ( 51.7 % ) of 389 smear-negative patients in cohort 1 and 97 ( 50.5 % ) of 192 smear-negative patients in cohort 2 ( p = 0.794 ) . Bacteremia was diagnosed from st and ard blood culture in 58 ( 14.5 % ) of 401 patients in cohort 1 compared to 18 ( 9.5 % ) of 190 patients in cohort 2 ( p = 0.091 ) . In cohort 1 , 40 ( 69.0 % ) of 58 patients with a positive blood culture received antibacterials compared to 16 ( 88.9 % ) of 18 patients in cohort 2 ( p = 0.094 ) . In cohort 1 , 43 ( 10.8 % ) of the 399 patients with known outcomes died during hospitalization compared with 12 ( 6.2 % ) deaths among 193 patients in cohort 2 ( p = 0.073 ) . Discussion In a setting of low malaria transmission , a high proportion of smear-negative patients were diagnosed with malaria and treated with antimalarials despite up date d WHO guidelines on malaria treatment . Improved laboratory diagnostics for non-malaria febrile illness might help to curb this practice Background Early diagnosis and prompt , effective treatment of uncomplicated malaria is critical to prevent severe disease , death and malaria transmission . We assessed the impact of rapid malaria diagnostic tests ( RDTs ) by community health workers ( CHWs ) on provision of artemisinin-based combination therapy ( ACT ) and health outcome in fever patients . Methodology /Principal Findings Twenty-two CHWs from five villages in Kibaha District , a high-malaria transmission area in Coast Region , Tanzania , were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis ( CD ) only . Each CHW was r and omly assigned to use either RDT or CD the first week and thereafter alternating weekly . Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7 . The CHWs enrolled 2930 fever patients during five months of whom 1988 ( 67.8 % ) presented within 24 hours of fever onset . ACT was provided to 775 of 1457 ( 53.2 % ) patients during RDT weeks and to 1422 of 1473 ( 96.5 % ) patients during CD weeks ( Odds Ratio ( OR ) 0.039 , 95 % CI 0.029–0.053 ) . The CHWs adhered to the RDT results in 1411 of 1457 ( 96.8 % , 95 % CI 95.8–97.6 ) patients . More patients were referred on inclusion day during RDT weeks ( 10.0 % ) compared to CD weeks ( 1.6 % ) . Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis . However , no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT , supporting the safety of withholding ACT to RDT negative patients . Conclusions / Significance RDTs in the h and s of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa . Trial registration Clinical Trials.gov Objectives Parasitological confirmation of malaria prior to treatment is recommended for patients of all ages , with malaria rapid diagnostic tests ( mRDTs ) an important tool to target artemisinin-based combination therapies ( ACTs ) to patients with malaria . To evaluate the impact on case management practice s of routine government implementation of mRDTs , we conducted large-scale health facility surveys in three regions of Tanzania before and after mRDT roll-out . Methods Febrile patients at r and omly selected health facilities were interviewed about care received at the facility , and blood sample s were collected for reference blood smears . Health facility staff were interviewed about their qualifications and availability of malaria diagnostics and drugs . Results The percentage of febrile patients tested for malaria at the facility increased from 15.8 % in 2010 to 54.9 % in 2012 . ACTs were obtained by 65.8 % of patients positive by reference blood smear in 2010 and by 50.2 % in 2012 ( P = 0.0675 ) ; no antimalarial was obtained by 57.8 % of malaria-negative patients in 2010 and by 82.3 % in 2012 ( P < 0.0001 ) . Overall , ACT use decreased ( 39.9–21.3 % , P < 0.0001 ) and antibiotic use increased ( 31.2–48.5 % , P < 0.0001 ) . Conclusion Roll-out of mRDTs in Tanzania dramatically improved diagnostic testing for malaria and reduced overuse of ACTs for patients without parasitemia . However , post – roll-out almost 50 % of febrile patients did not receive a diagnostic test , and almost 50 % of patients testing positive did not receive ACTs . Stock-outs of ACTs and mRDTs were important problems . Further investigation is needed to determine reasons for not providing ACTs to patients with malaria and potential for inappropriate antibiotic use Background Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment . The aim was to assess the effect of implementing malaria rapid diagnostic tests ( m RDTs ) on prescription of anti-malarials in urban Tanzania . Methods The design was a prospect i ve collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in r and omly selected health facilities ( HF ) in Dar es Salaam , Tanzania . The participants were all clinicians and their patients in the above health facilities . The intervention consisted of training and introduction of m RDTs in all three hospitals and in six HF . Three HF without m RDTs were selected as matched controls . The use of routine m RDT and treatment upon result was advised for all patients complaining of fever , including children under five years of age . The main outcome measures were : ( 1 ) anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention ; ( 2 ) anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after m RDT implementation . Results Based on routine statistics , the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68 % ( 95%CI 57 - 80 ) in intervention and 32 % ( 9 - 54 ) in control HF . For quinine vials , the reduction was 63 % ( 54 - 72 ) in intervention and an increase of 2.49 times ( 1.62 - 3.35 ) in control HF . Before- and -after cross-sectional surveys showed a similar decrease from 75 % to 20 % in the proportion of patients receiving anti-malarial treatment ( Risk ratio 0.23 , 95%CI 0.20 - 0.26 ) . The cluster r and omized analysis showed a considerable difference of anti-malarial prescription between intervention HF ( 22 % ) and control HF ( 60 % ) ( Risk ratio 0.30 , 95%CI 0.14 - 0.70 ) . Adherence to test result was excellent since only 7 % of negative patients received an anti-malarial . However , antibiotic prescription increased from 49 % before to 72 % after intervention ( Risk ratio 1.47 , 95%CI 1.37 - 1.59 ) . Conclusions Programmatic implementation of m RDTs in a moderately endemic area reduced drastically over-treatment with anti-malarials . Properly trained clinicians with adequate support complied with the recommendation of not treating patients with negative results . Implementation of m RDT should be integrated h and -in-h and with training on the management of other causes of fever to prevent irrational use of antibiotics Background Early diagnosis , as well as prompt and effective treatment of uncomplicated malaria , are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria , reduce mortality and limit malaria transmission . The purpose of this study was to assess the performance of the malaria rapid diagnostic tests ( RDTs ) used by community health workers ( CHWs ) by comparing RDT results with two reference methods ( microscopy and Polymerase Chain Reaction , PCR ) . Methods Eight CHWs in two districts , each with a different level of endemic malaria transmission , were trained to use RDTs in the management of febrile children under five years of age . RDTs were performed by CHWs in all febrile children who consulted for fever . In parallel , retrospective parasitological diagnoses were made by microscopy and PCR . The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs . The stability of the RDTs stored by CHWs was also evaluated . Results Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010 , 89.5 % were found to be positive for malaria parasites by PCR , 51.6 % were positive by microscopy and 55.8 % were positive by RDT . The performance accuracy of the RDTs used by CHWs in terms of sensitivity , specificity , positive and negative predictive values was greater than 85 % . Concordance between microscopy and RDT , estimated by the Kappa value was 0.83 ( 95 % CI : 0.75 - 0.91 ) . RDTs stored by CHWs for 24 months were capable of detecting Plasmodium falciparum in blood at a level of 200 parasites/μl . Conclusion Introduction of easy-to-use diagnostic tools , such as RDTs , at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs Background Accurate and practical malaria diagnostics , such as immunochromatographic rapid diagnostic tests ( RDTs ) , have the potential to avert unnecessary treatments and save lives . Volunteer community health workers ( CHWs ) represent a potentially valuable human re source for exp and ing this technology to where it is most needed , remote rural communities in sub-Saharan Africa with limited health facilities and personnel . This study reports on a training programme for CHWs to incorporate RDTs into their management strategy for febrile children in the Democratic Republic of Congo , a tropical African setting ravaged by human conflict . Methods Prospect i ve cohort study , satisfaction question naire and decision analysis . Results Twelve CHWs were trained to safely and accurately perform and interpret RDTs , then successfully implemented rapid diagnostic testing in their remote community in a cohort of 357 febrile children . CHWs were uniformly positive in evaluating RDTs for their utility and ease of use . However , high malaria prevalence in this cohort ( 93 % by RDTs , 88 % by light microscopy ) limited the cost-effectiveness of RDTs compared to presumptive treatment of all febrile children , as evidence d by findings from a simplified decision analysis . Conclusions CHWs can safely and effectively use RDTs in their management of febrile children ; however , cost-effectiveness of RDTs is limited in zones of high malaria prevalence Abstract Objectives : To assess the quality and safety of having community health workers ( CHWs ) in rural Zambia use rapid diagnostic tests ( RDTs ) and provide integrated management of malaria and pneumonia . Design / methods : In the context of a cluster-r and omized controlled trial of two models for community-based management of malaria and /or non-severe pneumonia in children under 5 years old , CHWs in the intervention arm were trained to use RDTs , follow a simple algorithm for classification and treat malaria with artemether – lumefantrine ( AL ) and pneumonia with amoxicillin . CHW records were review ed to assess the ability of the CHWs to appropriately classify and treat malaria and pneumonia , and account for supplies . Patients were also followed up to assess treatment safety . Results : During the 12-month study , the CHWs evaluated 1017 children with fever and /or fast/difficult breathing and performed 975 RDTs . Malaria and /or pneumonia were appropriately classified 94–100 % of the time . Treatment based on disease classification was correct in 94–100 % of episodes . Supply management was excellent with over 98 % of RDTs , amoxicillin , and AL properly accounted for . The use of RDTs , amoxicillin , and AL was associated with few minor adverse events . Most febrile children ( 90 % ) with negative RDT results recovered after being treated with an antipyretic alone . Conclusions : Volunteer CHWs in rural Zambia are capable of providing integrated management of malaria and pneumonia to children safely and at high quality Background In Malawi essential drugs are provided free of charge to patients at all public health facilities in order to ensure equitable access to health care . The country thereby spends about 30 % of the national health budget on drugs . In order to investigate the level of drug shortages and eventually find the reasons for the drugs shortages in Malawi , we studied the management of the drug supplies for common and life threatening diseases such as pneumonia and malaria in a r and om selection of health centres . Methods In July and August 2005 we visited eight out of a total of 37 health centres chosen at r and om in the Lilongwe District , Malawi . We recorded the logistics of eight essential and widely used drugs which according to the treatment guidelines should be available at all health centres . Five drugs are used regularly to treat pneumonia and three others to treat acute malaria . Out-of-stock situations in the course of one year were recorded retrospectively . We compared the quantity of each drug recorded on the Stock Cards with the actual stock of the drug on the shelves at the time of audit . We review ed 8,968 Patient Records containing information on type and amount of drugs prescribed during one month . Results On average , drugs for treating pneumonia were out of stock for six months during one year of observation ( median value 167 days ) ; anti-malarial drugs were lacking for periods ranging from 42 to138 days . The cross-sectional audit was even more negative , but here too the situation was more positive for anti-malarial drugs . The main reason for the shortage of drugs was insufficient deliveries from the Regional Medical Store . Benzyl penicillin was in shortest supply ( 4 % received ) . The median value for non-availability was 240 days in the course of a year . The supply was better for anti-malarial drugs , except for quinine injections ( 9 % ) . Only 66 % of Stock Card records of quantities received were reflected in Patient Records showing quantities dispensed . Conclusion We conclude that for the eight index drugs the levels of supply are unacceptable . The main reason for the observed shortage of drugs at the health centres was insufficient deliveries from the Regional Medical Store . A difference between the information recorded on the Stock Cards at the health centres and that recorded in the Patient Records may have contributed to the overall poor drug supply situation . In order to ensure equitable access to life saving drugs , logistics in general should be put in order before specific disease management programmes are initiated Background Access to prompt and effective treatment is a cornerstone of the current malaria control strategy . Delays in starting appropriate treatment is a major contributor to malaria mortality . WHO recommends home management of malaria using artemisininbased combination therapy ( ACT ) and Rapid Diagnostic tests ( RDTs ) as one of the strategies for improving access to prompt and efective malaria case management . Methods A prospect i ve evaluation of the effectiveness of using community health workers ( CHWs ) as delivery points for ACT and RDTs in the home management of malaria in two districts in Zambia . Results CHWs were able to manage malaria fevers by correctly interpreting RDT results and appropriately prescribing antimalarials . All severe malaria cases and febrile non-malaria fevers were referred to a health facility for further management . There were variations in malaria prevalence between the two districts and among the villages in each district . 100 % and 99.4 % of the patients with a negative RDT result were not prescribed an antimalarial in the two districts respectively . No cases progressed to severe malaria and no deaths were recorded during the study period . Community perceptions were positive . Conclusion CHWs are effective delivery points for prompt and effective malaria case management at community level . Adherence to test results is the best ever reported in Zambia . Further areas of implementation research are discussed Shortly after Kenya introduced artemether-lumefantrine ( AL ) for first-line treatment of uncomplicated malaria , we conducted a pre-post cluster r and omized controlled trial to assess the effect of providing malaria rapid diagnostic tests ( RDTs ) on recommended treatment ( patients with malaria prescribed AL ) and overtreatment ( patients without malaria prescribed AL ) in out patients > /= 5 years old . Sixty health facilities were r and omized to receive either RDTs plus training , guidelines , and supervision ( TGS ) or TGS alone . Of 1,540 patients included in the analysis , 7 % had uncomplicated malaria . The provision of RDTs coupled with TGS emphasizing AL use only after laboratory confirmation of malaria reduced recommended treatment by 63%-points ( P = 0.04 ) , because diagnostic test use did not change ( -2%-points ) , but health workers significantly reduced presumptive treatment with AL for patients with a clinical diagnosis of malaria who did not undergo testing ( -36%-points ; P = 0.03 ) . Health workers generally adhered to RDT results when prescribing AL : 88 % of RDT-positive and 9 % of RDT-negative patients were treated with AL , respectively . Overtreatment was low in both arms and was not significantly reduced by the provision of RDTs ( -12%-points , P = 0.30 ) . RDTs could potentially improve malaria case management , but we urgently need to develop more effective strategies for implementing guidelines before large scale implementation |
10,397 | 24,289,230 | Conclusions Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients .
Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies .
These results support the conduct of adequately powered RCTs to define better the utility of continuous/extended infusions in the era of antibiotic resistance | Introduction The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials , such as extended/continuous infusions , in critically ill patients is associated with improved outcomes as compared with traditional dosing methods . | 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 OBJECTIVES To compare the plasma and subcutaneous tissue concentration-time profiles of meropenem administered by intermittent bolus dosing or continuous infusion to critically ill patients with sepsis and without renal dysfunction , and to use population pharmacokinetic modelling and Monte Carlo simulations to assess the cumulative fraction of response ( CFR ) against Gram-negative pathogens likely to be encountered in critical care units . PATIENTS AND METHODS We r and omized 10 patients with sepsis to receive meropenem by intermittent bolus administration ( n = 5 ; 1 g 8 hourly ) or an equal dose administered by continuous infusion ( n = 5 ) . Serial subcutaneous tissue concentrations were determined using microdialysis and compared with plasma data for first-dose and steady-state pharmacokinetics . Population pharmacokinetic modelling of plasma data and Monte Carlo simulations were then undertaken with NONMEM . RESULTS It was found that continuous infusion maintains higher median trough concentrations , in both plasma ( intermittent bolus 0 versus infusion 7 mg/L ) and subcutaneous tissue ( 0 versus 4 mg/L ) . All simulated intermittent bolus , extended and continuous infusion dosing achieved 100 % of pharmacodynamic targets against most Gram-negative pathogens . Superior obtainment of pharmacodynamic targets was achieved using administration by extended or continuous infusion against less susceptible Pseudomonas aeruginosa and Acinetobacter species . CONCLUSIONS This is the first study to compare the relative concentration-time data of bolus and continuous administration of meropenem at the subcutaneous tissue and plasma levels . We found that the administration of meropenem by continuous infusion maintains higher concentrations in subcutaneous tissue and plasma than by intermittent bolus dosing . Administration by extended or continuous infusion will achieve superior CFR against less-susceptible organisms in patients without renal dysfunction 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 Introduction Cefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis . Hypotheses for this failure include possible hidden side-effects ( for example , neurological ) or inappropriate pharmacokinetic/pharmacodynamic ( PK/PD ) parameters for bacteria with cefepime minimal inhibitory concentrations ( MIC ) at the highest limits of susceptibility ( 8 mg/l ) or intermediate-resistance ( 16 mg/l ) for pathogens such as Enterobacteriaceae , Pseudomonas aeruginosa and Staphylococcus aureus . We examined these issues in a prospect i ve non-interventional study of 21 consecutive intensive care unit ( ICU ) adult patients treated with cefepime for nosocomial pneumonia . Methods Patients ( median age 55.1 years , range 21.8 to 81.2 ) received intravenous cefepime at 2 g every 12 hours for creatinine clearance ( CLCr ) ≥ 50 ml/min , and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute . Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography . PK/PD parameters were computed by st and ard non-compartmental analysis . Results Seventeen first-doses and 11 steady states ( that is , four to six days after the first dose ) were measured . Plasma levels varied greatly between individuals , from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations . Nineteen out of 21 ( 90 % ) patients had PK/PD parameters comparable to literature values . Twenty-one of 21 ( 100 % ) patients had appropriate duration of cefepime concentrations above the MIC ( T > MIC ≥ 50 % ) for the pathogens recovered in this study ( MIC ≤ 4 mg/l ) , but only 45 to 65 % of them had appropriate coverage for potential pathogens with cefepime MIC ≥ 8 mg/l . Moreover , 2/21 ( 10 % ) patients with renal impairment ( CLCr < 30 ml/minute ) demonstrated accumulation of cefepime in the plasma ( trough concentrations of 20 to 30 mg/l ) in spite of dosage adjustment . Both had symptoms compatible with non-convulsive epilepsy ( confusion and muscle jerks ) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest . Conclusions These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters ( for pathogens with upper-limit MICs ) in a population of ICU adult patients . Moreover , it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr ≥ 50 ml/minute infected by pathogens with cefepime MICs ≤ 4 mg/l . On the other h and , prompt monitoring of cefepime plasma levels should be considered in case of lower CLCr or greater MICs ABSTRACT The pharmacokinetics of imipenem were studied in adult intensive care unit ( ICU ) patients during continuous venovenous hemofiltration ( CVVH ; n = 6 patients ) or hemodiafiltration ( CVVHDF ; n = 6 patients ) . Patients ( mean ± st and ard deviation age , 50.9 ± 15.9 years ; weight , 98.5 ± 15.9 kg ) received imipenem at 0.5 g every 8 to 12 h ( total daily doses of 1 to 1.5 g/day ) by intravenous infusion over 30 min . Pre- and postmembrane blood ( plasma ) and corresponding ultrafiltrate or dialysate sample s were collected 1 , 2 , 4 , and 8 or 12 h ( depending on dosing interval ) after completion of the drug infusion . Drug concentrations were measured using vali date d high-performance liquid chromatography methods . Mean systemic clearance ( CLS ) and elimination half-life ( t1/2 ) of imipenem were 145 ± 18 ml/min and 2.7 ± 1.3 h during CVVH versus 178 ± 18 ml/min and 2.6 ± 1.6 h during CVVHDF , respectively . Imipenem clearance was substantially increased during both CVVH and CVVHDF , with membrane clearance representing 25 % and 32 % of CLS , respectively . The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported . Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens ( MIC up to 2 μg/ml ) during CVVH or CVVHDF , but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs ( MIC = 4 to 8 μg/ml ) . Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients 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 Ceftazidime demonstrates time-dependent killing , which is maximal at 4 x or 5 x MIC for the organism , consequently continuous infusion ( CI ) has been proposed to ensure adequate ceftazidime concentrations for the entire course of therapy . Severe intra-abdominal infections ( IAIs ) require surgical or percutaneous drainage for management , and ceftazidime is frequently prescribed . Cardiovascular or metabolic changes and renal or liver dysfunction may alter drug pharmacokinetics during severe IAIs , and no data exist on concentrations of ceftazidime reached in the peritoneal fluid . The objectives here were to determine the pharmacokinetics of ceftazidime during continuous and intermittent administration in patients with severe IAIs , and to measure the concentrations of ceftazidime in the peritoneal exu date . Eighteen surgical patients with severe IAI and a creatinine clearance of > 30 mL/min were studied . A non-r and omized pilot study of six patients treated with CI alone was followed by a prospect i ve , r and omized comparative study of 12 patients . Pilot study patients received ceftazidime 1 g iv followed by a 4.5 g CI over 24 h. R and omized patients received either ceftazidime continuously as above or 1.5 g tds . Sample s for pharmacokinetic analyses were collected on days 2 and 4 . Ceftazidime concentrations were determined by high-performance liquid chromatography . CI result ed in a mean serum concentration > 40 mg/L and a T > 4 x MIC for most pathogens encountered in severe IAIs for > 90 % of the course of therapy in both serum and peritoneal exu date . Eight-hourly administration result ed in T > 4 x MIC for most pathogens encountered in severe IAIs for > 90 % of the dosing interval , but in peritoneal exu date for only 44 % of the dosing interval . During CI , AUCs in the peritoneal exu date were c. 60 % of the concomitant serum AUCs . In critically ill surgical patients with severe IAIs , CI of ceftazidime result ed in more favourable concentrations in serum and peritoneal exu date than 8-hourly bolus infusion 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 BACKGROUND AND OBJECTIVES The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections . Intact kidneys eliminate approximately 71 % of ampicillin and 78 % of sulbactam . Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t(1/2 ) of 2.3 hours on and 17.4 hours off dialysis . Despite its frequent use in intensive care units , there are no available dosing recommendations for patients with AKI undergoing renal replacement therapy . The aims of this study were to evaluate the pharmacokinetics of ampicillin/sulbactam in critically ill patients with AKI undergoing extended dialysis ( ED ) and to establish a dosing recommendation for this treatment method . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Twelve critically ill patients with anuric AKI being treated with ED were enrolled in a prospect i ve , open-label , observational pharmacokinetic study . Pharmacokinetics after a single dose of ampicillin/sulbactam ( 2 g/1 g ) was obtained in 12 patients . Multiple-dose pharmacokinetics after 4 days of twice-daily ampicillin/sulbactam ( 2 g/1 g ) was obtained in three patients . RESULTS The mean dialyzer clearance for ampicillin/sulbactam was 80.1 ± 7.7/83.3 ± 12.1 ml/min . The t(1/2 ) of ampicillin and sulbactam in patients with AKI undergoing ED were 2.8 ± 0.8 hours and 3.5 ± 1.5 hours , respectively . There was no significant accumulation using a twice-daily dosage of 2 g/1 g ampicillin/sulbactam . CONCLUSIONS Our data suggest that in patients treated with ED using a high-flux dialyzer ( polysulphone , 1.3 m(2 ) ; blood and dialysate flow , 160 ml/min ; treatment time , 480 minutes ) , a twice-daily dosing schedule of at least 2 g/1 g ampicillin/sulbactam , with one dose given after ED , should be used to avoid underdosing We r and omized 18 critically ill patients to receive ceftazidime 6 g/day by continuous infusion or bolus dosing ( 2 g 8 hourly ) , each with a loading dose of 12 mg/kg ceftazidime . During the first 8 h , plasma ceftazidime concentration fell below 40 mg/L in only one patient ( trough 38 mg/L ) from the infusion group , compared with eight from the bolus group ( 2 - 33 mg/L ) for periods ranging from 73 to 369 min . Thereafter all infusion patients remained above 40 mg/L for 40 h of study versus 20 - 30 % of bolus patients . The pharmacokinetic and pharmacodynamic characteristics of ceftazidime suggest that continuous infusions should be clinical ly investigated in outcome studies 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 BACKGROUND Over the past decades , the relationship between the pharmacokinetic ( PK ) properties of antibiotics , MICs , and clinical effects has been increasingly well understood . Interpatient variability in the PK profile , however , has only recently been recognized as a major factor in predicting the outcome in individual patients and establishing breakpoints for clinical susceptibility . Most predictions to date have used data from healthy volunteers . OBJECTIVE The purpose of this study was to perform Monte Carlo simulations of the PK/pharmacodynamic relationships of ceftazidime to assess whether the probability of target attainment ( PTA ) differed significantly between 3 distinct population s. To that end , population PK models of ceftazidime were developed for the 3 population s. METHODS Serum concentration-time data from earlier studies in healthy volunteers ( n = 8) , patients with cystic fibrosis ( CF ) ( n = 17 ) , and patients in the intensive care unit ( ICU ) ( n = 6 ) were used to obtain population PK parameter estimates and covariance matrices using the nonparametric adaptive grid program . The PTA for each group was obtained using 10,000 patient simulations for dosing regimens of 1000 and 2000 mg q8h over a range of MICs and percentages of time that concentrations of unbound drug remained above the MIC ( % T > MIC ) . RESULTS The relationship between the MIC and the population mean % T > MIC , as well as the PTA profiles , differed markedly between the 3 groups as a result of both differences and variations in V(d ) and Cl . Breakpoints based on a 100 % PTA for a % T > MIC of 60 % were < or = 4 , 0.5 , and 0.5 mg/L in healthy volunteers , patients with CF , and patients in the ICU , respectively . However , when PTA values between 90 % and 100 % were reevaluated and differences in clinical dosing regimens were accounted for , the result ing breakpoints were identical in the 3 groups . CONCLUSIONS PK parameter estimates for ceftazidime based on data from a small group of healthy volunteers result ed in a clinical susceptibility breakpoint comparable to those for patients with CF and patients in the ICU . Based on the study findings , this breakpoint would be < or = 4 mg/L. Patients suspected of having unusually high rates of clearance should be monitored closely 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 There is controversy over whether traditional intermittent bolus dosing or continuous infusion of beta-lactam antibiotics is preferable in critically ill patients . No significant difference between these two dosing strategies in terms of patient outcomes has been shown yet . This is despite compelling in vitro and in vivo pharmacokinetic/pharmacodynamic ( PK/PD ) data . A lack of significance in clinical outcome studies may be due to several method ological flaws potentially masking the benefits of continuous infusion observed in pre clinical studies . In this review , we explore the method ological shortcomings of the published clinical studies and describe the criteria that should be considered for performing a definitive clinical trial . We found that most trials utilized inconsistent antibiotic doses and recruited only small numbers of heterogeneous patient groups . The results of these trials suggest that continuous infusion of beta-lactam antibiotics may have variable efficacy in different patient groups . Patients who may benefit from continuous infusion are critically ill patients with a high level of illness severity . Thus , future trials should test the potential clinical advantages of continuous infusion in this patient population . To further ascertain whether benefits of continuous infusion in critically ill patients do exist , a large-scale , prospect i ve , multinational trial with a robust design is required OBJECTIVES This study aim ed to determine the steady-state serum and alveolar concentrations of linezolid administered by continuous infusion to critically ill patients with ventilator-associated pneumonia ( VAP ) . PATIENTS AND METHODS This was a prospect i ve , open-label study performed in an intensive care unit and research ward in a university hospital . Twelve critically ill adult patients with VAP received 600 mg of linezolid as a loading dose followed by 1200 mg/day by continuous infusion . After 2 days of therapy , the steady-state serum and alveolar ( collected by a mini-bronchoalveolar procedure ) concentrations of linezolid were determined by HPLC . RESULTS The median ( IQR ) serum and epithelial lining fluid ( ELF ) linezolid concentrations at steady state ( C(ss ) ) were 7.1 ( 6.1 - 9.8 ) and 6.9 ( 5.8 - 8.6 ) mg/L , respectively , and the median ( IQR ) AUC ( AUC(0 - 24 ) ) values were 169 ( 146 - 235 ) and 164 ( 139 - 202 ) mg · h/L , respectively , corresponding to a median ( IQR ) linezolid alveolar diffusion of 97 % ( 80%-108 % ) . CONCLUSIONS Our study shows that the continuous infusion of 1200 mg of linezolid daily in critically ill patients with VAP provides satisfactory pharmacokinetic results , with a linezolid alveolar diffusion of 100 % and concentrations exceeding almost twice the susceptibility breakpoint for Staphylococcus aureus ( 4 mg/L ) in both serum and ELF for 100 % of the time . However , the clinical benefit of continuous infusion in comparison with st and ard intermittent infusion is still to be determined Introduction The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia ( VAP ) due to Gram-negative bacteria . Methods This was a prospect i ve , double-blinded , r and omized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours ( April 2008 through June 2011 ) . Results The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits . The final analyses included 274 r and omized patients . The clinical cure rate at the end of therapy ( EOT ) in the microbiological intent-to-treat ( MITT ) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm ( 45.6 % versus 56.8 % ; 95 % CI , -26.3 % to 3.8 % ) . Similarly , the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP , the most common Gram-negative pathogen , in the doripenem arm compared to the imipenem-cilastatin arm ( 41.2 % versus 60.0 % ; 95 % CI , -57.2 to 19.5 ) . All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm ( 21.5 % versus 14.8 % ; 95 % CI , -5.0 to 18.5 ) and for patients with P. aeruginosa VAP ( 35.3 % versus 0.0 % ; 95 % CI , 12.6 to 58.0 ) . Conclusions Among patients with microbiologically confirmed late-onset VAP , a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin . Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome .Trial Registration Clinical Trials.gov : 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 optimal dosage of antibiotics for the treatment of patients with severe lower respiratory tract infections ( LRTI ) has not been determined but may be lower than is commonly administered at present . We have compared the efficacy of a low dosage of ceftazidime ( 1 g tds ) with the more usual dosage ( 2 g tds ) in a prospect i ve , r and omized study of the treatment of LRTI in seriously ill patients . Fifty patients on an Intensive Care Unit received one or the other regimen for 5 days ; the demographic characteristics of the two groups were comparable . There was no significant difference in terms of clinical and microbiological response rates between the two regimens . Overall , clinical resolution was documented for 86 % of patients , there was no change in 8 % and 6 % deteriorated . Microbiological eradication was achieved in 52 % of patients from whom a pathogen was isolated ( 46 % of all patients ) . We conclude that ceftazidime 1 g tds is effective treatment for severe LRTI in hospitalized patients GOAL OF THE STUDY It is well known today that the main determinant of beta-lactam antibiotics efficacy is the duration of the time that concentrations remain in excess of the minimum inhibitory concentration ( MIC ) of susceptible organism over the course of therapy . This prospect i ve study aim ed to evaluate the efficacy , in term of pharmacodynamic profile , of continuous infusion versus intermittent administration of ceftazidime in intensive care unit patients with severe nosocomial pneumonia . PATIENTS AND METHODS 16 patients under mechanical ventilation with nosocomial pneumonia were r and omised to receive either 60 mg/kg/day ceftazidime by constant rate infusion following a 20 mg/kg loading dose ( Group A ) or 20 mg/kg every 8 hour by intravenous bolus injection ( Group B ) . In both groups , serial blood sample s were collected during 48 hours ( 12 and 18 sample s in Group A and B , respectively ) after the start of drug administration . Plasma concentrations of ceftazidime were measured by high performance liquid chromatography . Based on our local bacteriological conditions , the pharmacodynamic profile of ceftazidime was assessed as the duration of time the plasma concentration remained above a desired target concentration of 20 mg/l for each regimen . RESULTS The mean time ( expressed as a percentage ) for which plasma ceftazidime concentrations were above 20 mg/l was 100 % for the continuous infusion group ( Group A ) and 56+/-33 % for the intermittent administration group ( Group B ) . CONCLUSION These findings show that ceftazidime administered by continuous infusion in critically ill patients under mechanical ventilation with nosocomial pneumonia appears to substantially improve the pharmacodynamic profile of this beta-lactam compared to the intermittent regimen ABSTRACT A continuous infusion of vancomycin ( CIV ) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal ( MRS ) infections . A multicenter , prospect i ve , r and omized study was design ed to compare CIV ( targeted plateau drug serum concentrations of 20 to 25 mg/liter ) and intermittent infusions of vancomycin ( IIV ; targeted trough drug serum concentrations of 10 to 15 mg/liter ) in 119 critically ill patients with MRS infections ( bacteremic infections , 35 % ; pneumonia , 45 % ) . Microbiological and clinical outcomes , safety , pharmacokinetics , ease of treatment adjustment , and cost were compared . Microbiological and clinical outcomes and safety were similar . CIV patients reached the targeted concentrations faster ( 36 ± 31 versus 51 ± 39 h , P = 0.029 ) and fewer sample s were required for treatment monitoring than with IIV patients ( 7.7 ± 2.2 versus 11.8 ± 3.9 per treatment , P < 0.0001 ) . The variability between patients in both the area under the serum concentration-time curve ( AUC24h ) and the daily dose given over 10 days of treatment was lower with CIV than with IIV ( variances , 14,621 versus 53,975 mg2/liter2/h2[P = 0.026 ] and 414 versus 818 g2[P = 0.057 ] , respectively ) . The 10-day treatment cost per patient was $ 454 ± 137 in the IIV group and was 23 % lower in the CIV group ( $ 321 ± 81 : P < 0.0001 ) . In summary , for comparable efficacy and tolerance , CIV may be a cost-effective alternative to IIV The objective of this study was to evaluate the relationship of the predicted pharmacodynamic parameters 24-h area under the inhibitory curve ( AUIC = area under the concentration-time curve for 24h of dosing/minimum inhibitory concentration ( AUC0 - 24/MIC ) and time above the minimum inhibitory concentration ( T > MIC ) with clinical and microbiological outcomes in patients with bacteraemia and sepsis treated with cefepime or ceftazidime . Pharmacokinetic and pharmacodynamic parameters were derived for 76 of 107 patients enrolled in two prospect i ve , r and omised , clinical trials comparing cefepime with ceftazidime for the treatment of sepsis with bacteraemia , lower respiratory tract infection or complicated urinary tract infection . The relationships between the pharmacodynamic parameters and outcomes were examined . Whilst no significant differences in clinical outcomes were observed between cefepime and ceftazidime , there were significant differences in the pharmacodynamic analysis . Patients with an AUIC > or = 250 had significantly greater clinical cure ( 79 % vs. 33 % ; P=0.002 ) and bacteriological eradication ( 96 % vs. 44 % ; P<0.001 ) than patients with an AUIC<250 . Patients with T > MIC of 100 % had significantly greater clinical cure ( 82 % vs. 33 % ; P=0.002 ) and bacteriological eradication ( 97 % vs. 44 % ; P<0.001 ) than patients with T > MIC of < 100 % . Both microbiological and clinical cure rates were suboptimal in patients receiving cefepime or ceftazidime for the treatment of serious infections if the AUIC was < 250 or T > MIC was < 100 % 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 ABSTRACT The time that concentrations in serum are above the MIC ( T > MIC ) is the pharmacokinetic/pharmacodynamic parameter correlating with the therapeutic efficacy of β-lactam antibiotics . The aim of this study was to demonstrate the T > MIC of meropenem when administered by a 3-h infusion compared with that when administered by bolus injection . The study was conducted with nine patients with ventilator-associated pneumonia . Each subject received meropenem in three regimens consecutively : ( i ) bolus injection of 1 g every 8 h for 24 h ; ( ii ) 3-h infusion of 1 g every 8 h for 24 h ; and ( iii ) 3-h infusion of 2 g every 8 h for 24 h. Following bolus injection , the percentages of the T > MICs of 16 , 8 , 4 , and 1 μg/ml were 28.33 % ± 11.67 % , 45.89 % ± 22.90 % , 57.00 % ± 24.82 % , and 74.67 % ± 17.94 % of an 8-h interval , respectively . For the 3-h infusion of 1 g of meropenem , the percentages of the T > MICs of 16 , 8 , 4 , and 1 μg/ml were 37.78 % ± 20.57 % , 58.11 % ± 24.38 % , 72.67 % ± 21.97 % , and 93.56 % ± 6.84 % of an 8-h interval , respectively . For the 3-h infusion of 2 g of meropenem , the percentages of the T > MICs of 16 , 8 , 4 , and 1 μg/ml were 57.89 % ± 24.26 % , 72.89 % ± 22.40 % , 85.56 % ± 16.42 % , and 98.56 % ± 3.28 % of an 8-h interval , respectively . In conclusion , a 3-h infusion result ed in greater T > MICs than those after a bolus injection . For the treatment of infections caused by pathogens with intermediate resistance , a 3-h infusion of 2 g of meropenem every 8 h can provide concentrations in serum above the MIC of 16 μg/ml for almost 60 % of an 8-h interval Objective : To investigate daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis to develop dosing recommendations . Design : Prospect i ve , open-label pharmacokinetic study . Setting : Intensive care units located within a teaching medical center . Patients : Eight adults with known/suspected Gram-positive infections receiving continuous venovenous hemodialysis and daptomycin . Interventions : Daptomycin at 8 mg/kg intravenously over 30 mins . Serial blood and effluent sample s were collected over the next 48 hrs . Daptomycin protein binding was determined by equilibrium dialysis . Daptomycin continuous venovenous hemodialysis transmembrane clearance was determined by dividing daptomycin effluent by serum concentrations and multiplying by mean effluent production rate for each subject . Equations describing a two-compartment , open-pharmacokinetic model were fitted to each subject 's daptomycin concentration-time data and pharmacokinetic parameters were determined by st and ard methods . Serum concentration-time profiles were simulated for two daptomycin regimens ( 8 mg/kg every 48 hrs and 4 mg/kg every 24 hrs ) . Measurements and Main results : A total of 7.7 ± 0.6 mg/kg ( mean ± sd ) of daptomycin was administered , result ing in an observed peak concentration of 81.2 ± 19.0 & mgr;g/mL. Daptomycin steady-state volume of distribution ( 0.23 ± 0.14 L/kg ) and free fraction ( 17.5 % ± 5.0 % ) were increased in critically ill subjects receiving continuous venovenous hemodialysis compared with previous values reported in healthy volunteers . Daptomycin transmembrane clearance ( 6.3 ± 2.9 mL/min ) accounted for more than half of total clearance ( 11.3 ± 4.7 mL/min ) . Simulations demonstrated 8 mg/kg daptomycin every 48 hrs would result in higher peak ( 88.8 ± 20.0 & mgr;g/mL vs. 53.0 ± 12.3 & mgr;g/mL ) and lower trough concentrations ( 7.2 ± 5.2 & mgr;g/mL vs. 12.3 ± 5.1 & mgr;g/mL ) than 4 mg/kg every 24 hrs . Conclusions : Daptomycin at 8 mg/kg every 48 hrs in critically ill patients receiving continuous venovenous hemodialysis result ed in good drug exposure , achieved high peak concentrations to maximize daptomycin 's concentration-dependent activity , and result ed in trough concentration that would minimize the risk of myopathy . Clinical Trials.gov Identifier : NCT00663403 The pharmacokinetics and pharmacodynamics of meropenem were investigated in 14 critically ill patients with sepsis . Patients with creatinine clearance ( CrCl ) higher than 50 ml/min received 1 g meropenem three times daily ( Group I ) and patients with CrCl lower than 50 ml/min received 1 g meropenem twice daily ( Group II ) . Meropenum concentrations in plasma were determined by high performance liquid chromatography with UV detection . The pharmacokinetic parameters differed between the two groups as follows , Group I , maximal concentration 56.3 + /- 19.1 microg/ml ; trough concentration 3.3 + /- 2.5 microg/ml ; elimination half life 2.5 + /- 1.2 h ; clearance ( Cl ) 155.8 + /- 40.6 ml/min ; MRT 2.2 + /- 0.4 h ; steady state volume of distribution ( V(ss ) ) 21.7 + /- 5.7 l , and AUC(-8 ) 119.4 + /- 32.6 microg/ml h. Group II , maximal concentration 71.1 + /- 5.1 microg/ml ; trough concentration 3.4 + /- 1.8 microg/ml ; elimination half life 3.9 + /- 1.6 h ; Cl 77.7 + /- 15.8 ml/min ; MRT 3.5 + /- 0.6 h ; V(ss ) , 17.1 + /- 2.1 l , and AUC(0 - 12 ) 230.2 + /- 43.3 microg/ml h. The most frequently isolated bacteria from blood and wound infections were Acinetobacter baumanii , Pseudomonas aeruginosa , Klebsiella pneumoniae and Escherichia coli ; their meropenem minimal inhibitory concentrations ( MICs ) ranged from 0.064 to 3.0 mg/l . In most cases the pharmacodynamic parameters , measured as T > MIC index , were higher than 75 % . In both groups , patients with susceptible pathogens ( MIC<1 mg/l ) had meropenem plasma levels which exceeded the MIC for the whole dosing interval . When pathogens were highly resistant ( A. baumanii or P. aeruginosa ) the T > MIC indices were lower BACKGROUND Because of the high frequency of multidrug resistant bacteria in our intensive care units ( ICUs ) , we implemented a ventilator-associated pneumonia ( VAP ) clinical pathway based on unit-specific minimum inhibitory concentration ( MIC ) distributions and pharmacodynamic modeling in 3 of our ICUs . METHODS This was a prospect i ve , observational evaluation with a historical control group in adult patients ( n = 168 ) who met clinical and radiologic criteria for VAP . Monte Carlo simulation was used to determine antibiotic regimens having the greatest likelihood of achieving bactericidal exposures against Pseudomonas aeruginosa . Antibiotic regimens were incorporated into an ICU-specific computerized clinical pathway as empiric agents of choice . RESULTS Pharmacodynamic modeling found 3-hour infusions of cefepime 2 g every 8 hours or meropenem 2 g every 8 hours plus tobramycin and vancomycin would provide the greatest probability of empirically treating VAP in these ICUs . Infection-related mortality was reduced by 69 % ( 8.5 % vs 21.6 % ; P = .029 ) , infection-related length of stay was shorter ( 11.7 + /- 8.1 vs 26.1 + /- 18.5 ; P < .001 ) , and fewer superinfections were observed in patients treated on the pathway . A number of patients with nonsusceptible P aeruginosa were successfully treated with high-dose , 3-hour infusion regimens . CONCLUSIONS In our ICUs where multidrug resistant bacteria are common , an approach considering ICU-specific antibiotic MICs coupled with pharmacodynamic dosing strategies result ed in improved outcomes and shorter duration of treatments BACKGROUND Methicillin-resistant Staphylococcus aureus ( MRSA ) is a leading cause of hospital-acquired pneumonia ( HAP ) , ventilator-associated pneumonia ( VAP ) , and health-care-associated pneumonia ( HCAP ) . These infections are associated with significant morbidity , mortality , and cost . The impact of vancomycin minimum inhibitory concentration ( MIC ) on mortality for patients with MRSA pneumonia has not been determined . METHODS Adult patients in ICUs with a diagnosis of MRSA HAP , VAP , or HCAP were entered in the study . Clinical and laboratory information were prospect ively collected . Vancomycin MIC and heteroresistance were determined for each MRSA isolate . Data were collected from February 2006 through August 2007 . The primary outcome variable was all-cause mortality at day 28 . A propensity score approach was used to adjust for confounding variables . RESULTS The study sample consisted of 158 patients . All-cause mortality at day 28 was 32.3 % . The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL ( 115/158 , 72.8 % ) . Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL ( P ≤ .001 ) . Heteroresistance to vancomycin , demonstrated in 21.5 % isolates , was not associated with mortality . CONCLUSIONS Mortality in patients with MRSA HAP , VAP , and HCAP increases as a function of the vancomycin MIC , even for strains with MIC values within the susceptible range . Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia . The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution , and alternative therapies should be considered 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 Objective : To determine the steady-state plasma and epithelial lining fluid concentrations of intravenous levofloxacin , 500 mg , administered once or twice daily in critically ill patients with severe community-acquired pneumonia . Design : Prospect i ve , open-label study . Setting : An intensive care unit and a clinical pharmacokinetic laboratory in two university hospitals . Patients : Twenty-four adult patients with severe community-acquired pneumonia and receiving mechanical ventilation were enrolled . Interventions : All subjects received 1-hr intravenous infusions of 500 mg levofloxacin once or twice daily . The plasma and epithelial lining fluid levofloxacin concentrations were determined at steady-state after 2 days of therapy with high-performance liquid chromatography . Measurements and main results : The median ( interquartile range [ IQR ] ) plasma and epithelial lining fluid peak levofloxacin concentrations were 12.6 ( IQR , 12.0–14.1 ) and 11.9 ( IQR , 8.7–13.7 ) mg/L , respectively , in the once-daily group and 19.7 ( IQR , 19.0–22.0 ) and 17.8 ( IQR , 16.2–23.5 ) mg/L in the twice-daily group , showing a pulmonary percentage penetration of > 100 % in both groups . The median ( IQR ) total body exposures were 151 ( IQR , 137–174 ) and 416 ( IQR , 406–472 ) mg·hr/L , respectively , in the once-daily and twice-daily groups . Conclusions : Our results suggest that in critically ill patients who are receiving mechanical ventilation and have severe community-acquired pneumonia and creatinine clearance of > 40 mL/min , the administration of 500 mg of intravenous levofloxacin once and twice daily allows for the exceeding of pharmacodynamic thresholds predictive of outcome ( i.e. , peak concentration to minimum inhibitory concentration ratio of > 10 or area under concentration-time curve to minimal inhibitory concentration ratio of > 125 hrs ) both in serum and epithelial lining fluid for pathogens with minimum inhibitory concentration values of ≤1 mg/L and > 1 mg/L , respectively STUDY OBJECTIVE To compare the effectiveness of extended-infusion piperacillin-tazobactam with that of similar-spectrum , nonextended-infusion [H9252]-lactam antibiotics in the treatment of gram-negative infections . DESIGN Multicenter , retrospective medical record review . SETTING Fourteen hospitals throughout the United States . PATIENTS A total of 359 adults treated for gram-negative infections between January 1 , 2007 , and February 28 , 2010 , with either 4-hour extended-infusion piperacillin-tazobactam ( 186 patients ) or nonextended-infusion comparator antibiotics ( 173 patients ) , which consisted of cefepime , ceftazidime , imipenem-cilastatin , meropenem , doripenem , or piperacillin-tazobactam . MEASUREMENTS AND MAIN RESULTS Deidentified data were collected on demographics , renal function , Acute Physiology and Chronic Health Evaluation II score , chronic health conditions , source of infection and type of organism , intensive care unit ( ICU ) length of stay , total length of stay , type and duration of antimicrobial therapy , and in-hospital mortality . The primary outcome was mortality rate of the patients receiving extended-infusion piperacillin-tazobactam versus those receiving nonextended-infusion comparator antibiotics . Secondary outcomes were hospital length of stay , ICU length of stay , and total duration of antibiotic therapy . Baseline characteristics were similar between groups , except a significantly lower proportion of patients in the extended-infusion group were treated with a concomitant intravenous aminoglycoside ( 5.9 % vs 16.2 % , p<0.01 ) , were infected with Pseudomonas species ( 22.6 % vs 39.9 % , p<0.01 ) , or had positive respiratory cultures ( 30.7 % vs 43.4 % , p=0.01 ) . Antibiotic duration , hospital length of stay , and ICU length of stay were similar between groups . In-hospital mortality was significantly decreased in the extended-infusion piperacillin-tazobactam group versus those receiving comparator antibiotics ( 9.7 % vs 17.9 % , p=0.02 ) . Multivariate analysis confirmed that extended-infusion piperacillin-tazobactam prolonged survival by 2.77 days ( p<0.01 ) and reduced the risk of mortality ( odds ratio 0.43 , p=0.05 ) . CONCLUSION Pharmacodynamic dosing using extended-infusion piperacillintazobactam demonstrated favorable outcomes , including mortality , when compared with nonextended-infusion , similar-spectrum [H9252]-lactams in the treatment of patients with documented gram-negative infections . Prospect i ve , r and omized trials are needed to further corroborate these findings Cefmenoxime concentration/effect relationships were retrospectively explored for gram-negative bacteria isolated from 14 critical care patients treated for nosocomial pneumonia . The effects of cefmenoxime concentrations on in vitro growth kinetics of 21 isolated pathogens were studied using the Abbott MS-2 Research System , from which a dynamic response concentration was derived . Serum pharmacokinetic profiles were obtained in each patient . These data were used to calculate the in vivo total area under the curve over dynamic response concentration and the time that cefmenoxime concentrations exceeded the dynamic response concentration for each bacteria . The same determinations were made in 18 patients prospect ively treated , except that dosage was optimized on the basis of previous mathematical relations to achieve bacterial eradication in four days . This method of dosage optimization is termed dual individualization . Serial cultures of infected tissues were evaluated to determine the number of days to the eradication of bacteria , and the pharmacokinetic and pharmacodynamic variables were used to describe the bacteriologic response of the original pathogen isolated in pretreatment culture . Bacterial eradication rates could be described from cefmenoxime pharmacokinetics in the patient and from the relation between concentration and bacterial inhibition . Patients who were prospect ively treated using these retrospectively derived relationships had a predictable day of bacterial eradication . This , in turn , was associated with a shorter duration of treatment ( p less than 0.05 ) . The success of prospect i ve dual individualization is encouraging and suggests that more precise optimization of antibiotic dosage can yield a predictable rate of bacterial eradication from the infection site The optimal antibiotic dosage in serious chest infections is not established and commonly used regimens may well be excessive . We have compared the efficacy of a low dose of cefotaxime ( 2 g every 12 h ) with a more usual dose ( 2 g every 8 h ) in a prospect i ve , r and omized study of the treatment of chest infections in the seriously ill . Fifty intensive care unit patients received either regimen for five days . The two groups appeared demographically comparable . Clinical resolution occurred in 86 percent , no change occurred in 4 percent , and deterioration occurred in 10 percent . Microbiologic clearance occurred in 52 percent of those in whom a pathogen was isolated ( 46 percent of patients ) . There was no significant difference in clinical or microbiologic response between the two regimens . It is concluded that cefotaxime in a dose of 2 g twice daily is effective in the treatment of serious chest infections Objectives To develop a population pharmacokinetics model for cefpirome in ICU patients , to assess pharmacokinetic-pharmacodynamic profiles vs. MIC distribution of likely ICU pathogens , and to assess their expected cumulative fraction of response ( CFR ) . Design and setting Prospect i ve observational study in a multidisciplinary ICU . Measurements and results Twelve patients received 2 g cefpirome intravenously over 12 h. Thirteen blood sample s were taken on two occasions . Demographic and creatinine clearance data were collected . Based on the final covariate model obtained using NONMEM , Monte Carlo simulations were undertaken to simulate free-drug concentrations for two administration methods : intermittent bolus administration ( IBA ) and continuous infusion ( CI ) with a loading dose of 0.5 g. Concentration-time profiles were evaluated by the probability of achieving free-drug concentrations above the MIC for more than 65 % of dosing interval . Using MIC distributions from the EUCAST programme the CFR for each method was evaluated . A three-compartment model with zero-order input best described the concentration-time data . The CFR for Escherichia coli and Klebsiella spp . was greater than 97 % in all IBA and CI doses but for Pseudomonas aeruginosa , and Acinetobacter spp . achieved target concentrations of 56 % and 46 % , respectively . High-dose CI cefpirome ( 6 g/day ) for P. aeruginosa and Acinetobacter spp . was required to achieve CFR of 89 % . Conclusion Measured creatinine clearance appears to be a good marker of cefpirome clearance and potentially could be used to individualise cefpirome therapy . When given as IBA or CI for E. coli and Klebsiella spp . , cefpirome should be successful . Cefpirome fails to achieve the bactericidal target even when administered at high-doses such as 6 g/day for P. aeruginosa and Acinetobacter spp . Prospect i ve clinical studies are needed to conclusively vali date these findings The aim of this study was to evaluate the effect of augmented renal clearance ( ARC ) on vancomycin serum concentrations in critically ill patients . This prospect i ve , single-centre , observational , cohort study included 93 consecutive , critically ill septic patients who started treatment that included vancomycin by continuous infusion , admitted over a 2-year period ( March 2006 to February 2008 ) . ARC was defined as 24-h creatinine clearance ( CL(Cr))>130 mL/min/1.73 m(2 ) . Two groups were analysed : Group A , 56 patients with a CL(Cr)≤130 mL/min/1.73 m(2 ) ; and Group B , 37 patients with a CL(Cr)>130 mL/min/1.73 m(2 ) . Vancomycin therapeutic levels were assessed on the first 3 days of treatment ( D(1 ) , D(2 ) and D(3 ) ) . Serum vancomycin levels on D(1 ) , D(2 ) and D(3 ) , respectively , were 13.1 , 16.6 and 18.6 μmol/L for Group A and 9.7 , 11.7 and 13.8 μmol/L for Group B ( P<0.05 per day ) . The correlation between CL(Cr ) and serum vancomycin on D(1 ) was -0.57 ( P<0.001 ) . ARC was strongly associated with subtherapeutic vancomycin serum concentrations on the first 3 days of treatment Objective To investigate the pharmacokinetics of levofloxacin and the pharmacokinetic-pharmacodynamic appropriateness of its total body exposure in patients in the intensive care unit ( ICU ) treated for early-onset ventilator-associated pneumonia ( VAP ) with intravenous levofloxacin 500 mg twice daily . Design Prospect i ve non-blinded pharmacokinetic-pharmacodynamic study . Participants Ten critically ill adult patients with normal renal function . Methods Blood and urine sample s were collected at appropriate times during a 12-hour administration interval at steady state . Levofloxacin concentrations were determined by high-performance liquid chromatography . Clinical and microbiological outcomes were assessed . Results Levofloxacin pharmacokinetics were only partially comparable with those obtained from literature data for healthy volunteers . Area under the concentration-time curve ( AUCτ ) over the 12-hour dosage interval was about 30–40)% lower than in healthy volunteers ( 33.90 vs 49.60 mg · h/L ) . The reduced exposure may be due to a greater clearance of levofloxacin ( 0.204 vs 0.145 L/h/kg [ 3.40 vs 2.42 mL/min/kg ] ) , leading to a shorter elimination half-life ( 5.2 vs 7.6 hours ) . Cumulative urinary excretion during the 12-hour dosage interval confirmed the greater excretion of unchanged drug in these patients compared with healthy subjects ( 76 % vs 68 % ) . Coadministered drugs used to treat underlying diseases ( dopamine , furosemide , mannitol ) may at least partially account for this enhanced elimination in critically ill patients . Intravenous levofloxacin 500 mg twice daily ensured a median Cmax/MIC ( maximum plasma concentration/minimum inhibitory concentration ) ratio of 102 and a median 24-hour AUC/MIC ratio of 930 SIT−1 · h ( inverse serum inhibitory titre integrated over time ) against methicillinsensitive Staphylococcus aureus and Haemophilus influenzile . The overall success rate of the assessable cases was 75 % ( 6/8 ) . Bacterial eradication was obtained in all of the assessable cases ( 8/8 ) , but a superinfection ( Acinetobacter anitratus , Pseudomonas aeruginosa ) occurred in three cases . Conclusions The findings support the suitability of intravenous levofloxacin 500 mg twice daily in the treatment of early-onset VAP in ICU patients with normal renal function . Levofloxacin may represent a valid alternative to non-pseudomonal β-lactams or aminoglycosides in the empirical treatment of early-onset VAP . However , further larger studies are warranted to investigate its efficacy Abstract Objective : A prospect i ve pharmacokinetic study was performed in Caucasian patients from an intensive care unit with respiratory support to evaluate the influence of this circumstance on the pharmacokinetic behaviour of levofloxacin . Patients and methods : A st and ard dosage regimen of 500 mg/day was administered to nine Caucasian patients included in the study , irrespective of their demographic characteristics . The experimental data on plasma concentrations were analysed by independent-modelling techniques to estimate the following pharmacokinetic parameters : area under the plasma concentration-time curve ( AUC ) , volume of distribution at steady state ( Vss ) , plasma clearance ( CL ) , maximum plasma concentration at steady state ( Cmax , ss ) and elimination half-life ( t½β ) . Multiple regression analysis was applied to establish the type of correlation between the pharmacokinetic parameters and patient characteristics ; the Monte Carlo simulation technique was implemented for the pharmacokinetic/pharmacodynamic analysis based on the probability distribution of the values of AUC/ minimum inhibitory concentration ( MIC ) and Cmax , ss/MIC observed in this group of patients . Results and conclusion : The results show that for AUC the simplest linear model with creatinine clearance as the only independent variable fits the data at a 99 % confidence level , explaining more than 85 % of the observed variability in this parameter . The volume of distribution , however , showed a statistical correlation with the severity of the illness ( Simplified Acute Physiology Score II ) , although total bodyweight also explains a high percentage of variability of these parameters . Since the group of patients included in the study was small and also included obese individuals , it is difficult to estimate with precision the contribution of each circumstance ( overweight or illness severity ) to the pharmacokinetic behaviour of levofloxacin To characterize the PK/PD of biapenem ( BIPM ) in critically ill patients under continuous venovenous hemodiafiltration ( CVVHDF ) , we conducted a prospect i ve , open-label study in nine adult CVVHDF patients with acute renal failure at the Critical Care Medical Center , Hiroshima Prefectural Hospital . Plasma and filtrate sample s were obtained at six time points . The concentrations of BIPM in plasma and filtrate were determined by HPLC . PK parameters were analyzed using Monte Carlo simulation with MIC data . BIPM concentrations in the plasma and CVVHDF filtrate peaked at the end of infusion , and the values were similar . The drug clearance by CVVHDF and non-CVVHDF was 1.28 + /- 0.14 and 9.05 + /- 4.05 L/h , respectively . Monte Carlo simulation showed that the more administration times , there were the higher the probability . In conclusion , a dosing regimen of 300 mg BIPM q8h had a higher probability of therapeutic efficacy than q12h in patients with severe sepsis under CVVHDF 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 : β-Lactam antibiotics demonstrate time-dependent killing . Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs , despite limited evidence suggesting improved clinical results . OBJECTIVE : To determine whether prolonged infusion of β-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection . METHODS : We conducted a single-center , before-after , comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital , an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis , MO . Outcomes were compared between patients who received st and ardized dosing of meropenem , piperacillin-tazobactam , or cefepime as an intermittent infusion over 30 minutes ( January 1 , 2010 , to June 30 , 2010 ) and patients who received prolonged infusion over 3 hours ( August 1 , 2010 , to January 31 , 2011 ) . RESULTS : A total of 503 patients ( intermittent infusion , n = 242 ; prolonged infusion , n = 261 ) treated for gram-negative infection were included in the clinical ly evaluable population . Approximately 50 % of patients in each group received cefepime and 20 % received piperacillin-tazobactam . More patients in the intermittent infusion group received meropenem ( 35.5 % vs 24.5 % ; p = 0.007 ) . Baseline characteristics were similar between groups , with the exception of a greater occurrence of chronic obstructive pulmonary disease ( COPD ) in the intermittent infusion group . Treatment success rates in the clinical ly evaluable group were 56.6 % for intermittent infusion and 51.0 % for prolonged infusion ( p = 0.204 ) , and in the microbiologically evaluable population , 55.2 % for intermittent infusion and 49.5 % for prolonged infusion ( p = 0.486 ) . Fourteen-day , 30-day , and inhospital mortality rates in the clinical ly evaluable population for the intermittent and prolonged infusion groups were 13.2 % versus 18.0 % ( p = 0.141 ) , 23.6 % versus 25.7 % ( p = 0.582 ) , and 19.4 % versus 23.0 % ( p = 0.329 ) . CONCLUSIONS : Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success , mortality , or hospital length of stay . These results were confirmed after controlling for potential confounders in a multivariate analysis 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 Ventilator-associated pneumonia ( VAP ) occurs in nearly one-third of mechanically ventilated patients in the Intensive Care Unit . Piperacillin/tazobactam ( TZP ) is currently recommended in the empirical treatment of VAP , but intermittent dosing may result in inadequate serum concentrations . The efficacy and costs of continuous infusion ( CI ) of TZP , using therapeutic drug monitoring for real-time dose adjustment , was assessed in a prospect i ve pilot study of 16 patients with VAP . TZP was given as a loading dose of 2.0/0.25 g followed by a CI of 10.0/1.25 g daily . Rapid antimicrobial susceptibility testing was used to determine the minimum inhibitory concentration ( MIC ) of the pathogens . TZP concentrations were determined by high-pressure liquid chromatography before and at 1 , 6 , 12 , 24 , 48 , 72 and 96 h after the onset of administration . Dosages were adjusted to maintain piperacillin concentrations four-fold above the MIC ( T>4 × MIC ) of the pathogen , with a maximum dose of 16.0/2.0 g. The cost of the total TZP administered was compared with the cost of a st and ard TZP regimen ( 16.0/2.0 g ) if given over the same period of time . The median MIC for TZP was 1 μg/mL ( range 0.025 - 32 μg/mL ) . TZP concentrations were adequate for 71 % of pathogens on the first day of therapy . Clinical cure was achieved in 9/10 patients who had adequate drug concentrations and in 3/6 patients with insufficient levels . The daily dose of TZP received by CI was 37.5 % less than that of a st and ard regimen , which corresponds to a saving of € 15 on daily therapy costs compared with the st and ard regimen . In conclusion , CI of TZP achieved optimal drug concentrations in most patients with VAP , with a favourable impact on costs . Adequate drug concentrations were achieved for MIC ≤ 4 μg/mL , but higher dosages should be considered for the treatment of pathogens with low susceptibility thresholds OBJECTIVE To develop and vali date a new Simplified Acute Physiology Score , the SAPS II , from a large sample of surgical and medical patients , and to provide a method to convert the score to a probability of hospital mortality . DESIGN AND SETTING The SAPS II and the probability of hospital mortality were developed and vali date d using data from consecutive admissions to 137 adult medical and /or surgical intensive care units in 12 countries . PATIENTS The 13,152 patients were r and omly divided into developmental ( 65 % ) and validation ( 35 % ) sample s. Patients younger than 18 years , burn patients , coronary care patients , and cardiac surgery patients were excluded . OUTCOME MEASURE Vital status at hospital discharge . RESULTS The SAPS II includes only 17 variables : 12 physiology variables , age , type of admission ( scheduled surgical , unscheduled surgical , or medical ) , and three underlying disease variables ( acquired immunodeficiency syndrome , metastatic cancer , and hematologic malignancy ) . Goodness-of-fit tests indicated that the model performed well in the developmental sample and vali date d well in an independent sample of patients ( P = .883 and P = .104 in the developmental and validation sample s , respectively ) . The area under the receiver operating characteristic curve was 0.88 in the developmental sample and 0.86 in the validation sample . CONCLUSION The SAPS II , based on a large international sample of patients , provides an estimate of the risk of death without having to specify a primary diagnosis . This is a starting point for future evaluation of the efficiency of intensive care units CONTEXT Evaluation of trends in organ dysfunction in critically ill patients may help predict outcome . OBJECTIVE To determine the usefulness of repeated measurement the Sequential Organ Failure Assessment ( SOFA ) score for prediction of mortality in intensive care unit ( ICU ) patients . DESIGN Prospect i ve , observational cohort study conducted from April 1 to July 31 , 1999 . SETTING A 31-bed medicosurgical ICU at a university hospital in Belgium . PATIENTS Three hundred fifty-two consecutive patients ( mean age , 59 years ) admitted to the ICU for more than 24 hours for whom the SOFA score was calculated on admission and every 48 hours until discharge . MAIN OUTCOME MEASURES Initial SOFA score ( 0 - 24 ) , Delta-SOFA scores ( differences between subsequent scores ) , and the highest and mean SOFA scores obtained during the ICU stay and their correlations with mortality . RESULTS The initial , highest , and mean SOFA scores correlated well with mortality . Initial and highest scores of more than 11 or mean scores of more than 5 corresponded to mortality of more than 80 % . The predictive value of the mean score was independent of the length of ICU stay . In univariate analysis , mean and highest SOFA scores had the strongest correlation with mortality , followed by Delta-SOFA and initial SOFA scores . The area under the receiver operating characteristic curve was largest for highest scores ( 0.90 ; SE , 0.02 ; P<.001 vs initial score ) . When analyzing trends in the SOFA score during the first 96 hours , regardless of the initial score , the mortality rate was at least 50 % when the score increased , 27 % to 35 % when it remained unchanged , and less than 27 % when it decreased . Differences in mortality were better predicted in the first 48 hours than in the subsequent 48 hours . There was no significant difference in the length of stay among these groups . Except for initial scores of more than 11 ( mortality rate > 90 % ) , a decreasing score during the first 48 hours was associated with a mortality rate of less than 6 % , while an unchanged or increasing score was associated with a mortality rate of 37 % when the initial score was 2 to 7 and 60 % when the initial score was 8 to 11 . CONCLUSIONS Sequential assessment of organ dysfunction during the first few days of ICU admission is a good indicator of prognosis . Both the mean and highest SOFA scores are particularly useful predictors of outcome . Independent of the initial score , an increase in SOFA score during the first 48 hours in the ICU predicts a mortality rate of at least 50 % Objective To compare the pharmacokinetic parameters of sequential intravenous and subcutaneous teicoplanin in the plasma of surgical intensive care unit patients . Design and setting Prospect i ve , r and omized , crossover study in the surgical ICU of a university hospital . Patients Twelve patients with a suspected nosocomial infection , a serum albumin level higher than 10 g/l , body mass index less than 28 kg/m2 , and estimated creatinine clearance higher than 70 ml/min . Interventions Teicoplanin was first administered intravenously as a loading dose of 6 mg/kg per 12 h for 48 h and then continued at a daily dose of 6 mg/kg . On the fourth day patients were r and omized in two groups according to the order of the pharmacokinetic studies . Measurements and results Serial plasma sample s were obtained to measure teicoplanin levels . Compared with a 30-min intravenous infusion the peak concentration of teicoplanin after a 30-min subcutaneous administration occurred later ( median 7 h , range 5–18 ) and was lower ( 16 µg/ml , 9–31 ; vs. 73 , 53–106 ) . Despite large and unpredictable interindividual differences no significant differences between subcutaneous and intravenous administration were observed in : trough antibiotic concentrations ( 10 µg/ml , 6–24 ; vs. 9 , 5–30 ) , the area under the teicoplanin plasma concentration vs. time curves from 0 to 24 h ( AUC0–24h ; 309 µg/ml per minute , 180–640 ; vs. 369 , 171–955 ) , the proportion of the dosing interval during which the plasma teicoplanin concentration exceeded 10 µg/ml ( 96 % , 0–100 % ; vs. 79 % , 13–100 % ) , and the ratio of AUC0–24h to 10 ( 77 , 45–160 ; vs. 92 , 43–239 ) . Conclusions In critically ill patients without vasopressors a switch to the subcutaneous teicoplanin after an initial intravenous therapy seems to give comparable pharmacodynamic indexes of therapeutic success Objectives : In critically ill patients receiving continuous renal replacement therapy , we aim ed to assess the variability of antibiotic trough concentrations , the influence of effluent flow rates on such concentrations , and the incidence of suboptimal antibiotic dosage . Design : Prospect i ve , observational , multicenter , pharmacokinetic study . Setting : Four tertiary intensive care units within the multicenter RENAL r and omized controlled trial of continuous renal replacement therapy intensity . Patients : Twenty-four critically ill adult patients with acute kidney injury receiving ciprofloxacin , meropenem , piperacillin/tazobactam , or vancomycin during continuous renal replacement therapy . Interventions : We obtained trough blood sample s and measured antibiotic concentrations . Measurements and Main Results : We obtained data from 40 dosing intervals and observed wide variability in trough concentrations ( 6.7-fold for meropenem , 3.8-fold for piperacillin , 10.5-fold for tazobactam , 1.9-fold for vancomycin , and 3.9-fold for ciprofloxacin ) . The median ( interquartile range ) trough concentrations ( mg/L ) for meropenem was 12.1 ( 7.8–18.4 ) , 105.0 (74.4–204.0)/3.8 ( 3.4–21.8 ) for piperacillin/tazobactam , 12.0 ( 9.8–16.0 ) for vancomycin , and 3.7 ( 3.0–5.6 ) for ciprofloxacin . Overall , 15 % of dosing intervals did not meet predetermined minimum therapeutic target concentrations , 40 % did not achieve the higher target concentration , and , during 10 % of dosing intervals , antibiotic concentrations were excessive . No difference , however , was found between patients on the basis of the intensity of continuous renal replacement therapy ; this effect may have been obscured by differences in dosing regimens , time off the filter , or altered pharmacokinetics . Conclusions : There is significant variability in antibiotic trough concentrations in critically ill patients receiving continuous renal replacement therapy , which did not only appear to be influenced by effluent flow rate . Here , empirical dosing of antibiotics failed to achieve the target trough antibiotic concentration during 25 % of the dosing intervals A prospect i ve , open-label study investigated the steady-state pharmacokinetics of gatifloxacin in 20 adult patients in a medical Intensive Care Unit ( ICU ) . Twelve patients had normal or moderately impaired renal function ( creatinine clearance ( CrCL ) > or=40 mL/min ) and received gatifloxacin 400 mg intravenously once daily . Eight patients had CrCL<40 mL/min and received 200 mg doses . Gatifloxacin plasma and urine concentrations were determined by vali date d high-performance liquid chromatography . Mean+/-st and ard deviation gatifloxacin elimination half-life ( t(1/2 ) ) , systemic clearance and volume of distribution in patients with CrCL > or=40 mL/min were 10.8+/-1.5h , 156+/-29 mL/min and 1.8+/-0.2 L/kg , respectively . Maximum and minimum serum concentrations ( C(max ) and C(min ) ) and area under the serum concentration-time curve from 0 - 24 h ( AUC(0 - 24 ) ) in these patients were 4.77+/-0.76 mg/L , 1.08+/-0.28 mg/L and 44.4+/-9.2 mgh/L , respectively . Observed t(1/2 ) , C(max ) and AUC(0 - 24 ) following 200 mg doses in patients with poor renal function ( CrCL<40 mL/min ) were 18.2+/-3.3 h , 2.85+/-0.76 mg/L and 36.6+/-3.4 mgh/L , respectively . Statistically significant ( P<0.05 ) increase in AUC(0 - 24 ) and decreases in t(1/2 ) and clearance ( total and renal ) were observed in ICU patients administered intravenous gatifloxacin compared with previous data in healthy volunteers . Pharmacodynamic evaluation by Monte Carlo simulation indicated that approved gatifloxacin dosage regimens appear to be adequate for most pathogens ( minimum inhibitory concentration ( MIC ) < or=0.5 microg/mL ) associated with community-acquired infections in severely ill ICU patients ; less susceptible pathogens ( MIC > or=1 microg/mL ) do not appear to be optimally treated with currently approved doses |
10,398 | 24,510,402 | This finding persists but is weaker when the outcome considered is condom use . | This systematic review examines the relationship between religion and sexual HIV risk behavior .
It focuses primarily on how studies have conceptualized and defined religion , method ologies , and sexual risk outcomes . | Objectives To describe the association between religion and factors related to sexually transmitted diseases (STD)/AIDS in a country where religious leaders were involved early in prevention . Design A cross-sectional study conducted in a rural area in central Senegal . Methods Question naire-based interviews of a r and om sample of 858 adults from the general population aged 15–59 years and in-depth interviews of four religious leaders and 50 people . Results Seventy-six per cent of the respondents were Muslim , 24 % Catholic , 1 % Animist and 0.2 % Protestant . A total of 86 % of men and 87 % of women reported religion to be very important to them . Important prevention-related variables were inversely associated with the importance of religion . Men who considered religion to be very important were less likely to cite AIDS as a major health problem [ odds ratio ( OR ) 0.4 , P = 0.008 ] and were less likely to feel at risk of getting HIV ( OR 0.5 , P = 0.0005 ) . Women who considered religion to be very important were less likely to report an intention to change to protect themselves from AIDS ( OR 0.2 , P = 0.0001 ) , less likely to report having discussed AIDS with others ( OR 0.4 , P = 0.01 ) and much more likely to feel at risk of getting HIV ( OR 9.3 , P = 10−4 ) . Individuals who considered religion to be very important were not more likely to report intending to or actually having become faithful to protect themselves from AIDS . Conclusion These findings stress the need to intensify the involvement of religious authorities in HIV/STD prevention at the local level Environmental influences on sexual behavior are difficult to examine given their temporal distance from the sexual act and the cost of long-term longitudinal studies . We examined environmental influences on risky sexual behavior in young gay men using the Situational Presentation ( Sitpres ) methodology , where situations in which relevant environmental variables are presented as computer vignettes with the variables r and omly allocated , and participants rate the likelihood of their engaging in unsafe sexual behavior . A total of 100 gay men aged between 18 and 26 years of age completed 20 situational presentations with the outcome being the likelihood of engaging in unprotected anal intercourse . On regression analysis , 3 environmental variables significantly predicted safer sex : perceived gay/bisexual men 's norms toward condom use ; availability of HIV prevention messages ; and what one 's religion says about gay sex . Not significant were family , media , legal , and work/school attitudes to homosexuality . Demographic variables that were predictors included education , age , sexual orientation , and degree of being “ out ” about sexual orientation . These data suggest that environmental factors can be approximated using the Sitpres methodology , and that more proximal environmental variables have a stronger impact than distal ones Abstract This paper reports on an exploratory study investigating links between sexual health and social capital in a South African mining community . In this study , social capital is defined in terms of people 's membership of voluntary community organizations ( e.g. church , residents ' associations , youth groups ) . Using biomedical and social survey data from a stratified r and om sample of 1,211 Carletonville residents , we tested the hypothesis that organizational members were less likely to have HIV . Multivariate analysis of variance sought to identify significant associations between nine organizational memberships and HIV infection , as well as three risk factors for infection ( casual partners , condom use with casual partners and alcohol consumption ) . Analysis yielded a range of significant results , but findings varied across age and gender , and were not all in the hypothesized direction . For example , young men and young women who belonged to sports clubs were less likely to be HIV-positive , and young women who belonged to sports clubs were more likely to use condoms with casual partners than non-members . Amongst members of stokvels ( voluntary savings clubs accompanied by social festivities ) , however , young men were more likely to be HIV-positive , women of all ages were more likely to have a casual partner , and both young men and young women were more likely to drink alcohol than non-members . While our exploratory study has produced sufficient evidence to justify the need for further research in this area , it also highlights that the interface between HIV infection and social capital is a complex area that defies easy generalization Objective To study in depth sexual history and sexual behaviour variables as risk factors for HIV-1 infection in a rural Ug and an population . Methods Following a socioeconomic and serological survey of a rural population in Masaka District , south-west Ug and a , 233 r and omly selected HIV-1-positive cases and 233 negative controls matched on age and village of residence , were invited in October 1990 to participate in a case-control study . A total of 132 cases and 161 controls attended for in-depth investigation including an interview about sexual behaviour . Results The factor most strongly associated with increased risk of infection was a greater number of lifetime sexual partners , with odds ratios ( OR ) of 2.1 and 4.9 for those reporting 4–10 and 11 or more partners , respectively , compared with those reporting less than four partners . Having only one sexual partner did not provide complete protection , a total of seven ( one male , six female ) subjects reporting only one sexual partner were HIV-1-positive . Other significant factors were a history of genital ulcers |OR , 2.9 ; 95 % confidence intervals ( CI ) , 1.0–9.1 ) and not being a Muslim ( OR , 5.4 ; 95 % Cl , 1.8–16.5 ) suggesting a possible protective effect of circumcision . There was a suggestion that those who married within the last 7 years ( OR , 2.4 ; 95 % Cl , 0.9–6.1 ) and men exposed to menstrual blood ( OR , 5.7 ; 95 % Cl , 0.7–49.8 ) were at an increased risk of HIV-1 infection . Conclusions These results confirm the predominant role of sexual behaviour in the HIV-1 epidemic . Of particular concern is the observation of HIV-1 infection among those reporting only one partner . Where HIV-1 infection is widely distributed in the general population , risk reduction strategies should , in addition to the promotion of partner reduction , place strong emphasis on safe-sex techniques Whereas college students are not identified as a high-risk group for acquiring the HIV infection , they exhibit high-risk behaviors consistent with their age group , including multiple sexual partners and high rates of unprotected intercourse . This study was conducted to determine levels of HIV-related sexual behavior , along with knowledge and attitudes among students attending community colleges in a relatively affluent multiethnic community . This study used a r and om sample survey ( N = 319 ) of students attending selected classes at four community colleges in Orange County , California , to assess HIV/AIDS knowledge , attitudes , and patterns of past and present sexual behavior . The level of student knowledge concerning HIV disease was found to be relatively high , and pronounced differences in knowledge and sexual permissiveness were identified as a function of ethnicity and religion , with Asians showing lower knowledge and lower concern about HIV , and religion/religiosity related to these variables and also to levels of sexual permissiveness . Respondents ' comfort in asking a partner about his/her sexual history was positively associated with their level of self-esteem , and negatively related to peer pressure in this population . As in previous studies of college population s , HIV knowledge per se does not confer a protective effect against high-risk behavior . However , knowledge was found to be an enabling factor with regard to students ' comfort levels in asking about their partner 's sexual histories , and in requesting that partners take an AIDS test This study set out to investigate the influence of male circumcision and other factors on sexually transmitted infections in Botswana . A syndromic approach , which diagnoses a sexually transmitted infection based on the presence of urethral discharge or genital ulcers rather than on laboratory tests , was used . The data were from the 2001 Botswana AIDS Impact Survey where a nationally representative , r and omly selected sample of men and women aged 10 - 64 years were interviewed in both urban and rural areas . The sample selected for this study consisted of 216,480 men aged 15 - 64 years who had ever had sexual intercourse . The logistic regression technique was executed to examine the association between male circumcision and self-reported urethral discharge or genital ulcers , while controlling for all other independent variables in the analysis . The main finding of this study was that among men who are circumcised , the odds for self-reported urethral discharge or genital ulcers are significantly lower than for those men who are not circumcised in both urban and rural Botswana . The analysis also showed that the odds in favour of self-reported urethral discharge or genital ulcers , for men who drink alcohol , are twice as large as those for men who do not drink alcohol , controlling for all other independent variables in the analysis . Religion and ethnicity also came through as factors exerting a protective influence against self-reported symptoms of sexually transmitted infections . The conclusion is that while male circumcision appears to be significantly associated with the risk for self-reported urethral discharge or genital ulcers , it is man 's behaviour , irrespective of ethnicity or religious dictates , that continues to play a vital role in protection against self-reported symptoms of sexually transmitted infections in Botswana In view of the developmental approach to sexual behavior , this article presents the stages of sexual behavior leading to coitus in four grade s of high school students in Israel and the sociodemographic factors associated with initiating coitus . Analyses were based on data from the first national study dealing comprehensively with sexuality in 30 years . A self-administered question naire was completed by a r and om sample of 4,609 students of the General Educational ( secular ) system that included 68 % of the Hebrew-speaking sector or 55 % of all students in Israel . Our findings indicated a progressive set of stages of sexual behavior forming a Guttman scale , from kissing and petting over the clothes though petting under the clothes and genital touching to coitus . In comparison to results of a 1970 Israeli survey , we found an increase in practice in all Guttman scale stages of sexual behavior , as well as a diminished gap between genders . The gap fully disappeared in the three lower stages . Predictive variables of coitus initiation included gender , religiosity , immigration status , family structure , perceptions of academic achievements , and the proportion of peers practicing coitus . In addition to gender , perception of the proportion of peers that already practice d intercourse was the best predictor followed by grade , perception of academic achievement , and family structure . Marked differences were noticed between genders regarding associations with religiosity and immigration status . The discussion focused on comparisons to findings in other countries , the contribution of the findings to the underst and ing of Israeli adolescents ’ sexual behavior , and practical educational implication OBJECTIVES To assess differences in sexual health behaviors , outcomes , and potential sociocultural determinants among male college students in the United States and the Netherl and s. METHODS Survey data were collected from r and om sample s of students from both national cultures . RESULTS American men were more likely to report inadequate contraception , HIV/STD infection , and unintended pregnancy than were Dutch men . Religiosity and sexuality education were able to explain national differences in these sexual health outcomes . CONCLUSIONS Findings suggest that sexuality education seems to decrease , rather than increase , sexual risk in heterosexually active male college students Background The risk factors for sexually transmitted diseases ( STDs ) and having casual sex among the Chinese people are unknown . Goal The goal of the study was to estimate the prevalence of STDs and to develop a profile of risk behavior among patients attending STD clinics in Hong Kong . Study Design In a clinic-based , cross-sectional study , 448 patients attending two government STD clinics were r and omly sample d and interviewed by means of a structured question naire . Results The prevalence of STDs was 51 % ( 70 % of men and 35 % of women ) . Attendees who had STDs diagnosed were more likely to be male , never married , and smokers and alcohol users ( ever ) and to have had casual sex or sex during travel with someone not their usual partner . Those who did not always use condoms were more likely to be male and never married . Having had casual sex was reported by 63 % of the respondents . Those who reported having had casual sexual encounters were more likely to have the following characteristics : male ; never married ; no religious belief ; ever smoker and alcohol user ; current STD ; had sex during travel ; history of STD ; inconsistent condom user ; and perception of being at low risk for STD . After adjustment , only male gender was associated with casual sexual encounters . Conclusion The results of this study indicated several risk factors among Chinese patients for the acquisition of STDs , for not using condoms , and for having casual sex . This information is useful in strengthening and evaluating currently available STD prevention and control strategies for the Chinese population in Hong Kong and elsewhere Background : Data from sentinel serosurveillance are useful to estimate HIV infection in population s but may not be representative of the general population . General population ‐based surveys attempt to avoid selection bias and are the most appropriate for tracking changes in exposure to risk of HIV infection over time and assessing changes in behavior following prevention campaigns . Objectives : To provide baseline data for targeted sexually transmitted infection ( STI ) and HIV infection prevention interventions by study ing parameters of sexual behavior and knowledge of HIV infection and STIs , measuring health‐seeking behavior related to STIs , and measuring gonorrhea , Chlamydia , syphilis , and HIV‐1 prevalences . Design : Population ‐based survey with stratified sampling by age group from r and omly selected households in a suburb of Mombasa , Kenya . Methods : A st and ard question naire was administered to 1497 consenting adults between the ages of 15 and 49 years who lived in r and omly selected households . Urine and blood sample s were obtained for the estimation of gonorrhea , chlamydial infection , syphilis , and HIV‐1 infection prevalences . Results : Sexual activity in the past 12 months was limited to one partner in all age groups for most sexually active men ( 68 % ) and women ( 88 % ) . More men than women reported two or more partners in the past 12 months ( 23 % vs. 5 % , respectively ) . Almost one half of those persons in the 15‐ to 19‐year‐old age group ( 56 % of boys and 48 % of girls ) were sexually active . Condom use was low with all sexual partners , more so for women than for men . Reported STI symptoms in the past 12 months were high for both men and women . Knowledge of STI symptoms and HIV infection was present but incomplete . Overall HIV seroprevalence was 10.8 % , with significantly higher rates among women ( 13.7 % ) than among men ( 8.0 % ) . HIV seroprevalence in the 15‐ to 19‐year‐old age group was 3.2 % . Female gender , Protestant religion , Catholic religion , and being divorced , separated , and widowed were significantly associated with HIV seroprevalence . Prevalences of gonorrhea , chlamydial infection , and syphilis were 0.9 % , 1.5 % , and 1.3 % , respectively . Conclusions : This study emphasizes the vulnerability of young adults , in particular young women , to HIV infection and the need for intensive interventions in this group . The low use of condoms , incomplete knowledge of HIV infection and STIs , the high number of reported STIs , and the relatively low HIV‐1 seroprevalence among the 15to 19‐year‐old group indicate a large need for intensive STI and HIV infection prevention programs , especially for the 15‐ to 19‐year‐old age group One of the goals of the Acquired Immunodeficiency Syndrome ( AIDS ) control programme in Jamaica is to encourage persons to have a single sex partner . Before this can be achieved in men , it is important to identify the demographic characteristics as well as the sexual attitudes and socialization of men who have multiple sex partners . A national survey was conducted on sexual decision-making in Jamaica in which a r and om sample of 3,001 persons was selected for study and of 2,580 ( 86 % ) interviewed 979 were men . The following analyses included the 769 men who were sexually active . Thirty-four per cent ( 34 % ) , 95 % CI , 30.6 - 37.4 % ) of these men said that they were currently having sex with more than one woman . Although condom use was higher in men with multiple sex partners , 33 % of them said that they never used condoms . Independent predictors of having multiple sex partners were : not being in a stable union ; being raised by fathers only ; and having a secondary school education . There was no significant association with church attendance or with occupation . Compared with other males , men who had multiple sex partners started having sex at an earlier age and were more likely to engage in high-risk sex behaviours such as having sex with prostitutes and abusing drugs prior to coitus . They were also more likely to believe in the use of sex as a means to control their partners and were less likely to think that being married or involved in a long-term relationship was important . These data must be taken into consideration by the AIDS control programme in Jamaica when formulating policies to promote monogamy . There may also be a need to implement parenting support or education programmes for single men who raise their sons Risk factors for HIV-1 infection among women were assessed through a population -based cross-sectional study in the Arusha region of northern Tanzania . The study participants were obtained by r and omly selecting 10-household clusters from Unga limited , the town of Babati , and the roadside village of Matufa , which are urban , semi-urban , and rural communities , respectively . Informed verbal consent for participation in an interview and in HIV-1 testing was sought from each respondent . Blood sample s were collected from each consenting individual for HIV-1 antibody testing using enzyme-linked immunosorbent assay ( ELISA ) , and all positive sera were confirmed using repeated ELISA tests . Information of risk factors was obtained through the interview process using a structured question naire . Of the 567 women who gave blood sample s , 48 ( 8.5 % ) were HIV-1 positive . The HIV-1 seroprevalence rates among women in the urban area , the semi-urban area , and the rural village were 14.4 % , 6.9 % and 2.3 % , respectively . Factors associated with significantly higher HIV-1 seroprevalence were urban residence ; history of having traveled out of the Arusha region within Tanzania , as well as having traveled abroad ; having multiple sex partners ; and having sexual intercourse under the influence of alcohol . Women who reported ever having used condoms had significantly higher probability of being infected with HIV-1 than those who had never used condoms , suggesting that condom use may be a marker of high-risk sexual behavior and that condom use is probably not adhered to in a way that consistently protects against HIV-1 infection . These results suggest the need for health education interventions aim ed at increasing appropriate and consistent condom use and reduction of the number of sexual partners OBJECTIVE To determine the prevalence , incidence , and correlates of HIV-1 infection in a cohort of east African trucking company employees . METHODS HIV-1-seronegative trucking company employees were enrolled in a prospect i ve cohort study and evaluated at 3 monthly intervals for HIV-1 seroconversion , sexually transmitted diseases , and sexual behavior . RESULTS The baseline seroprevalence of HIV-1 among 1500 trucking company employees was 17.8 % . Among 752 HIV-1-seronegative men who were followed , the HIV-1 annual seroincidence was 3.1 % . In univariate analysis , HIV-1 acquisition was associated with age under 25 years , 10 years or less of sexual activity , occupation as a driver/driver 's assistant , occupational travel for more than 14 days per month , religion other than Christian or Muslim , uncircumcised status , sex with a prostitute , sex with a girlfriend/casual partner , extramarital sex , and enrollment seropositivity to Treponema pallidum , Haemophilus ducreyi , and Herpes simplex virus type 2 ( all P values < or = 0.05 ) . Using multivariate analysis , HIV-1 acquisition was independently associated with 10 years or less of sexual activity ( hazard rate ratio ( HRR ) 2.0 , 95 % confidence interval ( CI ) 1.0 - 4.3 ) , occupation as a driver/driver 's assistant ( HRR 3.9 , 95 % CI 1.7 - 9.0 ) , religion other than Christian or Muslim ( HRR 6.1 , 95 % CI 1.4 - 25.7 ) , uncircumcised status ( HRR 2.3 , 95 % CI 1.0 - 5.0 ) , and unprotected sex with a prostitute ( HRR 2.8 , 95 % CI 1.1 - 7.0 ) . CONCLUSIONS Trucking company employees had a high HIV-1 seroprevalence rate at enrollment and a high HIV-1 seroincidence during follow-up . Risk factors for HIV-1 seroconversion included years of sexual activity , occupation , religion , uncircumcised status , and unprotected sex with a prostitute . This population is an appropriate target for HIV-1 prevention trials and behavioral interventions A cross-sectional survey was conducted using interviews among 852 students attending seven secondary schools in the Arusha region , Northern Tanzania , to predict determinants of sexual debut and recent condom use among students . Schools were sample d according to location , school size and ownership criteria . Subjects were r and omly sample d within grade -level and gender through use of class registers . Altogether , 528 students were sexually active . Males were more likely than females to report their sexual debut status ( 82.0 % versus 33.3 % ; OR = 8.78 ; 95 % CI : 6.17 - 12.49 ) . Among males , incidence of sexual debut increased with grade -level , but decreased according to religious affiliation . None of the socio-demographic predictor variables used in this study had a significant association with sexual debut among females when age was controlled for . Of the sexually active students , 26.8 % reported having ever used a condom and 21.5 % reported use of condoms during their most recent sexual encounter . Late sexual debut , prolonged duration of dating before intercourse and having only one sex partner were significantly associated with increased condom use during the most recent occasion . Condom use increased with levels of education , but gender was not significantly linked to increased condom use . Condom use was particularly infrequent among casual sex partners . We observed a marked gender difference among students with respect to their sexual debut status , but no such difference was found in relation to condom use |
10,399 | 15,846,673 | We found a decreasing effect on post-load insulin and no clinical ly relevant effects on lipids or body weight .
Adverse effects were mostly of gastro-intestinal origin and dose dependent .
AUTHORS ' CONCLUSIONS It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes .
Conversely , they have a significant effect on glycemic control and insulin levels , but no statistically significant effect on lipids and body weight .
These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration .
Acarbose dosages higher than 50 mg TID offer no additional effect on glycated hemoglobin but more adverse effects instead .
Compared to sulphonylurea , alpha-glucosidase inhibitors lower fasting and post-load insulin levels and have an inferior profile regarding glycemic control and adverse effects | BACKGROUND Alpha-glucosidase inhibitors such as acarbose or miglitol , have the potential to improve glycemic control in type 2 diabetes mellitus .
The true value of these agents , especially in relation to diabetes related mortality and morbidity , has never been investigated in a systematic literature review and meta- analysis .
OBJECTIVES To assess the effects of alpha-glucosidase inhibitors s in patients with type 2 diabetes mellitus . | OBJECTIVE To compare the safety and efficacy of three doses of acarbose ( 100 , 200 , and 300 mg three times daily ) with placebo for the treatment of non-insulin-dependent diabetes mellitus ( NIDDM ) in patients maintained on dietary therapy alone . RESEARCH DESIGN AND METHODS This multicenter double-blind placebo-controlled trial was 22 weeks in duration . The trial consisted of a 2-week screening period , a 4-week placebo run-in period , and a 16-week double-blind treatment period . The primary measure of drug efficacy was the mean change from baseline in HbA1c levels . Additional efficacy variables included the mean change from baseline in fasting and postpr and ial plasma glucose and serum insulin levels . RESULTS After 16 weeks of treatment , acarbose-treated patients had statistically significant reductions in mean HbA1c levels of 0.78 , 0.73 , and 1.10 % ( relative to placebo ) in the 100- , 200- , and 300-mg t.i.d . groups , respectively . Significant reductions in fasting and postpr and ial plasma glucose levels , glucose area under the time-concentration curve , and maximum glucose concentration were also observed in acarbose-treated patients . Although there were no statistically significant differences among the 100- , 200- , and 300-mg treatment groups , there was a trend toward a dose-response relationship for most plasma glucose variables that were measured . Gastrointestinal side effects ( e.g. , abdominal pain , flatulence , and diarrhea ) and serum transaminase elevations ( e.g. , aspartate aminotransferase [ AST ] and alanine aminotransferase [ ALT ] were more frequently reported in the acarbose-treated patients than in the placebo-treated control patients . Transaminase elevations occurred only at the 200- , and 300-mg dosages and were readily reversible on discontinuation of treatment . CONCLUSIONS Acarbose at doses of 100 , 200 , and 300 mg administered three times daily for 16 weeks significantly reduced HbA1c levels and postpr and ial hyperglycemia . Treatment with acarbose is a safe and effective adjunct to dietary therapy for the treatment of NIDDM Summary The effect of acarbose , an alpha-glucosidase inhibitor , on glycaemic control , was compared with placebo in a double-blind , r and omised , group comparison study during 16 weeks in 20 non-obese non-insulin dependent diabetic patients in whom sulphonylurea treatment had been withdrawn . There was significant deterioration in glycaemic control as assessed by HbA1 following withdrawal of the sulphonylurea . There was no significant improvement in HbA1 between weeks 0 and 16 in either the acarbose ( 11.3 % and 12.4 % respectively ) or the placebo group ( 10.6 % and 12.2 % respectively ) . In both the acarbose and placebo treated groups fasting glucose and insulin concentrations were unaltered . This study also suggests that acarbose was not an effective substitute for sulphonylureas in non-obese Type 2 diabetes uncontrolled by diet alone CONTEXT The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns . OBJECTIVE To evaluate the effect of decreasing postpr and ial hyperglycemia with acarbose , an alpha-glucosidase inhibitor , on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance ( IGT ) . DESIGN , SETTING , AND PARTICIPANTS International , multicenter double-blind , placebo-controlled , r and omized trial , undertaken in hospitals in Canada , Germany , Austria , Norway , Denmark , Sweden , Finl and , Israel , and Spain from July 1998 through August 2001 . A total of 1429 patients with IGT were r and omized with 61 patients ( 4 % ) excluded because they did not have IGT or had no postr and omization data , leaving 1368 patients for a modified intent-to-treat analysis . Both men ( 49 % ) and women ( 51 % ) participated with a mean ( SD ) age of 54.5 ( 7.9 ) years and body mass index of 30.9 ( 4.2 ) . These patients were followed up for a mean ( SD ) of 3.3 ( 1.2 ) years . INTERVENTION Patients with IGT were r and omized to receive either placebo ( n = 715 ) or 100 mg of acarbose 3 times a day ( n = 714 ) . MAIN OUTCOME MEASURES The development of major cardiovascular events ( coronary heart disease , cardiovascular death , congestive heart failure , cerebrovascular event , and peripheral vascular disease ) and hypertension ( > or = 140/90 mm Hg ) . RESULTS Three hundred forty-one patients ( 24 % ) discontinued their participation prematurely , 211 in the acarbose-treated group and 130 in the placebo group ; these patients were also followed up for outcome parameters . Decreasing postpr and ial hyperglycemia with acarbose was associated with a 49 % relative risk reduction in the development of cardiovascular events ( hazard ratio [ HR ] , 0.51 ; 95 % confidence interval [ CI ] ; 0.28 - 0.95 ; P = .03 ) and a 2.5 % absolute risk reduction . Among cardiovascular events , the major reduction was in the risk of myocardial infa rct ion ( HR , 0.09 ; 95 % CI , 0.01 - 0.72 ; P = .02 ) . Acarbose was also associated with a 34 % relative risk reduction in the incidence of new cases of hypertension ( HR , 0.66 ; 95 % CI , 0.49 - 0.89 ; P = .006 ) and a 5.3 % absolute risk reduction . Even after adjusting for major risk factors , the reduction in the risk of cardiovascular events ( HR , 0.47 ; 95 % CI , 0.24 - 0.90 ; P = .02 ) and hypertension ( HR , 0.62 ; 95 % CI , 0.45 - 0.86 ; P = .004 ) associated with acarbose treatment was still statistically significant . CONCLUSION This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension BACKGROUND Acarbose is an oral antidiabetic mainly acting on postpr and ial blood glucose , inhibiting alphaglucosidase . Through this mechanism , it could improve the peripheral insulin sensitivity and /or increase the insulin secretion . The aim of the present study is to assess the therapeutic efficacy of Acarbose in obese type 2 diabetic patients on both insulin resistance and insulin secretion . METHODS 17 obese non insulin-dependent diabetic patients , well controlled with diet alone were r and omized into 2 groups : acarbose ( 2 x 50 mg ) or placebo during 16 weeks . A glucagon test allowed to evaluate insulin secretion before and after treatment as well as a triple test ( glucose-insulin-somatostatin ) with indirect calorimetry allowed to evaluate insulin sensitivity . RESULTS A significant improvement in post-pr and ial plasma glucose was detected only in the Acarbose group ( 8.0 + /- 0.5 mmol/l before vs 6.5 0.5 mmol/l after , p<0.05 ) . Basal C-peptide secretion was similar between groups and remained unchanged after treatment . However , stimulated insulin secretion was significantly increased by 30 % , p<0.05 , in the Acarbose group while no change was detected in the placebo group . Interestingly , the group receiving Acarbose disclosed a 15 % reduction in insulin resistance ( 15.0 + /- 1.8 mmol/l before vs 12.8 + /- 1.4 mmol/l after ) . CONCLUSIONS Our results show that a treatment with Acarbose is efficient even in diabetic patients presenting a good glucose control without any other associated treatment . By decreasing post-pr and ial blood glucose , acarbose improves both insulin sensitivity and secretion Water-extracted Touchi , a traditional Chinese food , exerts a strong inhibitory activity against rat intestinal alpha-glucosidase in foodstuffs , and Touchi-extract ( TE ) has been shown to have an antihyperglycemic effect in rats and humans after a single oral administration . In the present complementary study , the effects of powdered Houji-tea with or without ( placebo ) TE , a formula design ed to enhance good compliance , were monitored in a 3-mo double-blind r and omized group comparison study with placebo controls in humans with borderline and mild type-2 diabetes ( n = 36 ) . All subjects ingested Houji-tea with or without 0.3 g of TE before each of three meals per day for 3 mo . In the TE group , initial fasting blood glucose ( 6.9 + /- 0.1 mmol/L ) and glycated hemoglobin ( HbA(1c ) ; 6.1 + /- 0.1 % ) levels gradually decreased ; fasting blood glucose decreased significantly after 3 mo ( 6.4 + /- 0.3 mmol/L ; P < 0.05 ) as did HbA(1c ) ( 5.6 + /- 0.2 % ; P < 0.01 ) levels at 2 mo postingestion of TE and thereafter . In contrast , fasting blood glucose and HbA(1c ) levels did not change in the placebo group . In this study , other biochemical variables were not affected in any of the subjects , and no one complained of any side effects or abdominal distension . Moreover , there was no deterioration as assessed by fasting blood glucose and HbA(1c ) levels after withdrawal of TE ingestion . Thus , the alpha-glucosidase inhibitory TE demonstrated an antihyperglycemic effect and may prove useful for improving glycemic control in subjects suffering from borderline and type-2 diabetes mellitus The efficacy of the new intestinal alpha-glucosidase inhibitor , miglitol , and glibenclamide were compared in a 6-month double-blind controlled protocol involving 100 non-insulin dependent diabetic patients under diet alone . HbA1c levels ( initially between 7 and 11 % ) were reduced ( p < 0.05 ) : -0.78 + /- 0.21 % after miglitol and -1.18 + /- 0.20 % after glibenclamide . The difference between the two treatments was not significant , although glibenclamide appeared to be more active than miglitol at 8 ( p = 0.002 ) and 16 weeks ( p = 0.01 ) but not at 24 weeks . Fasting glycaemia decreased after miglitol ( 8.7 + /- 0.3 vs 9.6 + /- 0.3 mmol/l , p = 0.005 ) and after glibenclamide ( 8.0 + /- 0.3 vs 9.1 + /- 0.3 , p = 0.007 ) . After miglitol , a decrease was noted after breakfast ( p < 0.001 ) and lunch ( p < 0.001 ) . The same was true for glibenclamide ( p = 0.004 and p < 0.001 respectively ) . A significant reduction in glucose incremental area during a st and ard meal test was noted at the end of miglitol ( p = 0.008 ) or glibenclamide treatment ( p = 0.04 ) . Subgroups of nonresponders to both treatments were identified ( 10/49 with miglitol , 9/47 with glibenclamide ) . Side effects were recorded in 10 patients treated with miglitol ( flatulence and meteorism , diarrhoea , 1 discontinued therapy ) and in 10 treated with glibenclamide ( asthenia , sensation of hunger ) . This study indicates that miglitol is suitable for initial application in diet-resistant Type 2 diabetic patients , providing , a persistent effect and acceptable side effects OBJECTIVE To study the effect of acarbose , an alpha-glucosidase inhibitor , on insulin release and insulin sensitivity in elderly patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Elderly patients with type 2 diabetes were r and omly treated in a double-blind fashion with placebo ( n = 23 ) or acarbose ( n = 22 ) for 12 months . Before and after r and omization , subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study design ed to measure insulin release and sensitivity . RESULTS After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels ( 0.2 + /- 0.3 vs. -0.5 + /- 0.2 mmol/l , placebo vs. acarbose group , respectively ; P < 0.05 ) and in incremental postpr and ial glucose values ( -0.4 + /- 0.6 vs. -3.5 + /- 0.6 mmol/l , placebo vs. acarbose group , P < 0.001 ) between groups . There was a significant difference in the change in HbA(1c ) values in response to treatment ( 0.4 + /- 0.2 vs. -0.4 + /- 0.1 % , placebo vs. acarbose group , P < 0.01 ) . The change in fasting insulin in response to treatment ( -2 + /- 2 vs. -13 + /- 4 pmol/l , placebo vs. acarbose group , P < 0.05 ) and incremental postpr and ial insulin responses ( -89 + /- 26 vs. -271 + /- 59 pmol/l , placebo vs. acarbose group , P < 0.01 ) was also significantly different between groups . During the hyperglycemic clamps , glucose and insulin values were similar in both groups before and after therapy However , there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups ( 0.001 + /- 0.001 vs. 0.004 + /- 0.001 mg/kg x min(-1 ) [pmol/l](-1 ) , respectively , P < 0.05 ) CONCLUSIONS Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes Abstract The aim of this double-blind , placebo-controlled , multinational , five-arm study was to investigate the dose-response relationship of acarbose as a first-line drug in the treatment of type 2 diabetes ( non-insulin dependent ) over a range of minimal and maximal doses according to the European recommendations . The study included 495 patients from 7 countries who were insufficiently controlled with diet alone ( glycosylated haemoglobin HbA1C 6.5%–9 % ) . Acarbose , 25 , 50 , 100 or 200 mg t.i.d . , or placebo t.i.d . was given for 24 weeks . Even a low dosage of 25 mg t.i.d . acarbose reduced fasting and postpr and ial blood glucose levels ( 1 h postpr and ial –11.6 % ; 2 h postpr and ial –11.3 % ) . Acarbose in a dosage of 200 mg t.i.d . had the greatest effect on these parameters . In the placebo group the mean 2 h postpr and ial area under the curve ( AUC ) value for blood glucose was 22.6 mmol/l after 24 weeks ' therapy . The mean 2 h postpr and ial AUC values in the patients given acarbose at doses of 25 , 50 , 100 and 200 mg t.i.d . were found to be 21.2 , 19.6 , 20.3 and 18.5 mmol/l , respectively . The corresponding HbA1C values for the placebo and acarbose groups were 7.83 % , 7.37 % , 7.08 % , 6.98 % and 6.79 % . Interestingly , there was a plateau of blood glucose level at a dosage of 50–100 mg t.i.d . The frequency of flatulence decreased with the duration of drug therapy , but we could not find a linear relationship between doses of acarbose and the gastrointestinal side effects . Less than 3 % of patients stopped tablet intake due to adverse events OBJECTIVE To determine the relationship between carbohydrate intake and the effect of acarbose on HbA1c in subjects with type 2 diabetes treated with acarbose alone , acarbose plus sulfonylurea , acarbose plus metformin , or acarbose plus insulin . RESEARCH DESIGN AND METHODS We conducted a double-blind r and omized placebo-controlled study in which subjects with diabetes in four treatment strata ( 77 on diet alone , 83 treated with metformin , 103 treated with sulfonylurea , and 91 treated with insulin ) were r and omized to treatment with placebo or acarbose for 12 months . Before r and omization , and 3 , 6 , 9 , and 12 months after r and omization , fasting blood was obtained for HbA1c , and 3-day diet records were collected . Subjects who completed at least 6 months of acarbose therapy and provided at least three 3-day diet records were included . RESULTS In the 114 subjects included in this analysis , carbohydrate intake varied from ∼30–60 % of energy . There was no significant relationship between carbohydrate intake and change in HbAlc in any of the four treatment strata ( diet : n = 26 , r = 0.35 , P = 0.076 ; metformin : n = 27 , r = 0.26 , P = 0.19 ; sulfonylurea : n = 35 , r = 0.24 , P = 0.16 ; insulin : n = 25 , r = −0.27 , P = 0.19 ) . In the 80 subjects consuming < 50 % of energy from carbohydrate , the fall in HbAlc ( 7.83 ± 0.17 % at baseline to 6.72 ± 0.13 % on acarbose , P < 0.001 ) was no different from that of the 34 subjects consuming > 50 % of energy from carbohydrate ( 7.55 ± 0.25 % at baseline to 6.66 ± 0.23 % on acarbose , P < 0.001 ) . There was no difference in carbohydrate intake between those who dropped out of the study because of gastrointestinal side effects and those who did not , and there was no relationship between severity of symptoms and the composition of the diet . CONCLUSIONS In subjects with type 2 diabetes consuming 30–60 % of energy from carbohydrate , the effect of acarbose on HbAlc and gastrointestinal symptoms was not related to carbohydrate intake . Because most people consume at least 30 % of energy from carbohydrate , we conclude that no special diet is needed for acarbose to be effective in improving blood glucose control in the treatment of type 2 diabetes BACKGROUND Acarbose delays the release of glucose from complex carbohydrates and disaccharides by inhibiting intestinal alpha-glucosidases , attenuating postpr and ial increments in blood glucose and insulin . This multicenter double-blind study compared the efficacy and safety of acarbose with placebo in the treatment of obese subjects with non-insulin-dependent diabetes mellitus ( NIDDM ) managed by diet . METHODS Two hundred twelve obese subjects with NIDDM who had not received any diabetic medication for at least 12 weeks were r and omized to receive acarbose or placebo . The subjects were stratified by fasting glucose level above or below 11.1 mmol/L ( 200 mg/dL ) . Based on the subject 's therapeutic response and tolerance , the acarbose dosage was titrated from 50 to 300 mg three times per day . This 36-week study consisted of a 6-week pretreatment period , a 24-week double-blind treatment period , and a 6-week posttreatment period . RESULTS Ninety-one subjects given acarbose and 98 subjects who received placebo were evaluable for efficacy . During a st and ard meal tolerance test at the double-blind end point , the differences between treatment groups in mean change from baseline were as follows : 0.9 mmol/L ( 16 mg/dL ) for fasting plasma glucose level , approximately 2.8 mmol/L ( 50 mg/dL ) for postpr and ial plasma glucose level , and 0.59 % ( P < .0001 ) for hemoglobin A1c concentration ( for all three measurements , values decreased in the acarbose group and increased in the placebo group ) . CONCLUSIONS Acarbose improved both fasting and postpr and ial hyperglycemia and improved overall glycemic control as measured by the hemoglobin A1c level . These findings suggest a beneficial role for acarbose in combination with diet in the treatment of obese subjects with NIDDM A double-blind , r and omized , placebo-controlled study was carried out on 44 hypertensive type 2 diabetic subjects previously treated by diet associated or not with sulfonylurea to assess the effects of acarbose-induced glycemic control on blood pressure ( BP ) and hormonal parameters . Before r and omization and after a 22-week treatment period ( 100 to 300 mg/day ) , the subjects were su bmi tted to a st and ard meal test and to 24-h ambulatory BP monitoring ( ABPM ) and had plasma glucose , glycosylated hemoglobin , lipid profile , insulin , proinsulin and leptin levels determined . Weight loss was found only in the acarbose-treated group ( 75.1 + /- 11.6 to 73.1 + /- 11.6 kg , P<0.01 ) . Glycosylated hemoglobin decreased only in the acarbose group ( 6.4 + /- 1.7 to 5.6 + /- 1.9 % , P<0.05 ) . Fasting proinsulin decreased only in the acarbose group ( 23.4 + /- 19.3 to 14.3 + /- 13.6 pmol/l , P<0.05 ) , while leptin decreased in both ( placebo group : 26.3 + /- 6.1 to 23.3 + /- 9.4 and acarbose group : 25.0 + /- 5.5 to 22.7 + /- 7.9 ng/ml , P<0.05 ) . When the subset of acarbose-treated patients who improved glycemic control was considered , significant reductions in diurnal systolic , diastolic and mean BP ( 102.3 + /- 6.0 to 99.0 + /- 6.6 mmHg , P<0.05 ) were found . Acarbose monotherapy or combined with sulfonylurea was effective in improving glycemic control in hypertensive diabetic patients . Acarbose-induced improvement in metabolic control may reduce BP in these patients . Our data did not suggest a direct action of acarbose on insulin resistance or leptin levels This 24-months , placebo-controlled , double-blind , r and omised , group comparison study investigated the effect of acarbose vs placebo for improving metabolic control in patients with Type 2 diabetes under dietary training insufficiently controlled by diet alone . Patients r and omised to acarbose had their dose increased in a stepwise manner to week 5 . From week 5 onwards , they received 100 mg three times daily . This incremental dosing scheme was matched in the placebo group . All patients received specialist , intensive , continuous dietary training and counselling throughout the 2 yr of the study . Of the 74 patients r and omised , 60 were included in the per- protocol analysis ( 28 receiving acarbose ; 32 receiving placebo ) . HbA1c was the primary target variable . Per- protocol analysis found that , after 24 months , the mean difference in HbA1c relative to baseline value was -1.71+/-1.6 % in the acarbose group and -0.82+/-1.1 % in the placebo group . End-point values were 6.85+/-1.7 % in the acarbose group and 7.41+/-1.1 % in the placebo group . This difference between acarbose and placebo was statistically significant ( p=0.02 ) . Patients were defined as responders if they did not require additional treatment with an antidiabetic agent during the study . The responder rate under acarbose therapy was 89 % , compared with 47 % for placebo ( p=0.0005 ) . Acarbose-treated responders improved their HbA1c level to 6.45+/-0.82 % after 24 months . The efficacy of acarbose was consistent throughout the study ; decreasing efficacy was not evident . The results demonstrate the efficacy of acarbose for improving metabolic control in patients with Type 2 diabetes , even when such patients receive good dietary treatment and counselling AIM In a double-blind , placebo-controlled study , we compared the effect of acarbose ( A ) and glibenclamide ( G ) on post-pr and ial ( pp ) and 24-h profiles of proinsulin and insulin . METHODS Twenty-seven patients with Type 2 diabetes mellitus insufficiently controlled with diet alone were r and omised to receive acarbose , 100 mg thrice daily , glibenclamide , 1 mg thrice daily , or placebo . Before and after 16 weeks of treatment , 24-h profiles of proinsulin , insulin and glucose ( fasting , 1 h after breakfast and every 3-h for a 24-h period ) were measured under metabolic ward conditions with st and ardised meals . RESULTS With acarbose , a reduced 24-h level of proinsulin was observed compared with glibenclamide ( AUC 1096 + /- 118 vs. 1604 + /- 174 pmol/l per h , P<0.05 ) at 16 weeks . The breakfast increment of proinsulin was lower with acarbose than glibenclamide ( 6.8 vs. 19.3 pmol/l , P<0.05 ) as was the level at that time ( 37.3 + /- 5.3 vs. 56.4 + /- 7.5 pmol/l , P<0.05 ) . A lower AUC of insulin after treatment was also observed with acarbose than glibenclamide ( 7.9 + /- 0.9 vs. 14.8 + /- 4.5 nmol/l per h , P<0.05 ) , as also for 1-h increment ( 81 + /- 26 , vs. 380 + /- 120 pmol/l , P<0.01 ) and 1-h level ( 325 + /- 30 vs. 621 + /- 132 pmol/l , P<0.01 ) . Acarbose reduced 1-h breakfast glucose increment ( baseline 6.3 + /- 0.6 , 16-week 3.5 + /- 0.6 mmol/l , P<0.01 ) and 1-h glucose level ( 18.1 + /- 1.1 and 14.5 + /- 1.3 mmol/l , P<0.01 ) , whereas glibenclamide did not ( 6.6 + /- 0.7 vs. 5.4 + /- 0.6 mmol/l and 18.9 + /- 1.5 vs. 15.3 + /- 1.3 mmol/l ) . CONCLUSIONS Measurement of circadian excursions of proinsulin and insulin reveals distinct differences in meal-time proinsulin and insulin increment and level between acarbose and glibenclamide whereas fasting levels of these insulin fractions remained unaffected We performed a double blind r and omised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA(1c ) in newly diagnosed patients with type 2 diabetes . Secondary objectives were to compare the effects of both treatments on fasting and post-load blood glucose and insulin levels , lipids , and adverse events . Patients were r and omised to receive acarbose , titrated step-wise to a maximum of 100 mg three times daily ( n=48 ) or tolbutamide , similarly titrated to a maximum of 2000 mg in three doses ( n=48 ) . The two treatments were considered equivalent if the two-sided 90 % confidence interval ( CI ) for the difference in mean HbA(1c ) levels was within the range -0.4 to 0.4 % . Results were analysed on an intention-to-treat , per- protocol and on worst-case basis . Both agents reduced the HbA(1c ) percentage and fasting blood glucose levels . The difference in mean decrease of HbA(1c ) was 0.6 % in favour of tolbutamide ( 90 % CI 0.3 , 0.9 ; 95 % CI 0.2 , 1.0 ) . A worst-case analysis , assuming no change in HbA(1c ) for dropouts , yielded a difference in mean decrease of 0.9 % ( 90 % CI 0.6 , 1.2 ) in favour of tolbutamide . The difference in mean decrease of fasting blood glucose was 1.0 mmol/l in favour of tolbutamide ( 95 % CI 0.3 , 1.7 ) . There were no significant differences in post-load blood glucose , fasting and post-load insulin levels , or lipids . In the acarbose group significantly more patients ( 15 versus 3 ) discontinued therapy because of adverse effects , mostly of gastrointestinal origin . We conclude that the results of this study favour tolbutamide over acarbose as first treatment for patients with newly diagnosed type 2 diabetes OBJECTIVE To examine the impact on metabolic control in NIDDM patients of the alpha-glucosidase inhibitor , acarbose , when administered at a low dose in powdered form . RESEARCH DESIGN AND METHODS Six subjects were recruited for a double-blind cross-over trial using 25 mg powdered acarbose and a placebo 3 times a day with meals for 3 mo . In addition to parameters of diabetes control and body weight , glucose turnover and insulin sensitivity were measured with the hyperinsulinemic/euglycemic clamp technique combined with tracer kinetics . RESULTS None of the subjects showed significant changes in FPG levels or body weight either on the 3-mo course of acarbose or placebo . HbA1c fell significantly from 10.6 ± 1.0 to 9.4 ± 1.3 % ( P = 0.05 ) during treatment with acarbose but failed to change on placebo ( 10.1 ± 1.0 to 11.1 ± 2.0 % ; P = 0.36 ) . Basal HGP and glucose utilization were unchanged during either of the treatment periods , and hyperinsulinemia produced a similar degree of suppression of HGP before and after each treatment . At a physiological concentration , insulin failed to stimulate glucose clearance in these diabetic patients , and no improvement was seen with acarbose treatment . No changes in plasma lipids or lipoprotein profiles were demonstrated after 3 mo on acarbose . In acute studies , it was shown that administration of acarbose at a dose of 25 mg powder per meal significantly decreased the postpr and ial glycemic excursion . CONCLUSIONS When administered in the powdered form at the low dose of 25 mg 3 times/day with meals over 3 mo , acarbose was well tolerated by the NIDDM patients and was without side effects . It improved glycemic control by reducing postpr and ial hyperglycemia , but had no effect on glucose turnover , insulin sensitivity , or lipid profile OBJECTIVE To investigate the efficacy and safety of miglitol in combination with metformin in improving glycemic control in out patients in whom type 2 diabetes is insufficiently controlled by diet alone . RESEARCH DESIGN AND METHODS In this multicenter , double-blind , placebo-controlled study , 324 patients with type 2 diabetes were r and omized , after an 8-week placebo run-in period , to treatment with either placebo , miglitol alone , metformin alone , or miglitol plus metformin for 36 weeks . The miglitol was titrated to 100 mg three times a day and metformin was administered at 500 mg three times a day . The primary efficacy criterion was change in HbA(1c ) from baseline to the end of treatment . Secondary parameters included changes in fasting and postpr and ial plasma glucose and insulin levels , serum triglyceride levels , and responder rate . RESULTS A total of 318 patients were valid for intent-to-treat analysis . A reduction in mean placebo-subtracted HbA(1c ) of -1.78 % was observed with miglitol plus metformin combination therapy , which was significantly different from treatment with metformin alone ( -1.25 ; P = 0.002 ) . Miglitol plus metformin also result ed in better metabolic control than metformin alone for fasting plasma glucose ( -44.8 vs. -20.4 mg/dl ; P = 0.0025 ) , 2-h postpr and ial glucose area under the curve ( -59.0 vs. -18.0 mg/dl ; P = 0.0001 ) , and responder rate ( 70.6 vs. 45.52 % ; P = 0.0014 ) . All therapies were well tolerated . CONCLUSIONS In type 2 diabetic patients , miglitol in combination with metformin gives greater glycemic improvement than metformin monotherapy AIMS A double-blind r and omised study was performed to compare the dose-effect and dose-tolerability relationships between the alpha-glucosidase inhibitor miglitol in doses of 25 mg , 50 mg , 100 mg and 200 mg all t.i.d . vs placebo t.i.d . in patients with Type 2 diabetes mellitus on diet only . METHODS After a 6-week placebo run-in period 468 patients with a fasting blood glucose > or = 7 mmol/l as well as a HbA1c between 6.1 % and 10.4 % were r and omised for a 24-week treatment period . RESULTS The results of 465 patients were valid for safety analysis and of 384 patients for the efficacy analysis . In the placebo group the HbA1c level increased by 0.40+/-1.46 % as compared with baseline . The decrease in the mean HbA1c values ( corrected for differences in baseline values ) was significant and dose-dependent for all miglitol groups compared with placebo , being -0.46 % ( 95 % CI : -0.91 % , -0.01 % ) in the 25 mg group , -0.45 % ( 95 % CI : -0.90 % , -0.003 % ) in the 50 mg group , -0.84 % ( 95 % CI : -1.31 % , -0.37 % ) in the 100 mg group and -1.26 % ( 95 % CI : -1.76 % , -0.76 % ) in the 200 mg group . Blood glucose levels following a st and ardised breakfast tolerance test were significantly and dose-dependently lower for all the miglitol doses at 12 and 24 wk of treatment compared to baseline : in comparison with baseline maximum blood glucose increased by 4 % with placebo and decreased by 7 % , 14 % , 24 % and 33 % with miglitol 25 mg , 50 mg , 100 mg and 200 mg t.i.d . respectively . The same pattern was seen with postpr and ial maximal serum insulin levels which decreased by 8 % under placebo and by 17 % , 26 % , 25 % and 35 % with the 25 mg to 200 mg doses of miglitol . The adverse events reported were mainly of gastrointestinal nature , mostly being flatulence , diarrhoea and abdominal pain and the incidence increased with increasing dose . Although the side effects were not serious , they were troublesome , leading to a considerable drop-out rate increasing with dose . CONCLUSIONS The alpha-glucosidase inhibitor miglitol in Type 2 diabetic patients on diet alone decreases both HbA1c levels and postpr and ial glucose and insulin levels in a dose-dependent manner . Gastrointestinal side effects also showed dose-dependency . Combination of efficacy and safety results leads to the conclusion that the optimal dose of miglitol will be in the range of 50 to 100 mg t.i.d OBJECTIVE To assess the efficacy , safety , and tolerability of acarbose versus placebo during a 24-week treatment period in Asian type 2 diabetic patients with dietary failure . RESEARCH DESIGN AND METHODS After a 6-week screening period , 126 multiethnic Asian type 2 diabetic patients ( 64 men , 62 women ; mean age ± SD , 53.4 ± 10 years ) were r and omized to receive acarbose ( n = 63 ) or placebo ( n = 63 ) . The dosage was increased from 50 mg t.i.d . at week 0 to 100 mg t.i.d . at week 4 . Patients were then followed up at weeks 10 , 16 , and 24 . At each visit , body weight , blood pressure , and metabolic indexes were measured . At weeks 0 and 24 , fasting plasma glucose and insulin were measured before and 1 h after the administration of an individually tailored breakfast . RESULTS Using the intention-to-treat analysis , there were greater reductions in ( mean [ 95 % CI ] ) HbA1c ( −0.70 [ −1.00 to −0.39 ] vs. −0.27 % [ −0.54 to 0 ] ; P = 0.04 ) , fasting plasma glucose ( −0.37 [ −0.75 to 0.02 ] vs. 0.41 mmol/1 [ −0.08 to 0.90 ] ; P = 0.017 ) and 1-h plasma glucose ( −0.77 [ −1.44 to −0.10 ] vs. 0.65 mmol/1 [ −0.07 to 1.36 ] ; P = 0.05 ) in the acarbose group compared with the placebo group . With acarbose treatment , 78 % of patients achieved an HbA1c < 8 % compared with 56 % in the placebo group ( P = 0.003 ) . There was a greater reduction in body weight ( −1.31 [ −2.46 to −0.15 ] vs. 0.16 kg [ −3.36 to 0.10 ] ; P = 0.02 ) and higher incidence of flatulence ( 56 vs. 37 % ; P = 0.032 ) in the acarbose than in the placebo group . Using baseline HbA1c and race as covariates , there were no significant interethnic differences in treatment responses ( P = 0.232 for treatment-race interaction ; P < 0.001 for treatment effect ) . The dropout rates were similar between the two groups ( acarbose , 11 of 63 ; placebo , 6 of 63 ) . There were no significant laboratory adverse events in either group . CONCLUSIONS In this multicenter study involving six ethnic groups , acarbose 100 mg t.i.d . was an effective , safe , and generally well-tolerated therapy in Asian type 2 diabetic patients with dietary failure . In some patients with troublesome gastrointestinal symptoms , a lower dosage may be necessary Post-pr and ial glucose excursions remain elevated in most patients with diabetes even when normal fasting plasma glucose levels have been achieved . In 39 patients with type 2 diabetes who had attained basal normoglycaemia by therapy with diet alone , a sulphonylurea , a basal insulin supplement or basal plus pr and ial insulin the mean glycosylated haemoglobin ( HbA1 ) values were at the upper end ( mean + /- 1SD , 8.1 + /- 1.1 % ) of the normal range ( 5.0 - 8.2 % ) . Miglitol , an alpha-glucosidase inhibitor , given in a dose of 50 mg three times a day was studied in a double blind r and omized crossover study . In diet and sulphonylurea treated patients , a mean 25 % reduction of the post-pr and ial plasma glucose excursions was obtained whereas in ultralente treated patients miglitol appeared to reduce basal plasma glucose levels ( p < 0.006 ) . Side effects were limited to minor gastrointestinal disturbances , usually ameliorating after the first week of therapy . Alpha-glucosidase inhibition to prevent post-pr and ial glycaemia may have a role in patients in whom sulphonylurea or diet therapy has been used to obtain normal basal glucose concentrations This study compared the effects of acarbose plus glibenclamide combination therapy with acarbose or glibenclamide treatment alone on postpr and ial blood glucose , serum insulin and C-peptide levels , and the tendency to develop hypoglycaemia . A total of 84 patients with Type 2 diabetes ( fasting blood glucose : 120 - 180 mg/dl ; postpr and ial blood glucose : 140 - 240 mg/dl ) was included in this two-centre , double-blind , double-dummy , placebo-controlled study . Patients were r and omised to one of 4 treatment groups : acarbose ( 100 mg ) ; glibenclamide ( 3.5 mg ) ; acarbose plus glibenclamide ; or placebo . Treatment was administered before a st and ard breakfast , and fasting ( 07.30 h , 08.00 h ) and postpr and ial ( 09.00 , 10.00 , 11.00 , 12.00 h ) blood glucose , serum insulin and C-peptide levels were determined . Acarbose plus glibenclamide treatment significantly reduced the mean increase in postpr and ial blood glucose levels ( 23.7+/-17.3 mg/dl ) compared with either acarbose ( 58.4+/-31.6 mg/dl ) , glibenclamide ( 56.9+/-42.8 mg/dl ) or placebo ( 101.6+/-49.2 mg/dl ) ( p<0.05 for all ) . Serum insulin levels ( mean AUC(7.30 - 12 h ) ) observed with acarbose plus glibenclamide combination therapy were significantly lower than those observed with glibenclamide monotherapy ( 243.5+/-161.1 vs 383.4+/-215.8 hr x microU/ml ; p=0.02 ) , and comparable with the values seen with placebo ( 226.0+/-166.6 hr x microU/ml ) , suggesting that acarbose modifies the insulin secretion induced by glibenclamide . Glibenclamide monotherapy result ed in a significantly higher rate of decrease in blood glucose level than with acarbose plus glibenclamide ( 71.8+/-29.9 vs 46.2+/-18.0 mg/dl x h(-1 ) ; p=0.0003 ) , and blood glucose levels at 11.00 h were also markedly lower with glibenclamide ( 84.4+/-29 mg/dl ) than acarbose plus glibenclamide ( 102.0+/-41 mg/dl ) , suggesting a reduced tendency for hypoglycaemic episodes with acarbose plus glibenclamide than with glibenclamide alone . In all , 6 ( 29 % ) hypoglycaemic episodes occurred with glibenclamide , 2 ( 10 % ) with acarbose plus glibenclamide and none with acarbose . Acarbose plus glibenclamide combination therapy results in an additive glucose lowering effect and reduced risk for hypoglycaemia . Acarbose modifies the insulin secretion induced by glibenclamide , which explains the lower risk of hypoglycaemia compared with glibenclamide monotherapy This study evaluated the efficacy of acarbose in improvement of metabolic control in patients with fairly , well controlled non-insulin-dependent diabetes mellitus ( NIDDM ) . Fifteen patients with mean age and duration of diabetes of 57.5 + /- 2.6 ( SE ) and 7.5 + /- 1.5 years , respectively were recruited and completed our study protocol . This study was a double-blind , crossover , placebo-controlled design consisting of two twelve-week treatments of acarbose and placebo separated by an eight-week washout period . Acarbose was effective in lowering of 1-hour and 2-hour postpr and ial plasma glucose from 251.7 + /- 10.7 and 205.3 + /- 9.1 mg/dl to 197.4 + /- 7.0 ( p = 0.001 ) and 181.5 + /- 8.5 mg/dl ( p = 0.03 ) , respectively . Fasting plasma glucose was slightly decreased but without significant change , from 150.8 + /- 7.3 to 140.8 + /- 6.1 mg/dl ( p = 0.07 ) . Overall glycemic control tended to improve during the study period as indicated by the falling of HbA1c levels from 7.7 + /- 0.4 to 7.0 + /- 0.2 per cent ( p = 0.05 ) . Serum C-peptide both fasting and postpr and ial as well as serum lipids were not affected by acarbose . Almost half of the patients treated with acarbose had mild and tolerable gastrointestinal adverse effects . In conclusion , acarbose , as combined therapy with other oral hypoglycemic agents , was effective in improvement of glycemic control particularly postpr and ial hyperglycemia in fairly , well controlled NIDDM patients with mild and acceptable adverse effects BACKGROUND The worldwide increase in type 2 diabetes mellitus is becoming a major health concern . We aim ed to assess the effect of acarbose in preventing or delaying conversion of impaired glucose tolerance to type 2 diabetes . METHODS In a multicentre , placebo-controlled r and omised trial , we r and omly allocated patients with impaired glucose tolerance to 100 mg acarbose or placebo three times daily . The primary endpoint was development of diabetes on the basis of a yearly oral glucose tolerance test ( OGTT ) . Analyses were by intention to treat . FINDINGS We r and omly allocated 714 patients with impaired glucose tolerance to acarbose and 715 to placebo . We excluded 61 ( 4 % ) patients because they did not have impaired glucose tolerance or had no postr and omisation data . 211 ( 31 % ) of 682 patients in the acarbose group and 130 ( 19 % ) of 686 on placebo discontinued treatment early . 221 ( 32 % ) patients r and omised to acarbose and 285 ( 42 % ) r and omised to placebo developed diabetes ( relative hazard 0.75 [ 95 % CI 0.63 - 0.90 ] ; p=0.0015 ) . Furthermore , acarbose significantly increased reversion of impaired glucose tolerance to normal glucose tolerance ( p<0.0001 ) . At the end of the study , treatment with placebo for 3 months was associated with an increase in conversion of impaired glucose tolerance to diabetes . The most frequent side-effects to acarbose treatment were flatulence and diarrhoea . INTERPRETATION Acarbose could be used , either as an alternative or in addition to changes in lifestyle , to delay development of type 2 diabetes in patients with impaired glucose tolerance OBJECTIVE To hypothesize if glibenclamide , which increases insulin levels , also increases leptin concentrations . RESEARCH DESIGN AND METHODS Leptin is a hormone that regulates weight in mice . In obese humans , leptin concentrations are increased , suggesting resistance to the effects of this hormone . Although short-term infusion of insulin during the hyperinsulinemiceuglycemic clamp does not increase leptin concentration , the effect of oral antidiabetic agents on leptin concentration is unknown . Differing effects can be expected , since glibenclamide acts via stimulation of insulin secretion , whereas acarbose inhibits alpha-glucosidases of the small intestine and has no direct effect on insulin levels . We examined the effect of acarbose ( n = 4 ) , glibenclamide ( n = 6 ) , and placebo ( n = 6 ) on insulin and leptin levels during 24-h periods before and after 16 weeks of therapy . RESULTS We observed a significant diurnal variation in leptin concentrations . This was inversely related to insulin levels during the 24-h follow-up with usual diet . Neither the placebo nor acarbose altered leptin concentrations . However , glibenclamide increased leptin concentrations parallel to insulin levels . There were only minor changes in body weight during the l6-week follow-up : decrease in the placebo group ( change −0.5 kg/m2 , P = 0.07 ) and acarbose ( change −0.7 kg/m2 , P = 0.046 ) and increase in the glibenclamide group ( change 0.8 kg/m2 , P = 0.27 ) . However , individual subjects who gained weight had increases in their leptin concentrations . The diurnal variation in leptin concentrations was preserved after glibenclamide . CONCLUSIONS Glibenclamide increases circadian leptin and insulin concentrations , whereas acarbose does not . This observation may help to explain weight gain in subjects treated with glibenclamide and stable weight in those treated with acarbose in the long run Acarbose ( Bay g 5421 , Glucobay ; CAS 56180 - 94 - 0 ) inhibits alpha-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates . It is therefore efficient as a first-line drug in the treatment of noninsulin-dependent diabetics ( NIDDM ) insufficiently treated with diet alone . Information is scarce whether under acarbose treatment the lipid metabolism can also be improved . Therefore the changes of triglycerides , cholesterol and HDL-cholesterol were analyzed in a r and omized double-blind placebo-controlled trial . In brief , 94 NIDDM aged 43 to 70 , after a pretreatment period of at least 3 months , were treated with 100 mg acarbose t.i.d . or placebo for 24 weeks . The patients were recruited after a 4-week screening phase with reinforcement of diet . The most impressive results of acarbose treatment were lowering of blood glucose and insulin , especially in the postpr and ial state , and of HbA1 ( glycosylated hemoglobin ) . Results on lipids : The initial serum cholesterol levels showed a broad spectrum . Low concentrations remained unchanged under acarbose , while high concentrations ( the upper tercile ) decreased from 273 to 251 mg/dl . This effect was statistically significant compared to placebo . HDL-cholesterol levels increased continuously under acarbose and placebo as well thus indicating some study effect . Similarly , fasting triglycerides leveled down under acarbose and placebo . However , drastic differences appeared in postpr and ial triglycerides which were checked 1 and 5 h after a test meal given at entry and at finish of the study . The lowering by acarbose compared to placebo was highly significant for the 1 h postpr and ial concentrations . It is concluded that acarbose treatment can reduce elevated cholesterol concentrations and postpr and ial triglyceride concentrations . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES : To see if the long-term treatment of non-insulin dependent diabetes ( NIDDM ) with the α-glucosidase inhibitor acarbose affects food intake and body weight . DESIGN : R and omized , double-blind , placebo-controlled , parallel design clinical trial of 12 months duration . SUBJECTS : Subjects with NIDDM in four treatment strata : 77 on diet alone , 83 also treated with metformin , 103 also treated with sulfonylurea and 91 also treated with insulin . MEASUREMENTS : Two 3 day diet records were obtained before r and omization to acarbose or placebo therapy , and additional 3 day diet records were obtained at 3 , 6 , 9 and 12 months after r and omization . Body weight was also measured at these times . RESULTS : Of the 354 subjects r and omized , 279 ( 79 % ) completed at least 9 months of therapy and , of these , 263 ( 94 % ) provided at least one diet record during the baseline period and two diet records during the treatment period . After one year , subjects on acarbose had lost 0.46±0.28 kg , which differed significantly from the 0.33±0.25 kg weight gain on placebo ( P=0.027 ) . The difference in weight change between acarbose and placebo did not differ significantly in the different treatment strata . Being in the study had significant effects on diet , including a reduction in energy intake from 1760–1700 Kcal/d ( P<0.05 ) , a reduction in simple sugars intake from 18.5–17.4 % of energy ( P<0.001 ) , and reductions in the number of different foods consumed ( 33–30 , P<0.001 ) and the number of meals eaten per day ( 4.7–4.3 , P<0.001 ) . However , compared to placebo treatment , acarbose had no effect on energy intake , nutrient intakes , or dietary patterns . CONCLUSIONS : In subjects with NIDDM on weight-maintaining diets , long-term acarbose therapy results in a small weight loss , but has no effect on energy or nutrient intakes . The weight loss induced by acarbose may be due partly to reduced doses of concomitant oral agents and insulin and partly to energy loss due to increased colonic fermentation OBJECTIVE To determine the degree to which alpha-glucosidase inhibitors , with their unique mode of action primarily reducing postpr and ial hyperglycemia , offer an additional therapeutic approach in the long-term treatment of type 2 diabetes . RESEARCH DESIGN AND METHODS We studied 1,946 patients ( 63 % men ) who were previously enrolled in the U.K. Prospect i ve Diabetes Study ( UKPDS ) . The patients were r and omized to acarbose ( n = 973 ) , titrating to a maximum dose of 100 mg three times per day , or to matching placebo ( n = 973 ) . Mean + /- SD age was 59 + /- 9 years , body weight 84 + /- 17 kg , diabetes duration 7.6 + /- 2.9 years , median ( interquartile range ) HbA1c 7.9 % ( 6.7 - 9.5 ) , and fasting plasma glucose ( FPG ) 8.7 mmol/l ( 6.8 - 11.1 ) . Fourteen percent of patients were treated with diet alone , 52 % with monotherapy , and 34 % with combined therapy . Patients were monitored in UKPDS clinics every 4 months for 3 years . The main outcome measures were HbA1c , FPG , body weight , compliance with study medication , incidence of side effects , and frequency of major clinical events . RESULTS At 3 years , a lower proportion of patients were taking acarbose compared with placebo ( 39 vs. 58 % , P < 0.0001 ) , the main reasons for noncompliance being flatulence ( 30 vs. 12 % , P < 0.0001 ) and diarrhea ( 16 vs. 8 % , P < 0.05 ) . Analysis by intention to treat showed that patients allocated to acarbose , compared with placebo , had 0.2 % significantly lower median HbA1c at 3 years ( P < 0.001 ) . In patients remaining on their allocated therapy , the HbA1c difference at 3 years ( 309 acarbose , 470 placebo ) was 0.5 % lower median HbA1c ( 8.1 vs. 8.6 % , P < 0.0001 ) . Acarbose appeared to be equally efficacious when given in addition to diet alone ; in addition to monotherapy with a sulfonylurea , metformin , or insulin ; or in combination with more complex treatment regimens . No significant differences were seen in FPG , body weight , incidence of hypoglycemia , or frequency of major clinical events . CONCLUSIONS Acarbose significantly improved glycemic control over 3 years in patients with established type 2 diabetes , irrespective of concomitant therapy for diabetes . Careful titration of acarbose is needed in view of the increased noncompliance rate seen secondary to the known side effects OBJECTIVE To assess the long-term safety and effectiveness of a titrated dose of the alpha-glucosidase inhibitor miglitol ( BAY m 1099 ) in Hispanic NIDDM patients . RESEARCH DESIGN AND METHODS A 1-year double-blind r and omized placebo-controlled study in which diet-treated or diet plus sulfonylurea-treated Hispanic NIDDM patients received either placebo ( n = 131 ) or miglitol in doses of 50 , 100 , 150 , 200 mg t.i.d . ( n = 254 ) , up-titrated and down-titrated based on tolerability . Efficacy parameters included changes from baseline in HbA1c , fasting and 2-h postpr and ial plasma glucose and serum insulin , fasting serum lipids , and urinary albumin-to-creatinine ratio ( ACR ) . Safety assessment s consisted primarily of tabulation of adverse events and intercurrent illnesses , and of periodic laboratory determinations . RESULTS Reductions from baseline in HbA1c levels at the 6-month ( primary efficacy ) endpoint were significantly greater by 0.83 % in the miglitol group than in the placebo group . HbA1c reductions in the miglitol treatment group significantly exceeded those in the placebo group by 0.63 , 0.73 , and 0.92 % at 3 , 9 , and 12 months of treatment , respectively . Reductions in 120-min postpr and ial glucose and insulin levels were significantly greater in the miglitol group than in the placebo group at all postbaseline visits . There was little difference between treatments for changes in fasting insulin or lipid levels . Miglitol-associated reductions versus placebo in fasting plasma glucose ( P = 0.0587 at 6 months ) and in ACR ( P = 0.0541 at 1-year ) were nearly statistically significant . These efficacy results were not notably different between the 6-month endpoint , at which time the mean miglitol dose was 100 mg t.i.d . , and the 1-year visit , when the mean miglitol dose was 149 mg t.i.d . Notable adverse events seen significantly more often in the miglitol group than in the placebo group were flatulence and diarrhea ( or soft stools ) . The incidence of these gastrointestinal adverse events appeared to be dose dependent . CONCLUSIONS Miglitol treatment of non-insulin-requiring Hispanic NIDDM patients at doses from 50 to 200 mg t.i.d . produced statistically and clinical ly significant reductions of HbA1c , primarily associated with reduction of glucose and insulin levels in the postpr and ial period , which were sustained over a year of treatment . Adverse events related to the drug 's mechanism of action were common , but generally well tolerated . Doses above 100 mg t.i.d . were not associated with notably enhanced efficacy in most patients OBJECTIVE To determine whether a forced titration of acarbose ( from 50 to 300 mg three times daily ) administered over a 24-week period , in conjunction with diet and insulin therapy , improves glycemic control and reduces daily insulin requirements in insulin-requiring type II diabetes . RESEARCH DESIGN AND METHODS This multicenter , r and omized , double-blind , placebo-controlled trial was 36 weeks in duration . The trial consisted of a 6-week pretreatment period , a 24-week double-blind treatment period , and a 6-week post-treatment follow-up period . The primary efficacy variables were the mean change from baseline in HbA1c levels and the mean percentage change from baseline in total daily insulin dose . RESULTS Treatment with acarbose was associated with significant reductions in HbA1c levels of 0.40 % ( P = 0.0001 ) and in total daily insulin dose of 8.3 % ( P = 0.0015 ) . There were also significant reductions in all plasma glucose variables measured , including a 0.9 mmol/l reduction in fasting glucose ( P = 0.0440 ) , a 2.6 mmol/l reduction in glucose Cmax ( P = 0.0001 ) and a 270 mmol·min−1·l−1 reduction in glucose area under the curve ( P = 0.0002 ) . Although acarbose treatment was associated with a greater incidence of adverse events than was placebo treatment , primarily flatulence and diarrhea , these events did not generally prevent patients from completing the study . CONCLUSIONS The results of this study suggest that acarbose is a safe and effective adjunct to diet and insulin therapy for the management of insulin-requiring type II diabetes OBJECTIVE To compare the different therapeutic principles of α-glucosidase inhibitors and sulphonylureas as first-line treatment in non-insulin-dependent diabetes mellitus ( NIDDM ) patients with dietary failure . RESEARCH DESIGN AND METHODS Ninety-six NIDDM patients ( 35–70 years of age , body mass index [ BMI ] ≤ 35 ) , insufficiently treated with diet alone ( HbA1c 7–9 % ) were r and omized into three groups and treated for 24 weeks with acarbose , glibenclamide , or placebo . Efficacy , based on fasting blood glucose ( BG ) , BG 1 h after ingestion of st and ard breakfast ( postpr and ial ) , serum insulin , postpr and ial insulin increase , and HbA1c ; and tolerability , based on subjective symptoms and laboratory values , were investigated every 6 weeks . Efficacy evaluation was valid for 85 patients . RESULTS The test drugs were dosed as follows : 100 mg acarbose ( A ) three times a day , 1 placebo tablet three times a day , 3.5 mg glibenclamide tablets dosed 1–0 - 0 or 1–0 - 1 , mean dose 4.3 mg/day . Compared with the placebo , both drugs showed the same mean efficacy on fasting BG ( –1.4 raM with acarbose , –1.6 mM with glibenclamide ) , 1-h postpr and ial BG ( –2.2 mM with acarbose , –1.9 mM with glibenclamide ) , and HbA1c ( –1.1 % with acarbose , –0.9 % with glibenclamide ) ; but they showed a marked difference in 1-h postpr and ial insulin values ( –80.7 pM with acarbose , 96.7 pM with glibenclamide ) . The mean relative insulin increase ( 1-h postpr and ial ) was 1.5 in the placebo group , 1.1 in the acarbose group , and 2.5 in the glibenclamide group . No changes in body weight could be observed . No adverse events were seen under placebo . Acarbose led to mild or moderate intestinal symptoms in 38 % of patients . Glibenclamide led to hypoglycemia , which could be solved by dose reduction , in 6 % of patients . No dropouts occurred in any of the treatment groups . CONCLUSIONS Acarbose and glibenclamide are effective drugs for the monotherapy of NIDDM patients when diet alone fails . Because postpr and ial insulin increase has been shown to be associated with increased risk for cardiovascular disease , acarbose , which lowers pp increase , may be superior to glibenclamide , which elevates postpr and ial insulin increase PURPOSE To compare the therapeutic potential of acarbose , metformin , or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . PATIENTS AND METHODS Ninety-six patients with NIDDM ( 35 - 70 years of age , body mass index ( BMI ) < or = 35 kg/m2 , insufficiently treated with diet alone , glycated hemoglobin ( HbA1c ; 7 % to 11 % ) were r and omized into 3 groups and treated for 24 weeks with acarbose , 3 x 100 mg/day , or metformin , 2 x 850 mg/day , or placebo . Efficacy , based on HbA1c ( primary efficacy criterion ) , fasting blood glucose ( BG ) and insulin , 1 hour postpr and ial BG and insulin ( after st and ard meal test ) , postpr and ial insulin increase , plasma lipid profile , and tolerability , based on subjective symptoms and laboratory values were determined every 6 weeks . Analysis of covariance was performed for endvalues with adjustment on baseline values . Ninety-four patients were valid for efficacy evaluation . RESULTS Both active drugs showed the same improvement of efficacy criteria compared with placebo . Baseline adjusted means at endpoint were as follows : BG , fasting and 1 hour postpr and ial , 9.2 mM and 10.9 mM with placebo , 7.6 mM and 8.7 mM with acarbose , and 7.8 mM and 9.0 mM with metformin ; HbA1c was 9.8 % with placebo , 8.5 % with acarbose , and 8.7 % with metformin . Comparisons : acarbose versus placebo and metformin versus placebo were statistically significant , but not acarbose versus metformin . No effect on fasting insulin could be observed . Relative postpr and ial insulin increase was 1.90 with placebo , 1.09 with acarbose , and 1.03 with metformin . Comparisons : acarbose versus placebo and metformin versus placebo were statistically significant , but not acarbose versus metformin . With respect to lipid profile , acarbose was superior to metformin . Low-density lipoprotein (LDL)/high-density lipoprotein ( HDL ) cholesterol ratio increased by 14.4 % with placebo , was unchanged with metformin , but decreased by 26.7 % with acarbose . Comparisons : acarbose versus placebo and acarbose versus metformin were statistically significant , but not metformin versus placebo . Slight body weight changes were observed with acarbose ( -0.8 kg ) and metformin ( -0.5 kg ) , but not with placebo . Acarbose led to mild or moderate intestinal symptoms in 50 % of the patients within the first 4 weeks , but in only 13.8 % of the patients within the last 4 weeks . CONCLUSIONS Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM . With respect to plasma lipid profile , especially HDL cholesterol , LDL cholesterol and LDL/HDL cholesterol ratio acarbose may be superior to metformin AIMS To study the effect of acarbose , an alpha-glucosidase inhibitor , on glycemic control in elderly patients with type 2 diabetes . METHODS Elderly patients with type 2 diabetes treated with diet alone were r and omly treated in a double-blind fashion with placebo ( n=99 ) or acarbose ( n=93 ) for 12 months . RESULTS After 12 months of therapy , there was a statistically significant difference in the change in glycated haemoglobin ( HbA(1c ) ) ( -0.6 % ) in the acarbose group versus placebo , as well as in the incremental post-pr and ial glucose values ( -2.1 mmol h/l ) and mean fasting plasma glucose ( -0.7 mmol/l ) . Although there was no effect of acarbose on insulin release , there was a clear effect of acarbose to decrease relative insulin resistance ( -0.8 ) ( HOMA method ) . In addition , acarbose was generally well tolerated and safe in the elderly ; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea . There were no cases of hypoglycemia reported , and no clinical ly relevant changes in laboratory abnormalities or vital signs during the study . CONCLUSIONS Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone 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 Objecative Acarbose inhibits α-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates . Therefore , its efficacy and acceptability as a first-line drug in non-insulin-dependent diabetes mellitus ( NIDDM ) insufficiently treated with diet alone was tested in a r and omized double-blind placebo-controlled study . Research Design And Methods Ninety-four NIDDM subjects , aged 43–70 yr with average body mass index of 28 kg/m2 and undergoing a pretreatment period of at least 3 mo with diet alone , were treated with 100 mg acarbose three times daily or placebo for 24 wk . The patients were recruited after a 4-wk screening period of dietary reinforcement . The inclusion limits for patients termed diet not satisfactory were fasting blood glucose ( FBG ) ≥ 7.8 mM and /or postpr and ial blood glucose ( BG ) ≥ 10 mM. Results FBG was lowered in the acarbose group from 9.8 to 8.4 mM and in the placebo group from 10.2 to 9.6 mM after 24 wk ( P = 0.007 vs. placebo ) . The most impressive therapeutic effect was a highly significant reduction of postpr and ial hyperglycemia for at least 5 h after the test meal ( 1-h postpr and ial BG with acarbose 10.4 mM and placebo 13.5 mM at 24 wk , P < 0.001 ) accompanied by a significant decrease in HbA1 ( acarbose 8.65 % , placebo 9.32 % , P = 0.003 ) . Whereas C-peptide and fasting serum insulin were not significantly affected by acarbose , postpr and ial insulin increment was ∼ 30 % lower after 24 wk compared with placebo . Furthermore , acarbose significantly reduced 1-h postpr and ial triglyceride levels . After an initial phase of > 4 wk ( when 76.6 % in the acarbose group vs. 28 % on placebo complained about flatulence , P < 0.001 ) , the drug was well accepted . At the end of the study , only 32 % showed mild or moderate gastrointestinal sensations . Conclusions Extrapolation shows that acarbose is an efficient and acceptable drug for the treatment of NIDDM with poor metabolic control by diet alone . It has beneficial effects on postpr and ial hyperinsulinemia and postpr and ial hypertriglyceridemia BACKGROUND Acarbose delays release of glucose from complex carbohydrates and disaccharides by inhibiting intestinal alpha-glucosidases , thereby attenuating postpr and ial increments in blood glucose and insulin . This multicenter , double-blind , placebo-controlled study compared the efficacy and safety of diet alone , acarbose , tolbutamide , and acarbose-plus-tolbutamide in non-insulin-dependent diabetes mellitus ( NIDDM ) patients . PATIENTS AND METHODS A total of 290 patients with NIDDM and fasting plasma glucose levels of at least 140 mg/dL were r and omized to receive treatment TID with acarbose 200 mg , tolbutamide 250 to 1,000 mg , a combination of both drugs , or placebo . A 6-week run-in period was followed by double-blind treatment for 24 weeks , then a 6-week follow-up period . RESULTS All active treatments were superior ( P < 0.05 ) to placebo in reducing postpr and ial hyperglycemia and HbA1c levels . The ranking in order of efficacy was : acarbose-plus-tolbutamide , tolbutamide , acarbose , and placebo . The postpr and ial reductions in glucose were approximately 85 mg/dL for acarbose-plus-tolbutamide , 71 mg/dL for tolbutamide , 56 mg/dL for acarbose , and 13 mg/dL for placebo . Tolbutamide was associated with increases in body weight and postpr and ial insulin levels when taken alone , but these were ameliorated when tolbutamide was taken in combination with acarbose . Acarbose alone or in combination with tolbutamide caused significantly more gastrointestinal adverse events ( mainly flatulence and soft stools or diarrhea ) than tolbutamide or placebo , but these were generally well tolerated . Clinical ly significant elevations in hepatic transaminase levels occurred in 3 patients in the acarbose group and 2 in the acarbose-plus-tolbutamide group . Transaminase levels returned to normal when therapy was discontinued . CONCLUSIONS Acarbose was effective and well tolerated in the treatment of NIDDM . Control of glycemia was significantly better with acarbose compared with diet alone . Acarbose-plus-tolbutamide was superior to tolbutamide alone OBJECTIVE To compare the therapeutic effects of the α-glucosidase inhibitor miglitol ( BAY m 1099 ) , the sulfonylurea glibenclamide , and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone . RESEARCH DESIGN AND METHODS After a 4-week placebo run-in period , 201 patients in 18 centers in 4 countries were r and omized in a double-blind manner to miglitol ( 50 mg t.i.d . , followed by 100 mg t.i.d . ) , glibenclamide ( 3.5 mg q.d/b.i.d . ) , or placebo for 24 weeks . Efficacy criteria were changes from baseline of HbA1c , fasting and postpr and ial blood glucose and insulin levels , body weight , and serum triglycerides . RESULTS Efficacy was assessed in 119 patients who completed the full protocol , and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis . Compared with placebo , mean baseline-adjusted HbA1c decreased by 0.75 % ( P = 0.0021 ) and 1.01 % ( P = 0.0001 ) in the miglitol and glibenclamide treatment groups , respectively . Blood glucose decreased slightly in the fasting state and considerably in the postpr and ial state in both treatment groups but not in the placebo group . Fasting insulin levels increased slightly ( NS ) in all treatment groups ; however , postpr and ial insulin levels decreased with miglitol , while increasing markedly with glibenclamide ( P = 0.0001 between all treatment groups ) . Gastrointestinal side effects ( flatulence and diarrhea ) occurred mostly in the miglitol-treated patients , while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia . CONCLUSIONS Miglitol monotherapy is effective and safe in NIDDM patients . Compared with glibenclamide , it reduced HbA1c less effectively and caused more gastrointestinal side effects . On the other h and , glibenclamide , unlike miglitol , tended to cause hypoglycemia , hyperinsulinemia , and weight gain , which are not desirable in patients with NIDDM Current therapeutic options for the treatment of non-insulin-dependent diabetes mellitus ( NIDDM ) focus on regimens that primarily lower fasting blood glucose concentrations . In several short-term studies , the alpha-glucosidase inhibitor , acarbose , has been reported to significantly lower post-pr and ial plasma glucose levels as well as HbA1c . The primary objective of this present study was to assess the long-term efficacy of adjunctive acarbose therapy to improve metabolic control . Over a 1-y period , acarbose or placebo was administered to 4 groups of patients : those managed by diet only , diet and sulfonylurea , diet and biguanide , and diet and insulin . In all treatment groups , the addition of acarbose result ed in significant reductions in postpr and ial blood glucose levels . Additionally , HbA1C was significantly lower after 12 months of acarbose therapy , compared with placebo , in all groups except the diet and insulin group . The addition of acarbose consequently exp and s the armamentarium available to clinicians for the optimization of glycemic control in patients with NIDDM Non-insulin-dependent diabetes mellitus not responding to diet only in patients with non-alcoholic liver cirrhosis is characterized by high post-pr and ial hyperglycemia . The aim of this study was to evaluate the safety and efficacy of 24 weeks of treatment with 300 mg acarbose per day in 76 consecutive out patients affected by type 2 diabetes and well-compensated liver cirrhosis . The study design was double-blind cross-over vs placebo . All patients tolerated both treatments well , and no significant variations in liver function tests were observed ( < 5 % vs pre-treatment ) . A significant reduction of several parameters was observed only after acarbose : fasting glycemia ( 19 + /- 6 vs 2 + /- 0.5 % ; p < 0.01 ) , post-pr and ial glycemia ( 41 + /- 9 vs 3 + /- 0.6 % ; p < 0.01 ) , mean glycemia ( 30 + /- 8 vs 14 + /- 5 % ; p < 0.01 ) , daily glycemic variation ( 52 + /- 8 vs 8 + /- 1 % ; p < 0.01 ) , HbA1c ( 16 + /- 1 vs 2 + /- 0.5 ; p < 0.05 ) , incremental area of C-peptide after a st and ard meal ( 80 + /- 19 vs 200 + /- 36 ng/mL/300 min ; p < 0.01 ) . After acarbose a significant increase of intestinal voiding/week ( 98 vs 28 % ; p < 0.01 ) and a parallel reduction of blood ammonia levels ( 52 + /- 9 vs 9 + /- 5 % ; p < 0.01 ) were observed . Results clearly document the good tolerability and the absence of toxic effects of acarbose on the liver , due to a theoretic absence of both absorption by the gut and hepatic metabolism of the drug . In fact , acarbose increases peristaltic movement of the gut , stimulates the proliferation of saccharolytic bacteria and simultaneously reduces proteolytic bacterial proliferation , thus actively reducing blood ammonia levels . These unexpected effects of acarbose may be used to advantage for the treatment of type 2 diabetes mellitus in patients with well-compensated liver cirrhosis The high morbidity and mortality and the increasing health care costs associated with noninsulin-dependent diabetes mellitus [ 1 - 4 ] suggest that current treatment strategies are unsatisfactory . Persisting hyperglycemia has been linked to the development of diabetic complications [ 5 ] and to the exaggeration of insulin resistance and impaired insulin secretion that characterizes the pathophysiology of noninsulin-dependent diabetes mellitus [ 6 - 9 ] . Diet therapy remains the cornerstone of the treatment strategies for noninsulin-dependent diabetes mellitus ; it is intended to achieve and maintain ideal body weight and to reverse , at least partially , the metabolic abnormalities associated with the disease [ 10 , 11 ] . Sustained weight loss , however , is rarely attained . When diet fails , oral hypoglycemic agents such as sulfonylurea or biguanide or both are added [ 12 , 13 ] . These have been shown to increase fasting plasma glucose levels , but postpr and ial hyperglycemia persists in more than 60 % of patients and probably accounts for sustained increases in hemoglobin A1c ( HbA1c ) levels [ 14 ] . Furthermore , secondary failure to oral agents is common , and more than 25 % of patients with noninsulin-dependent diabetes mellitus require insulin to achieve acceptable glycemic control [ 15 ] . Insulin therapy , however , may promote weight gain and exacerbate insulin resistance [ 15 ] . Slowly absorbable or lente carbohydrates and high-fiber diets have been proposed as ways to delay glucose absorption and thus to blunt the postpr and ial increase in plasma glucose and insulin levels [ 16 , 17 ] . Although these dietary manipulations have been shown to be effective , most patients find the regimen difficult to follow . An alternative approach to the problem of postpr and ial hyperglycemia is to use competitive inhibitors of small intestine brush-border -glucosidases such as acarbose [ 18 - 20 ] . Acarbose reduces postpr and ial plasma glucose and insulin responses [ 21 , 22 ] and may improve metabolic control in noninsulin-dependent diabetes mellitus when combined with diet alone [ 23 ] or with sulfonylurea [ 24 ] , but it was of no benefit when added to combined sulfonylurea and biguanide in one study [ 25 ] . However , most previous studies using acarbose were usually short or medium term , were often uncontrolled , and frequently had small numbers of patients [ 20 ] . No study has been done of acarbose in patients with noninsulin-dependent diabetes mellitus who were being treated with insulin . Therefore , the purpose of our study was to evaluate the long-term efficacy of acarbose in improving the metabolic control of patients with noninsulin-dependent diabetes mellitus that was not well controlled by diet alone , diet and metformin , diet and sulfonylurea , or diet and insulin . We also evaluated the safety and tolerability of acarbose during the 1-year study period ; detailed data will be reported in a separate paper ( Ross SA , Chiasson JL , Josse RG , Hunt JA , Palmason C , Rodger NW , et al. The safety of acarbose in the treatment of patients with NIDDM . A Multicenter Trial . In preparation ) , but a summary of our major findings is included in this report . Methods Patients with noninsulin-dependent diabetes mellitus of at least 6 months ' duration , the diagnosis of which was based on World Health Organization criteria [ 26 ] , were recruited from among the seven participating facilities : Camp Hill Medical Center , Halifax , Canada ; Hopital Hotel-Dieu de Montreal , Montreal Canada ; St. Michael 's Hospital , Toronto , Canada ; St. Joseph 's Hospital , London , Canada ; Walter C. Mackenzie Health Sciences Center , Edmonton , Canada ; Foothills Hospital , Calgary , Canada ; and Lion 's Gate Hospital , Vancouver , Canada . Patients were recruited from the following four treatment groups : diet alone ; diet and metformin ; diet and sulfonylurea ; and diet and insulin . Hemoglobin A1c levels at entry had to be greater than 7.0 % , except in patients treated with diet alone , whose levels had to be greater than 6.5 % . All patients had normal plasma creatinine levels and liver function test results . Patients with hypertension were included if their blood pressure was well controlled with antihypertensive medication ; patients receiving therapy with -blockers or thiazide diuretics were excluded . All patients with documented gastrointestinal disease and those taking medications likely to alter gut motility or absorption were excluded , as were patients taking medications to lower serum lipid levels . All patients were placed on a weight-maintaining diet [ 27 ] and continued to take their hypoglycemic medication . After a 6-week pretreatment period , the patients in each treatment group were r and omly assigned to receive either acarbose or placebo for 1 year . Patients were asked to take study medication with the first bite of each meal three times daily . The initial dose was 50 mg and , if necessary , was titrated upward on subsequent visits to 100 mg , and finally to a maximum of 200 mg . The dose was increased if the postpr and ial plasma glucose level was greater than 10 mmol/L and was adjusted according to the patients ' tolerance to the drug . If the postpr and ial plasma glucose level was 10 mmol/L or less , the concurrent hypoglycemic medication was decreased by approximately 25 % . Drug and dietary compliance was verified by pill counts at each visit and by 3-day recall nutritional diaries every 3 months . The efficacy values were measured before r and om selection and every 3 months throughout the study period . At those visits , fasting blood sample s were drawn for HbA1c , plasma glucose , serum C-peptide , and serum lipid profiles . The patients were then given a st and ard breakfast of Enrich ( 450 kcal ; Ross Laboratories , Montreal , Canada ) ; this liquid meal contains 55 % carbohydrates ( 61 % starch , 29 % sucrose , and 10 % soya polysaccharide ) , 30.5 % lipids , and 14.5 % proteins . Acarbose or placebo was taken with the first sip of the liquid meal . The test meal was ingested over 10 minutes , and blood sample s were drawn at 60 , 90 , and 120 minutes for plasma glucose and serum C-peptide levels . The study was approved by the institutional review board at each facility , and all patients gave informed consent . Plasma glucose levels were measured at each facility using the hexokinase method [ 28 ] ; all other values were measured in a laboratory in Toronto . The HbA1c levels were measured using the mini-column chromatography technique ( Bio-Rad Laboratories , Hercules , California ; normal range , 3.8 % to 6.3 % ) . Serum C-peptide levels were measured by radioimmunoassay [ 29 ] . Serum lipid levels were measured at the Lipid Research Laboratory at the University of Toronto , which is certified by the National Heart , Lung , and Blood Institute-Centers for Disease Control Lipid St and ardization Program [ 30 ] . Sample s were analyzed using the Technicon RA1000 and Technicon enzymatic reagents for total cholesterol ( Technicon method SM4 - 0139G86 ) , triglycerides ( Technicon method SM4 - 0173G90 ) , and triglyceride blank ( reagent no. T01 - 2013 - 01 ) ( Technicon-Miles , Mississauga , Ontario ) [ 31 ] . The high-density lipoprotein ( HDL ) cholesterol level was measured as the cholesterol in the supernatant after precipitation of the non-HDL cholesterol using dextran sulfate magnesium chloride [ 31 ] . The low-density lipoprotein ( LDL ) cholesterol level was calculated for sample s in which the triglyceride concentration was less than 4.5 mmol/L using the following formula : LDL = total cholesterol -(HDL + triglycerides)/2.2 [ 32 ] . The safety and tolerability of acarbose were assessed every 3 months throughout the study . Complete blood count and biochemistry profiles were done to check for toxicity , and possible malabsorption was assessed by measuring serum vitamins A , D , folate , and B12 and the minerals Fe , Zn , Mn , Mg , Cu , Cd , and Se . When adverse events and side effects occurred , they were documented and a question naire on symptoms was administered . Hypoglycemic reactions ( plasma glucose levels < 3.5 mmol/L ) were also documented . The results of the safety parameters will be presented in detail and discussed in a separate paper ( Ross SA , Chiasson JL , Josse RG , Hunt JA , Palmason C , Rodger NW , et al. The safety of acarbose in the treatment of patients with NIDDM . A Multicenter Trial . In preparation . ) Sample size was calculated using a two-tailed of 0.025 ( Bonferroni correction for two primary efficacy variables ) , power of 90 % ; the mean HbA1c difference was 1 % between acarbose and placebo with a st and ard deviation of 1.2 % . The four groups were treated as four separate studies . The total number of patients needed was calculated to be 76 for each treatment group : 38 for acarbose and 38 for placebo ; thus , 304 patients were needed . Allowing for an approximately 15 % dropout rate , we estimated that at least 350 patients should be enrolled . The primary analyses were comparisons of changes in HbA1c and plasma glucose values ( incremental area under the curve , or curve area ) between baseline and end of treatment . The fasting plasma glucose level was analyzed as a secondary variable . Unpaired t-tests were done to obtain P values . Patients were considered invalid for efficacy analysis if they dropped out or if they required an increase in concomitant hypoglycemic medication within 60 days of r and om assignment . The concomitant hypoglycemic medication was increased if patients became symptomatic or if fasting plasma glucose levels increased to 15 mmol/L or more . If these events occurred after 60 days , intent-to-treat analysis was done using the data from the last valid visit . The data on HbA1c and the plasma glucose curve area were also analyzed over time using repeated- measures analysis of covariance . The model included the following independent factors : treatment and facility as main effects , treatment by facility interaction and baseline values as covariates , and values at 3 , 6 , 9 , and 12 months as the dependent factors [ 33 ] . Incremental area under the curve was calculated using the trapezoidal rule after subtraction of the AIM The aim of our double-blind , placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes . METHODS We investigated 77 patients ( mean age 58.7 years , mean BMI 27.3 kg/m2 ) , treated by diet alone for at least 4 weeks . The subjects were r and omized into three treatment groups for 16 weeks : 100 mg t.i.d . acarbose ( n = 25 ) or 1 mg t.i.d . glibenclamide ( n = 27 ) or one t.i.d . placebo ( n = 25 ) . Before and after therapy , the levels of fasting plasma glucose , glycosylated haemoglobin , fasting insulin , plasma glucose and insulin 1 h after a st and ardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test . RESULTS After the treatment period , BMI in the acarbose and placebo group decreased significantly , whereas in the glibenclamide group a significant increase was observed . Fasting plasma glucose was only significant reduced under glibenclamide . The postpr and ial glucose decreased significantly after acarbose ( 13.8 vs. 11.4 mmol/l , p < 0.05 ) and glibenclamide treatment ( 14.6 vs. 11.4 mmol/l , p < 0.05 ) and was unchanged under placebo ( 13.8 vs. 13.7 mmol/l ) . The fasting insulin levels remained unchanged in all three groups , whereas postpr and ial insulin values increased significantly under glibenclamide . Neither acarbose nor glibenclamide significantly changed insulin sensitivity [ acarbose : glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin , after treatment 3.2 ; glibenclamide 2.2 vs. 2.1 ; placebo 2.6 vs. 3.0 ] . CONCLUSIONS Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which , however , was not associated with an increase of insulin sensitivity BACKGROUND Acarbose is a pseudotetrasacaride which reversibly and competitively inhibits the intestinal alpha-glycosidases leading to a decrease in the increase of postpr and ial glycemia . METHODS A multicentric double-blind clinical trial ( 8 centers ) , controlled versus placebo , crossover and r and omized was carried out in 90 non insulin dependent diabetic patients under treatment with diet or with diet and sulphonilureas . During the first three months of the trial the patients received placebo or acarbose r and omly . Following one months of wash-out with placebo the patients received the inverse medication for 3 more months . During the first month of each phase the patients received 3 x 50 mg/day of acarbose or placebo and the following 2 months 3 x 100 mg/day . RESULTS Upon comparison of the two treatments significant statistical differences were observed in HbA1 ( p = 0.0115 ) and in postpr and ial glycemia ( p = 0.0001 ) . There were differences , although not significant , in the levels of triglycerides , cholesterol , fasting glycemia , and postpr and ial insulinemia . Episodes of hypoglycemia appeared in 12 patients and 57 patients referred undesirable gastrointestinal effects . CONCLUSIONS The results of this trial indicate that acarbose may be useful in the treatment of non insulindependent diabetic patients since it significantly reduces the amount of postpr and ial glycemia and HbA1 The efficacy and safety of acarbose therapy ( 100 mg tds for 24 weeks ) was investigated in a placebo-controlled double-blind study in patients with non-insulin dependent diabetes mellitus who could not achieve satisfactory glycaemic control by diet alone . In the acarbose group , the 2 h postpr and ial blood glucose and haemoglobin A1 levels decreased significantly from 14.0 mmol l-1 to 11.3 mmol l-1 and from 11.1 % to 9.7 % , respectively . In the placebo group , the 2 h postpr and ial blood glucose ( 14.4 mmol l-1 to 14.2 mmol l-1 ) and the hemoglobin A1 level ( 10.3 % to 9.9 % ) showed no significant changes . A 75 g oral glucose tolerance test was performed before and after the study , the difference not being significant in either the acarbose group or the placebo group . The incidence of side-effects ( mainly gastrointestinal symptoms such as flatulence and abdominal distension ) was high at 78.9 % in the acarbose group and 61.1 % in the placebo group . However , there was no significant difference between the groups , and side-effects in the acarbose group tapered during the trial , suggesting that some at least were not related to the drug . From these findings , it was concluded that acarbose is an effective new treatment for diet treated non-insulin-dependent diabetic patients |
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